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177 results on '"Sennblad B"'

1. Integrative studies implicate matrix metalloproteinase‐12 as a culprit gene for large‐artery atherosclerotic stroke

Author: Mahdessian, H., Perisic Matic, L., Lengquist, M., Gertow, K., Sennblad, B., Baldassarre, D., Veglia, F., Humphries, S. E., Rauramaa, R., de Faire, U., Smit, A. J., Giral, P., Kurl, S., Mannarino, E., Tremoli, E., Hamsten, A., Eriksson, P., Hedin, U., and Mälarstig, A.
Published: 2017
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2. A phylogenetic analysis of 100 + genera and 50 + families of euasterids based on morphological and molecular data with notes on possible higher level morphological synapomorphies

Author: Bremer, K., Backlund, A., Sennblad, B., Swenson, U., Andreasen, K., Hjertson, M., Lundberg, J., Backlund, M., and Bremer, B.
Published: 2001

3. Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants

Author: Laguzzi, Federica, Maitusong, Buamina, Strawbridge, Rona J., Baldassarre, Damiano, Veglia, Fabrizio, Humphries, Steve E., Rauramaa, Rainer, Kurl, Sudhir, Smit, Andries J., Giral, Philippe, Silveira, Angela, Tremoli, Elena, Hamsten, Anders, de Faire, Ulf, Gigante, Bruna, Leander, Karin, Sirtori, C. R., Calabresi, L., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Tedesco, C., Coggi, D., Capra, N., Bonomi, A., Eriksson, P., Cooper, J., Acharya, J., Savonen, K., Huttunen, K., Rauramaa, E., Penttila, I. M., Törrönen, J., van Gessel, A. I., van Roon, A. M., Nicolai, A., Mulder, D. J., Kontush, A., Carrié, A., Gallo, A., Karppi, J., Nurmi, T., Nyyssönen, K., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Sennblad, B., Pirro, M., Vaudo, G., Siepi, D., Lupattelli, G., Mannarino, M. R., Bianconi, V., Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Karolinska Institutet [Stockholm], Xinjiang University, University of Glasgow, Università degli Studi di Milano [Milano] (UNIMI), Centro Cardiologico Monzino [Milano], Dpt di Scienze Cliniche e di Comunità [Milano] (DISCCO), Università degli Studi di Milano [Milano] (UNIMI)-Università degli Studi di Milano [Milano] (UNIMI)-Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University College of London [London] (UCL), University of Kuopio, University of Eastern Finland, University Medical Center Groningen [Groningen] (UMCG), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Multivariate analysis, Cross-sectional study, Science, [SDV]Life Sciences [q-bio], Saturated fat, Cardiology, Disease, 030204 cardiovascular system & hematology, Logistic regression, Carotid Intima-Media Thickness, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Genetics, Medicine, Humans, Genetic Predisposition to Disease, 030212 general & internal medicine, Aged, Multidisciplinary, business.industry, Middle Aged, Atherosclerosis, Dietary Fats, 3. Good health, Endocrinology, Blood pressure, Intima-media thickness, Cohort, cardiovascular system, Dietary Fats/adverse effects, Female, Atherosclerosis/epidemiology, business, Biomarkers
Abstract: The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54–79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point > zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06–1.47), CC-IMTmean (OR:1.22;1.04–1.44) and ICA-IMTmean (OR:1.26;1.07–1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis.
Published: 2021
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4. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author: Ahluwalia, T.S., Prins, B.P., Abdollahi, M., Armstrong, N.J., Aslibekyan, S., Bain, L., Jefferis, B., Baumert, J., Beekman, M., Ben-Shlomo, Y., Bis, J.C., Mitchell, B.D., Geus, E. de, Delgado, G.E., Marek, D., Eriksson, J., Kajantie, E., Kanoni, S., Kemp, J.P., Lu, C., Marioni, R.E., McLachlan, S., Milaneschi, Y., Nolte, I.M., Petrelis, A.M., Porcu, E., Sabater-Lleal, M., Naderi, E., Seppala, I., Shah, T., Singhal, G., Standl, M., Teumer, A., Thalamuthu, A., Thiering, E., Trompet, S., Ballantyne, C.M., Benjamin, E.J., Casas, J.P., Toben, C., Dedoussis, G., Deelen, J., Durda, P., Engmann, J., Feitosa, M.F., Grallert, H., Hammarstedt, A., Harris, S.E., Homuth, G., Hottenga, J.J., Jalkanen, S., Jamshidi, Y., Jawahar, M.C., Jess, T., Kivimaki, M., Kleber, M.E., Lahti, J., Liu, Y., Marques-Vidal, P., Mellstrom, D., Mooijaart, S.P., Muller-Nurasyid, M., Penninx, B., Revez, J.A., Rossing, P., Raikkonen, K., Sattar, N., Scharnagl, H., Sennblad, B., Silveira, A., St Pourcain, B., Timpson, N.J., Trollor, J., Dongen, J. van, Heemst, D. van, Visvikis-Siest, S., Vollenweider, P., Volker, U., Waldenberger, M., Willemsen, G., Zabaneh, D., Morris, R.W., Arnett, D.K., Baune, B.T., Boomsma, D.I., Chang, Y.P.C., Deary, I.J., Deloukas, P., Eriksson, J.G., Evans, D.M., Ferreira, M.A., Gaunt, T., Gudnason, V., Hamsten, A., Heinrich, J., Hingorani, A., Humphries, S.E., Jukema, J.W., Koenig, W., Kumari, M., Kutalik, Z., Lawlor, D.A., Lehtimaki, T., Marz, W., Mather, K.A., Naitza, S., Nauck, M., Ohlsson, C., Price, J.F., Raitakari, O., Rice, K., Sachdev, P.S., Slagboom, E., Sorensen, T.I.A., Spector, T., Stacey, D., Stathopoulou, M.G., Tanaka, T., Wannamethee, S.G., Whincup, P., Rotter, J.I., Dehghan, A., Boerwinkle, E., Psaty, B.M., Snieder, H., Alizadeh, B.Z., and CHARGE Inflammation Working Grp
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021

5. Genome-Wide Association Study of Circulating Interleukin 6 Levels Identifies Novel Loci

Author: Ahluwalia, TS, Prins, BP, Abdollahi, M, Armstrong, NJ, Aslibekyan, S, Bain, L, Jefferis, B, Baumert, J, Beekman, M, Ben-Shlomo, Y, Bis, JC, Mitchell, BD, de Geus, E, Delgado, GE, Marek, D, Eriksson, J, Kajantie, E, Kanoni, S, Kemp, JP, Lu, C, Marioni, RE, McLachlan, S, Milaneschi, Y, Nolte, IM, Petrelis, AM, Porcu, E, Sabater-Lleal, M, Naderi, E, Seppälä, I, Shah, T, Singhal, G, Standl, M, Teumer, A, Thalamuthu, A, Thiering, E, Trompet, S, Ballantyne, CM, Benjamin, EJ, Casas, JP, Toben, C, Dedoussis, G, Deelen, J, Durda, P, Engmann, J, Feitosa, MF, Grallert, H, Hammarstedt, A, Harris, SE, Homuth, G, Hottenga, J-J, Jalkanen, S, Jamshidi, Y, Jawahar, MC, Jess, T, Kivimaki, M, Kleber, ME, Lahti, J, Liu, Y, Marques-Vidal, P, Mellström, D, Mooijaart, SP, Müller-Nurasyid, M, Penninx, B, Revez, JA, Rossing, P, Räikkönen, K, Sattar, N, Scharnagl, H, Sennblad, B, Silveira, A, Pourcain, BS, Timpson, NJ, Trollor, J, CHARGE Inflammation Working Group, van Dongen, J, Van Heemst, D, Visvikis-Siest, S, Vollenweider, P, Völker, U, Waldenberger, M, Willemsen, G, Zabaneh, D, Morris, RW, Arnett, DK, Baune, BT, Boomsma, DI, Chang, Y-PC, Deary, IJ, Deloukas, P, Eriksson, JG, Evans, DM, Ferreira, MA, Gaunt, T, Gudnason, V, Hamsten, A, Heinrich, J, Hingorani, A, Humphries, SE, Jukema, JW, Koeing, W, Kumari, M, Kutalik, Z, Lawlor, DA, Lehtimäki, T, März, W, Mather, K, Naitza, S, Nauck, M, Ohlsson, C, Price, JF, Raitakari, O, Rice, K, Sachdev, PS, Slagboom, E, Sørensen, TIA, Spector, T, Stacey, D, Stathopoulou, MG, Tanaka, T, Wannamethee, SG, Whincup, P, Rotter, JI, Dehghan, A, Boerwinkle, E, Psaty, BM, Snieder, H, and Alizadeh, BZ
Abstract: Interleukin-6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery, and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed-effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on Chromosome (Chr) 2q14, (pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021

6. The trans-ancestral genomic architecture of glycemic traits

Author: Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), Barroso, I. (Ines), Chen, J. (Ji), Spracklen, C. N. (Cassandra N.), Marenne, G. (Gaelle), Varshney, A. (Arushi), Corbin, L. J. (Laura J.), Luan, J. (Jian'an), Willems, S. M. (Sara M.), Wu, Y. (Ying), Zhang, X. (Xiaoshuai), Horikoshi, M. (Momoko), Boutin, T. S. (Thibaud S.), Magi, R. (Reedik), Waage, J. (Johannes), Li-Gao, R. (Ruifang), Chan, K. H. (Kei Hang Katie), Yao, J. (Jie), Anasanti, M. D. (Mila D.), Chu, A. Y. (Audrey Y.), Claringbould, A. (Annique), Heikkinen, J. (Jani), Hong, J. (Jaeyoung), Hottenga, J.-J. (Jouke-Jan), Huo, S. (Shaofeng), Kaakinen, M. A. (Marika A.), Louie, T. (Tin), Maerz, W. (Winfried), Moreno-Macias, H. (Hortensia), Ndungu, A. (Anne), Nelson, S. C. (Sarah C.), Nolte, I. M. (Ilja M.), North, K. E. (Kari E.), Raulerson, C. K. (Chelsea K.), Ray, D. (Debashree), Rohde, R. (Rebecca), Rybin, D. (Denis), Schurmann, C. (Claudia), Sim, X. (Xueling), Southam, L. (Lorraine), Stewart, I. D. (Isobel D.), Wang, C. A. (Carol A.), Wang, Y. (Yujie), Wu, P. (Peitao), Zhang, W. (Weihua), Ahluwalia, T. S. (Tarunveer S.), Appel, E. V. (Emil V. R.), Bielak, L. F. (Lawrence F.), Brody, J. A. (Jennifer A.), Burtt, N. P. (Noel P.), Cabrera, C. P. (Claudia P.), Cade, B. E. (Brian E.), Chai, J. F. (Jin Fang), Chai, X. (Xiaoran), Chang, L.-C. (Li-Ching), Chen, C.-H. (Chien-Hsiun), Chen, B. H. (Brian H.), Chitrala, K. N. (Kumaraswamy Naidu), Chiu, Y.-F. (Yen-Feng), de Haan, H. G. (Hugoline G.), Delgado, G. E. (Graciela E.), Demirkan, A. (Ayse), Duan, Q. (Qing), Engmann, J. (Jorgen), Fatumo, S. A. (Segun A.), Gayan, J. (Javier), Giulianini, F. (Franco), Gong, J. H. (Jung Ho), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hartwig, F. P. (Fernando P.), He, J. (Jing), Heianza, Y. (Yoriko), Huang, T. (Tao), Huerta-Chagoya, A. (Alicia), Hwang, M. Y. (Mi Yeong), Jensen, R. A. (Richard A.), Kawaguchi, T. (Takahisa), Kentistou, K. A. (Katherine A.), Kim, Y. J. (Young Jin), Kleber, M. E. (Marcus E.), Kooner, I. K. (Ishminder K.), Lai, S. (Shuiqing), Lange, L. A. (Leslie A.), Langefeld, C. D. (Carl D.), Lauzon, M. (Marie), Li, M. (Man), Ligthart, S. (Symen), Liu, J. (Jun), Loh, M. (Marie), Long, J. (Jirong), Lyssenko, V. (Valeriya), Mangino, M. (Massimo), Marzi, C. (Carola), Montasser, M. E. (May E.), Nag, A. (Abhishek), Nakatochi, M. (Masahiro), Noce, D. (Damia), Noordam, R. (Raymond), Pistis, G. (Giorgio), Preuss, M. (Michael), Raffield, L. (Laura), Rasmussen-Torvik, L. J. (Laura J.), Rich, S. S. (Stephen S.), Robertson, N. R. (Neil R.), Rueedi, R. (Rico), Ryan, K. (Kathleen), Sanna, S. (Serena), Saxena, R. (Richa), Schraut, K. E. (Katharina E.), Sennblad, B. (Bengt), Setoh, K. (Kazuya), Smith, A. V. (Albert V.), Sparso, T. (Thomas), Strawbridge, R. J. (Rona J.), Takeuchi, F. (Fumihiko), Tan, J. (Jingyi), Trompet, S. (Stella), van den Akker, E. (Erik), van der Most, P. J. (Peter J.), Verweij, N. (Niek), Vogel, M. (Mandy), Wang, H. (Heming), Wang, C. (Chaolong), Wang, N. (Nan), Warren, H. R. (Helen R.), Wen, W. (Wanqing), Wilsgaard, T. (Tom), Wong, A. (Andrew), Wood, A. R. (Andrew R.), Xie, T. (Tian), Zafarmand, M. H. (Mohammad Hadi), Zhao, J.-H. (Jing-Hua), Zhao, W. (Wei), Amin, N. (Najaf), Arzumanyan, Z. (Zorayr), Astrup, A. (Arne), Bakker, S. J. (Stephan J. L.), Baldassarre, D. (Damiano), Beekman, M. (Marian), Bergman, R. N. (Richard N.), Bertoni, A. (Alain), Blueher, M. (Matthias), Bonnycastle, L. L. (Lori L.), Bornstein, S. R. (Stefan R.), Bowden, D. W. (Donald W.), Cai, Q. (Qiuyin), Campbell, A. (Archie), Campbell, H. (Harry), Chang, Y. C. (Yi Cheng), de Geus, E. J. (Eco J. C.), Dehghan, A. (Abbas), Du, S. (Shufa), Eiriksdottir, G. (Gudny), Farmaki, A. E. (Aliki Eleni), Franberg, M. (Mattias), Fuchsberger, C. (Christian), Gao, Y. (Yutang), Gjesing, A. P. (Anette P.), Goel, A. (Anuj), Han, S. (Sohee), Hartman, C. A. (Catharina A.), Herder, C. (Christian), Hicks, A. A. (Andrew A.), Hsieh, C.-H. (Chang-Hsun), Hsueh, W. A. (Willa A.), Ichihara, S. (Sahoko), Igase, M. (Michiya), Ikram, M. A. (M. Arfan), Johnson, W. C. (W. Craig), Jorgensen, M. E. (Marit E.), Joshi, P. K. (Peter K.), Kalyani, R. R. (Rita R.), Kandeel, F. R. (Fouad R.), Katsuya, T. (Tomohiro), Khor, C. C. (Chiea Chuen), Kiess, W. (Wieland), Kolcic, I. (Ivana), Kuulasmaa, T. (Teemu), Kuusisto, J. (Johanna), Lall, K. (Kristi), Lam, K. (Kelvin), Lawlor, D. A. (Deborah A.), Lee, N. R. (Nanette R.), Lemaitre, R. N. (Rozenn N.), Li, H. (Honglan), Lin, S.-Y. (Shih-Yi), Lindstrom, J. (Jaana), Linneberg, A. (Allan), Liu, J. (Jianjun), Lorenzo, C. (Carlos), Matsubara, T. (Tatsuaki), Matsuda, F. (Fumihiko), Mingrone, G. (Geltrude), Mooijaart, S. (Simon), Moon, S. (Sanghoon), Nabika, T. (Toru), Nadkarni, G. N. (Girish N.), Nadler, J. L. (Jerry L.), Nelis, M. (Mari), Neville, M. J. (Matt J.), Norris, J. M. (Jill M.), Ohyagi, Y. (Yasumasa), Peters, A. (Annette), Peyser, P. A. (Patricia A.), Polasek, O. (Ozren), Qi, Q. (Qibin), Raven, D. (Dennis), Reilly, D. F. (Dermot F.), Reiner, A. (Alex), Rivideneira, F. (Fernando), Roll, K. (Kathryn), Rudan, I. (Igor), Sabanayagam, C. (Charumathi), Sandow, K. (Kevin), Sattar, N. (Naveed), Schuermann, A. (Annette), Shi, J. (Jinxiu), Stringham, H. M. (Heather M.), Taylor, K. D. (Kent D.), Teslovich, T. M. (Tanya M.), Thuesen, B. (Betina), Timmers, P. R. (Paul R. H. J.), Tremoli, E. (Elena), Tsai, M. Y. (Michael Y.), Uitterlinden, A. (Andre), van Dam, R. M. (Rob M.), van Heemst, D. (Diana), van Hylckama Vlieg, A. (Astrid), van Vliet-Ostaptchouk, J. V. (Jana V.), Vangipurapu, J. (Jagadish), Vestergaard, H. (Henrik), Wang, T. (Tao), Willems van Dijk, K. (Ko), Zemunik, T. (Tatijana), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Aguilar-Salinas, C. A. (Carlos Alberto), Alarcon-Riquelme, M. E. (Marta E.), An, P. (Ping), Aviles-Santa, L. (Larissa), Becker, D. M. (Diane M.), Beilin, L. J. (Lawrence J.), Bergmann, S. (Sven), Bisgaard, H. (Hans), Black, C. (Corri), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boehm, B. O. (Bernhard O.), Bonnelykke, K. (Klaus), Boomsma, D. I. (D. I.), Bottinger, E. P. (Erwin P.), Buchanan, T. A. (Thomas A.), Canouil, M. (Mickael), Caulfield, M. J. (Mark J.), Chambers, J. C. (John C.), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Cheng, C.-Y. (Ching-Yu), Collins, F. S. (Francis S.), Correa, A. (Adolfo), Cucca, F. (Francesco), de Silva, H. J. (H. Janaka), Dedoussis, G. (George), Elmstahl, S. (Solve), Evans, M. K. (Michele K.), Ferrannini, E. (Ele), Ferrucci, L. (Luigi), Florez, J. C. (Jose C.), Franks, P. W. (Paul W.), Frayling, T. M. (Timothy M.), Froguel, P. (Philippe), Gigante, B. (Bruna), Goodarzi, M. O. (Mark O.), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grarup, N. (Niels), Grimsgaard, S. (Sameline), Groop, L. (Leif), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Hamsten, A. (Anders), Hansen, T. (Torben), Hayward, C. (Caroline), Heckbert, S. R. (Susan R.), Horta, B. L. (Bernardo L.), Huang, W. (Wei), Ingelsson, E. (Erik), James, P. S. (Pankow S.), Järvelin, M.-R. (Marjo-Ritta), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Kaleebu, P. (Pontiano), Kaplan, R. (Robert), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Keinanen-Kiukaanniemi, S. M. (Sirkka M.), Kim, B.-J. (Bong-Jo), Kivimaki, M. (Mika), Koistinen, H. A. (Heikki A.), Kooner, J. S. (Jaspal S.), Koerner, A. (Antje), Kovacs, P. (Peter), Kuh, D. (Diana), Kumari, M. (Meena), Kutalik, Z. (Zoltan), Laakso, M. (Markku), Lakka, T. A. (Timo A.), Launer, L. J. (Lenore J.), Leander, K. (Karin), Li, H. (Huaixing), Lin, X. (Xu), Lind, L. (Lars), Lindgren, C. (Cecilia), Liu, S. (Simin), Loos, R. J. (Ruth J. F.), Magnusson, P. K. (Patrik K. E.), Mahajan, A. (Anubha), Metspalu, A. (Andres), Mook-Kanamori, D. O. (Dennis O.), Mori, T. A. (Trevor A.), Munroe, P. B. (Patricia B.), Njolstad, I. (Inger), O'Connell, J. R. (Jeffrey R.), Oldehinkel, A. J. (Albertine J.), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Palmer, C. N. (Colin N. A.), Palmer, N. D. (Nicholette D.), Pedersen, O. (Oluf), Pennell, C. E. (Craig E.), Porteous, D. J. (David J.), Pramstaller, P. P. (Peter P.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Raffel, L. J. (Leslie J.), Rauramaa, R. (Rainer), Redline, S. (Susan), Ridker, P. M. (Paul M.), Rosendaal, F. R. (Frits R.), Saaristo, T. E. (Timo E.), Sandhu, M. (Manjinder), Saramies, J. (Jouko), Schneiderman, N. (Neil), Schwarz, P. (Peter), Scott, L. J. (Laura J.), Selvin, E. (Elizabeth), Sever, P. (Peter), Shu, X.-o. (Xiao-ou), Slagboom, P. E. (P. Eline), Small, K. S. (Kerrin S.), Smith, B. H. (Blair H.), Snieder, H. (Harold), Sofer, T. (Tamar), Sorensen, T. I. (Thorkild I. A.), Spector, T. D. (Tim D.), Stanton, A. (Alice), Steves, C. J. (Claire J.), Stumvoll, M. (Michael), Sun, L. (Liang), Tabara, Y. (Yasuharu), Tai, E. S. (E. Shyong), Timpson, N. J. (Nicholas J.), Tonjes, A. (Anke), Tuomilehto, J. (Jaakko), Tusie, T. (Teresa), Uusitupa, M. (Matti), van der Harst, P. (Pim), van Duijn, C. (Cornelia), Vitart, V. (Veronique), Vollenweider, P. (Peter), Vrijkotte, T. G. (Tanja G. M.), Wagenknecht, L. E. (Lynne E.), Walker, M. (Mark), Wang, Y. X. (Ya X.), Wareham, N. J. (Nick J.), Watanabe, R. M. (Richard M.), Watkins, H. (Hugh), Wei, W. B. (Wen B.), Wickremasinghe, A. R. (Ananda R.), Willemsen, G. (Gonneke), Wilson, J. F. (James F.), Wong, T.-Y. (Tien-Yin), Wu, J.-Y. (Jer-Yuarn), Xiang, A. H. (Anny H.), Yanek, L. R. (Lisa R.), Yengo, L. (Loic), Yokota, M. (Mitsuhiro), Zeggini, E. (Eleftheria), Zheng, W. (Wei), Zonderman, A. B. (Alan B.), Rotter, J. I. (Jerome I.), Gloyn, A. L. (Anna L.), McCarthy, M. I. (Mark I.), Dupuis, J. (Josee), Meigs, J. B. (James B.), Scott, R. A. (Robert A.), Prokopenko, I. (Inga), Leong, A. (Aaron), Liu, C.-T. (Ching-Ti), Parker, S. C. (Stephen C. J.), Mohlke, K. L. (Karen L.), Langenberg, C. (Claudia), Wheeler, E. (Eleanor), Morris, A. P. (Andrew P.), and Barroso, I. (Ines)
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Published: 2021

7. The trans-ancestral genomic architecture of glycemic traits

Author: Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), Tremoli E., Chen, J., Spracklen, C. N., Marenne, G., Varshney, A., Corbin, L. J., Luan, J., Willems, S. M., Wu, Y., Zhang, X., Horikoshi, M., Boutin, T. S., Magi, R., Waage, J., Li-Gao, R., Chan, K. H. K., Yao, J., Anasanti, M. D., Chu, A. Y., Claringbould, A., Heikkinen, J., Hong, J., Hottenga, J. -J., Huo, S., Kaakinen, M. A., Louie, T., Marz, W., Moreno-Macias, H., Ndungu, A., Nelson, S. C., Nolte, I. M., North, K. E., Raulerson, C. K., Ray, D., Rohde, R., Rybin, D., Schurmann, C., Sim, X., Southam, L., Stewart, I. D., Wang, C. A., Wang, Y., Wu, P., Zhang, W., Ahluwalia, T. S., Appel, E. V. R., Bielak, L. F., Brody, J. A., Burtt, N. P., Cabrera, C. P., Cade, B. E., Chai, J. F., Chai, X., Chang, L. -C., Chen, C. -H., Chen, B. H., Chitrala, K. N., Chiu, Y. -F., de Haan, H. G., Delgado, G. E., Demirkan, A., Duan, Q., Engmann, J., Fatumo, S. A., Gayan, J., Giulianini, F., Gong, J. H., Gustafsson, S., Hai, Y., Hartwig, F. P., He, J., Heianza, Y., Huang, T., Huerta-Chagoya, A., Hwang, M. Y., Jensen, R. A., Kawaguchi, T., Kentistou, K. A., Kim, Y. J., Kleber, M. E., Kooner, I. K., Lai, S., Lange, L. A., Langefeld, C. D., Lauzon, M., Li, M., Ligthart, S., Liu, J., Loh, M., Long, J., Lyssenko, V., Mangino, M., Marzi, C., Montasser, M. E., Nag, A., Nakatochi, M., Noce, D., Noordam, R., Pistis, G., Preuss, M., Raffield, L., Rasmussen-Torvik, L. J., Rich, S. S., Robertson, N. R., Rueedi, R., Ryan, K., Sanna, S., Saxena, R., Schraut, K. E., Sennblad, B., Setoh, K., Smith, A. V., Sparso, T., Strawbridge, R. J., Takeuchi, F., Tan, J., Trompet, S., van den Akker, E., van der Most, P. J., Verweij, N., Vogel, M., Wang, H., Wang, Chin Heng, Wang, N., Warren, H. R., Wen, W., Wilsgaard, T., Wong, A., Wood, A. R., Xie, T., Zafarmand, M. H., Zhao, J. -H., Zhao, W., Amin, N., Arzumanyan, Z., Astrup, A., Bakker, S. J. L., Baldassarre, D., Beekman, M., Bergman, R. N., Bertoni, Anna Marta Maria, Bluher, M., Bonnycastle, L. L., Bornstein, S. R., Bowden, D. W., Cai, Q., Campbell, A., Campbell, H., Chang, Y. C., de Geus, E. J. C., Dehghan, A., Du, S., Eiriksdottir, G., Farmaki, A. E., Franberg, M., Fuchsberger, C., Gao, Y., Gjesing, A. P., Goel, A., Han, S., Hartman, C. A., Herder, C., Hicks, A. A., Hsieh, C. -H., Hsueh, W. A., Ichihara, S., Igase, M., Ikram, M. A., Johnson, W. C., Jorgensen, M. E., Joshi, P. K., Kalyani, R. R., Kandeel, F. R., Katsuya, T., Khor, C. C., Kiess, W., Kolcic, I., Kuulasmaa, T., Kuusisto, J., Lall, K., Lam, K., Lawlor, D. A., Lee, N. R., Lemaitre, R. N., Li, H., Lin, S. -Y., Lindstrom, J., Linneberg, A., Lorenzo, C., Matsubara, T., Matsuda, F., Mingrone, Geltrude, Mooijaart, S., Moon, S., Nabika, T., Nadkarni, G. N., Nadler, J. L., Nelis, M., Neville, M. J., Norris, J. M., Ohyagi, Y., Peters, A., Peyser, P. A., Polasek, O., Qi, Q., Raven, D., Reilly, D. F., Reiner, A., Rivideneira, F., Roll, K., Rudan, I., Sabanayagam, C., Sandow, K., Sattar, N., Schurmann, A., Shi, J., Stringham, H. M., Taylor, K. D., Teslovich, T. M., Thuesen, B., Timmers, P. R. H. J., Tremoli, Elena, Tsai, M. Y., Uitterlinden, A., van Dam, R. M., van Heemst, D., van Hylckama Vlieg, A., van Vliet-Ostaptchouk, J. V., Vangipurapu, J., Vestergaard, H., Wang, T., Willems van Dijk, K., Zemunik, T., Abecasis, G. R., Adair, L. S., Aguilar-Salinas, C. A., Alarcon-Riquelme, M. E., An, P., Aviles-Santa, L., Becker, D. M., Beilin, L. J., Bergmann, S., Bisgaard, H., Black, C., Boehnke, M., Boerwinkle, E., Bohm, B. O., Bonnelykke, K., Boomsma, D. I., Bottinger, E. P., Buchanan, T. A., Canouil, M., Caulfield, M. J., Chambers, J. C., Chasman, D. I., Chen, Y. -D. I., Cheng, C. -Y., Collins, F. S., Correa, A., Cucca, F., de Silva, H. J., Dedoussis, G., Elmstahl, S., Evans, M. K., Ferrannini, E., Ferrucci, L., Florez, J. C., Franks, P. W., Frayling, T. M., Froguel, P., Gigante, B., Goodarzi, M. O., Gordon-Larsen, P., Grallert, H., Grarup, N., Grimsgaard, S., Groop, L., Gudnason, V., Guo, X., Hamsten, A., Hansen, T., Hayward, C., Heckbert, S. R., Horta, B. L., Huang, W., Ingelsson, E., James, P. S., Jarvelin, M. -R., Jonas, J. B., Jukema, J. W., Kaleebu, P., Kaplan, R., Kardia, S. L. R., Kato, N., Keinanen-Kiukaanniemi, S. M., Kim, B. -J., Kivimaki, M., Koistinen, H. A., Kooner, J. S., Korner, A., Kovacs, P., Kuh, D., Kumari, M., Kutalik, Z., Laakso, M., Lakka, T. A., Launer, L. J., Leander, K., Lin, X., Lind, L., Lindgren, C., Liu, S., Loos, R. J. F., Magnusson, P. K. E., Mahajan, A., Metspalu, A., Mook-Kanamori, D. O., Mori, T. A., Munroe, P. B., Njolstad, I., O'Connell, J. R., Oldehinkel, A. J., Ong, K. K., Padmanabhan, S., Palmer, C. N. A., Palmer, N. D., Pedersen, O., Pennell, C. E., Porteous, D. J., Pramstaller, P. P., Province, M. A., Psaty, B. M., Qi, L., Raffel, L. J., Rauramaa, R., Redline, S., Ridker, P. M., Rosendaal, F. R., Saaristo, T. E., Sandhu, M., Saramies, J., Schneiderman, N., Schwarz, P., Scott, L. J., Selvin, E., Sever, P., Shu, X. -O., Slagboom, P. E., Small, K. S., Smith, B. H., Snieder, H., Sofer, T., Sorensen, T. I. A., Spector, T. D., Stanton, A., Steves, C. J., Stumvoll, M., Sun, L., Tabara, Y., Tai, E. S., Timpson, N. J., Tonjes, A., Tuomilehto, J., Tusie, T., Uusitupa, M., van der Harst, P., van Duijn, C., Vitart, V., Vollenweider, P., Vrijkotte, T. G. M., Wagenknecht, L. E., Walker, M., Wang, Y. X., Wareham, N. J., Watanabe, R. M., Watkins, H., Wei, W. B., Wickremasinghe, A. R., Willemsen, G., Wilson, J. F., Wong, T. -Y., Wu, J. -Y., Xiang, A. H., Yanek, L. R., Yengo, L., Yokota, M., Zeggini, E., Zheng, W., Zonderman, A. B., Rotter, J. I., Gloyn, A. L., Mccarthy, M. I., Dupuis, J., Meigs, J. B., Scott, R. A., Prokopenko, I., Leong, A., Liu, C. -T., Parker, S. C. J., Mohlke, K. L., Langenberg, C., Wheeler, E., Morris, A. P., Barroso, I., van Willems van Dijk, K., Wang C., Bertoni A. (ORCID:0000-0001-7228-8718), Mingrone G. (ORCID:0000-0003-2021-528X), and Tremoli E.
Abstract: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Published: 2021

8. Bioconda: Sustainable and comprehensive software distribution for the life sciences

Author: Dale, R, Gruning, B, Sjodin, A, Rowe, J, Chapman, B, Tomkins-Tinch, C, Valieris, R, Batut, B, Caprez, A, Cokelaer, T, Yusuf, D, Beauchamp, K, Brinda, K, Wollmann, T, Corguille, G, Ryan, D, Bretaudeau, A, Hoogstrate, Y, Pedersen, B, Heeringen, S, Raden, M, Luna-Valero, S, Soranzo, N, Smet, M, Kuster, G, Kirchner, R, Pantano, L, Charlop-Powers, Z, Thornton, K, Martin, M, Beek, M, Maticzka, D, Miladi, M, Will, S, Gravouil, K, Unneberg, P, Brueffer, C, Blank, C, Piro, V, Wolff, J, Antao, T, Gladman, S, Shlyakhter, I, Hollander, M, Mabon, P, Shen, W, Boekel, J, Holtgrewe, M, Bouvier, D, de Ruiter, J, Cabral, J, Choudhary, S, Harding, N, Kleinkauf, R, Enns, E, Eggenhofer, F, Brown, J, Cock, P, Timm, H, Thomas, C, Zhang, X, Chambers, M, Turaga, N, Seiler, E, Brislawn, C, Pruesse, E, Fallmann, J, Kelleher, J, Nguyen, H, Parsons, L, Fang, Z, Stovner, E, Stoler, N, Ye, S, Wohlers, I, Farouni, R, Freeberg, M, Johnson, J, Bargull, M, Kensche, P, Webster, T, Eppley, J, Stahl, C, Rose, A, Reynolds, A, Wang, L, Garnier, X, Dirmeier, S, Knudsen, M, Taylor, J, Srivastava, A, Rai, V, Agren, R, Junge, A, Guimera, R, Khan, A, Schmeier, S, He, G, Pinello, L, Hagglund, E, Mikheyev, A, Preussner, J, Waters, N, Li, W, Capellades, J, Chande, A, Pirola, Y, Hiltemann, S, Bendall, M, Singh, S, Dunn, W, Drouin, A, Domenico, T, Bruijn, I, Larson, D, Chicco, D, Grassi, E, Gonnella, G, B, J, Giacomoni, F, Clarke, E, Blankenberg, D, Tran, C, Patro, R, Laurent, S, Gopez, M, Sennblad, B, Baaijens, J, Ewels, P, Wright, P, Enache, O, Roger, P, Dampier, W, Koppstein, D, Devisetty, U, Rausch, T, Cornwell, M, Salatino, A, Seiler, J, Jung, M, Kornobis, E, Cumbo, F, Stocker, B, Moskalenko, O, Bogema, D, Workentine, M, Newhouse, S, Leprevost, F, Arvai, K, Koster, J, Dale R., Gruning B., Sjodin A., Rowe J., Chapman B. A., Tomkins-Tinch C. H., Valieris R., Batut B., Caprez A., Cokelaer T., Yusuf D., Beauchamp K. A., Brinda K., Wollmann T., Corguille G. L., Ryan D., Bretaudeau A., Hoogstrate Y., Pedersen B. S., Heeringen S., Raden M., Luna-Valero S., Soranzo N., Smet M. D., Kuster G. V., Kirchner R., Pantano L., Charlop-Powers Z., Thornton K., Martin M., Beek M. D., Maticzka D., Miladi M., Will S., Gravouil K., Unneberg P., Brueffer C., Blank C., Piro V. C., Wolff J., Antao T., Gladman S., Shlyakhter I., Hollander M., Mabon P., Shen W., Boekel J., Holtgrewe M., Bouvier D., de Ruiter J. R., Cabral J., Choudhary S., Harding N., Kleinkauf R., Enns E., Eggenhofer F., Brown J., Cock P. J. A., Timm H., Thomas C., Zhang X. -O., Chambers M., Turaga N., Seiler E., Brislawn C., Pruesse E., Fallmann J., Kelleher J., Nguyen H., Parsons L., Fang Z., Stovner E. B., Stoler N., Ye S., Wohlers I., Farouni R., Freeberg M., Johnson J. E., Bargull M., Kensche P. R., Webster T. H., Eppley J. M., Stahl C., Rose A. S., Reynolds A., Wang L. -B., Garnier X., Dirmeier S., Knudsen M., Taylor J., Srivastava A., Rai V., Agren R., Junge A., Guimera R. V., Khan A., Schmeier S., He G., Pinello L., Hagglund E., Mikheyev A. S., Preussner J., Waters N. R., Li W., Capellades J., Chande A. T., Pirola Y., Hiltemann S., Bendall M. L., Singh S., Dunn W. A., Drouin A., Domenico T. D., Bruijn I., Larson D. E., Chicco D., Grassi E., Gonnella G., B J., Wang L., Giacomoni F., Clarke E., Blankenberg D., Tran C., Patro R., Laurent S., Gopez M., Sennblad B., Baaijens J. A., Ewels P., Wright P. R., Enache O. M., Roger P., Dampier W., Koppstein D., Devisetty U. K., Rausch T., Cornwell M., Salatino A. E., Seiler J., Jung M., Kornobis E., Cumbo F., Stocker B. K., Moskalenko O., Bogema D. R., Workentine M. L., Newhouse S. J., Leprevost F. D. V., Arvai K., Koster J., Dale, R, Gruning, B, Sjodin, A, Rowe, J, Chapman, B, Tomkins-Tinch, C, Valieris, R, Batut, B, Caprez, A, Cokelaer, T, Yusuf, D, Beauchamp, K, Brinda, K, Wollmann, T, Corguille, G, Ryan, D, Bretaudeau, A, Hoogstrate, Y, Pedersen, B, Heeringen, S, Raden, M, Luna-Valero, S, Soranzo, N, Smet, M, Kuster, G, Kirchner, R, Pantano, L, Charlop-Powers, Z, Thornton, K, Martin, M, Beek, M, Maticzka, D, Miladi, M, Will, S, Gravouil, K, Unneberg, P, Brueffer, C, Blank, C, Piro, V, Wolff, J, Antao, T, Gladman, S, Shlyakhter, I, Hollander, M, Mabon, P, Shen, W, Boekel, J, Holtgrewe, M, Bouvier, D, de Ruiter, J, Cabral, J, Choudhary, S, Harding, N, Kleinkauf, R, Enns, E, Eggenhofer, F, Brown, J, Cock, P, Timm, H, Thomas, C, Zhang, X, Chambers, M, Turaga, N, Seiler, E, Brislawn, C, Pruesse, E, Fallmann, J, Kelleher, J, Nguyen, H, Parsons, L, Fang, Z, Stovner, E, Stoler, N, Ye, S, Wohlers, I, Farouni, R, Freeberg, M, Johnson, J, Bargull, M, Kensche, P, Webster, T, Eppley, J, Stahl, C, Rose, A, Reynolds, A, Wang, L, Garnier, X, Dirmeier, S, Knudsen, M, Taylor, J, Srivastava, A, Rai, V, Agren, R, Junge, A, Guimera, R, Khan, A, Schmeier, S, He, G, Pinello, L, Hagglund, E, Mikheyev, A, Preussner, J, Waters, N, Li, W, Capellades, J, Chande, A, Pirola, Y, Hiltemann, S, Bendall, M, Singh, S, Dunn, W, Drouin, A, Domenico, T, Bruijn, I, Larson, D, Chicco, D, Grassi, E, Gonnella, G, B, J, Giacomoni, F, Clarke, E, Blankenberg, D, Tran, C, Patro, R, Laurent, S, Gopez, M, Sennblad, B, Baaijens, J, Ewels, P, Wright, P, Enache, O, Roger, P, Dampier, W, Koppstein, D, Devisetty, U, Rausch, T, Cornwell, M, Salatino, A, Seiler, J, Jung, M, Kornobis, E, Cumbo, F, Stocker, B, Moskalenko, O, Bogema, D, Workentine, M, Newhouse, S, Leprevost, F, Arvai, K, Koster, J, Dale R., Gruning B., Sjodin A., Rowe J., Chapman B. A., Tomkins-Tinch C. H., Valieris R., Batut B., Caprez A., Cokelaer T., Yusuf D., Beauchamp K. A., Brinda K., Wollmann T., Corguille G. L., Ryan D., Bretaudeau A., Hoogstrate Y., Pedersen B. S., Heeringen S., Raden M., Luna-Valero S., Soranzo N., Smet M. D., Kuster G. V., Kirchner R., Pantano L., Charlop-Powers Z., Thornton K., Martin M., Beek M. D., Maticzka D., Miladi M., Will S., Gravouil K., Unneberg P., Brueffer C., Blank C., Piro V. C., Wolff J., Antao T., Gladman S., Shlyakhter I., Hollander M., Mabon P., Shen W., Boekel J., Holtgrewe M., Bouvier D., de Ruiter J. R., Cabral J., Choudhary S., Harding N., Kleinkauf R., Enns E., Eggenhofer F., Brown J., Cock P. J. A., Timm H., Thomas C., Zhang X. -O., Chambers M., Turaga N., Seiler E., Brislawn C., Pruesse E., Fallmann J., Kelleher J., Nguyen H., Parsons L., Fang Z., Stovner E. B., Stoler N., Ye S., Wohlers I., Farouni R., Freeberg M., Johnson J. E., Bargull M., Kensche P. R., Webster T. H., Eppley J. M., Stahl C., Rose A. S., Reynolds A., Wang L. -B., Garnier X., Dirmeier S., Knudsen M., Taylor J., Srivastava A., Rai V., Agren R., Junge A., Guimera R. V., Khan A., Schmeier S., He G., Pinello L., Hagglund E., Mikheyev A. S., Preussner J., Waters N. R., Li W., Capellades J., Chande A. T., Pirola Y., Hiltemann S., Bendall M. L., Singh S., Dunn W. A., Drouin A., Domenico T. D., Bruijn I., Larson D. E., Chicco D., Grassi E., Gonnella G., B J., Wang L., Giacomoni F., Clarke E., Blankenberg D., Tran C., Patro R., Laurent S., Gopez M., Sennblad B., Baaijens J. A., Ewels P., Wright P. R., Enache O. M., Roger P., Dampier W., Koppstein D., Devisetty U. K., Rausch T., Cornwell M., Salatino A. E., Seiler J., Jung M., Kornobis E., Cumbo F., Stocker B. K., Moskalenko O., Bogema D. R., Workentine M. L., Newhouse S. J., Leprevost F. D. V., Arvai K., and Koster J.
Abstract: Bioinformatics software comes in a variety of programming languages and requires diverse installation methods. This heterogeneity makes management of a software stack complicated, error-prone, and inordinately time-consuming. Whereas software deployment has traditionally been handled by administrators, ensuring the reproducibility of data analyses1–3 requires that the researcher be able to maintain full control of the software environment, rapidly modify it without administrative privileges, and reproduce the same software stack on different machines.
Published: 2018

9. Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study

Author: Bonomi, A., Veglia, F., Baldassarre, D., Strawbridge, R. J., Golabkesh, Z., Sennblad, B., Leander, K., Smit, A. J., Giral, P., Humphries, S. E., Tremoli, E., Hamsten, A., de Faire, U., Gigante, B., Sirtori, C. R., Castelnuovo, S., Calabresi, L., Amato, M., Frigerio, B., Ravani, A., Sansaro, D., Coggi, D., Tedesco, C. C., Eriksson, P., Silveira, A., Laguzzi, F., Cooper, J., Acharya, J., Huttunen, K., Rauramaa, E., Pekkarinen, H., Penttila, I. M., Torronen, J., Rauramaa, R., van Gessel, A. I., van Roon, A. M., Teune, G. C., Kuipers, W. D., Bruin, M., Nicolai, A., Haarsma-Jorritsma, P., Mulder, D. J., Bilo, H. J. G., Smeets, G. H., Beaudeux, J. L., Kahn, J. F., Carreau, V., Kontush, A., Karppi, J., Nurmi, T., Nyyssonen, K., Salonen, R., Tuomainen, T. P., Tuomainen, J., Kauhanen, J., Kurl, S., Vaudo, G., Alaeddin, A., Siepi, D., Lupattelli, G., Mannarino, E., Groningen Kidney Center (GKC), Lifestyle Medicine (LM), and Translational Immunology Groningen (TRIGR)
Subjects: Male, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Article, Gene Frequency, Risk Factors, Cytokine Receptor gp130, Humans, Genetic Predisposition to Disease, POPULATION, Aged, Medicinsk genetik, RISK, VASCULAR EVENTS, Interleukin-6, GENOME-WIDE, Genetic Variation, SIGNAL TRANSDUCER GP130, Middle Aged, Atherosclerosis, POLYMORPHISM, Genetic Loci, INTERLEUKIN-6 RECEPTOR, SOLUBLE GP130, Cytokines, Female, Medical Genetics, 4 SUBUNITS, Biomarkers
Abstract: The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 × 10−5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (β = 0.03 SE = 0.007, p = 4.77 × 10−5) and inversely associated with c-IMT (c-IMTmean–max β = −0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.
Published: 2020

10. A phylogenetic analysis of 100+ genera and 50+ families of euasterids based on morphological and molecular data with notes on possible higher level morphological synapomorphies

Author: Bremer, K., Backlund, A., Sennblad, B., Swenson, U., Andreasen, K., Hjertson, M., Lundberg, J., Backlund, M., and Bremer, B.
Published: 2001
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11. Bioconda: sustainable and comprehensive software distribution for the life sciences

Author: Dale R., Gruning B., Sjodin A., Rowe J., Chapman B. A., Tomkins-Tinch C. H., Valieris R., Batut B., Caprez A., Cokelaer T., Yusuf D., Beauchamp K. A., Brinda K., Wollmann T., Corguille G. L., Ryan D., Bretaudeau A., Hoogstrate Y., Pedersen B. S., Heeringen S., Raden M., Luna-Valero S., Soranzo N., Smet M. D., Kuster G. V., Kirchner R., Pantano L., Charlop-Powers Z., Thornton K., Martin M., Beek M. D., Maticzka D., Miladi M., Will S., Gravouil K., Unneberg P., Brueffer C., Blank C., Piro V. C., Wolff J., Antao T., Gladman S., Shlyakhter I., Hollander M., Mabon P., Shen W., Boekel J., Holtgrewe M., Bouvier D., de Ruiter J. R., Cabral J., Choudhary S., Harding N., Kleinkauf R., Enns E., Eggenhofer F., Brown J., Cock P. J. A., Timm H., Thomas C., Zhang X. -O., Chambers M., Turaga N., Seiler E., Brislawn C., Pruesse E., Fallmann J., Kelleher J., Nguyen H., Parsons L., Fang Z., Stovner E. B., Stoler N., Ye S., Wohlers I., Farouni R., Freeberg M., Johnson J. E., Bargull M., Kensche P. R., Webster T. H., Eppley J. M., Stahl C., Rose A. S., Reynolds A., Wang L. -B., Garnier X., Dirmeier S., Knudsen M., Taylor J., Srivastava A., Rai V., Agren R., Junge A., Guimera R. V., Khan A., Schmeier S., He G., Pinello L., Hagglund E., Mikheyev A. S., Preussner J., Waters N. R., Li W., Capellades J., Chande A. T., Pirola Y., Hiltemann S., Bendall M. L., Singh S., Dunn W. A., Drouin A., Domenico T. D., Bruijn I., Larson D. E., Chicco D., Grassi E., Gonnella G., B J., Wang L., Giacomoni F., Clarke E., Blankenberg D., Tran C., Patro R., Laurent S., Gopez M., Sennblad B., Baaijens J. A., Ewels P., Wright P. R., Enache O. M., Roger P., Dampier W., Koppstein D., Devisetty U. K., Rausch T., Cornwell M., Salatino A. E., Seiler J., Jung M., Kornobis E., Cumbo F., Stocker B. K., Moskalenko O., Bogema D. R., Workentine M. L., Newhouse S. J., Leprevost F. D. V., Arvai K., Koster J., Albert-Ludwigs-Universität Freiburg, National Institutes of Health [Bethesda] (NIH), Swedish Defence Research Agency [Stockholm] (FOI), Umeå University, Harvard T.H. Chan School of Public Health, New York University [Abu Dhabi], NYU System (NYU), Harvard University [Cambridge], Hospital Camargo Sao Paulo, Partenaires INRAE, University of Duisburg-Essen, This work was supported by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health (R.D.), the Netherlands Organisation for Scientific Research (NWO) (VENI grant 016.Veni.173.076 to J.K.), the German Research Foundation (SFB 876 to J.K.), and the NYU Abu Dhabi Research Institute for the NYU Abu Dhabi Center for Genomics and Systems Biology, program number CGSB1 (grant to J.R. and A. Yousif)., We thank all contributors, the conda-forge team, and Anaconda Inc. for excellent cooperation. Further, we thank Travis CI (https://travis-ci.com) and Circle CI (https://circleci.com) for providing free Linux and macOS computing capacity. Finally, we thank ELIXIR (https://www.elixir-europe.org) for constant support and donation of staff., Etienne Kornobis (Epigenetic Regulation Unit, Institut Pasteur, Paris, France) fait partie de Bioconda Team, Bioinformatics Group, Department of Computer Science, University of Freiburg [Freiburg], Laboratory of Cellular and Developmental Biology (LCDB), NIDDK, NIH, Department of Organismic and Evolutionary Biology, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Microbiologie Environnement Digestif Santé (MEDIS), INRA Clermont-Ferrand-Theix-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Umea Plant Science Center (UPSC), Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences (SLU)-Swedish University of Agricultural Sciences (SLU), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Harvard University, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Dale, R, Gruning, B, Sjodin, A, Rowe, J, Chapman, B, Tomkins-Tinch, C, Valieris, R, Batut, B, Caprez, A, Cokelaer, T, Yusuf, D, Beauchamp, K, Brinda, K, Wollmann, T, Corguille, G, Ryan, D, Bretaudeau, A, Hoogstrate, Y, Pedersen, B, Heeringen, S, Raden, M, Luna-Valero, S, Soranzo, N, Smet, M, Kuster, G, Kirchner, R, Pantano, L, Charlop-Powers, Z, Thornton, K, Martin, M, Beek, M, Maticzka, D, Miladi, M, Will, S, Gravouil, K, Unneberg, P, Brueffer, C, Blank, C, Piro, V, Wolff, J, Antao, T, Gladman, S, Shlyakhter, I, Hollander, M, Mabon, P, Shen, W, Boekel, J, Holtgrewe, M, Bouvier, D, de Ruiter, J, Cabral, J, Choudhary, S, Harding, N, Kleinkauf, R, Enns, E, Eggenhofer, F, Brown, J, Cock, P, Timm, H, Thomas, C, Zhang, X, Chambers, M, Turaga, N, Seiler, E, Brislawn, C, Pruesse, E, Fallmann, J, Kelleher, J, Nguyen, H, Parsons, L, Fang, Z, Stovner, E, Stoler, N, Ye, S, Wohlers, I, Farouni, R, Freeberg, M, Johnson, J, Bargull, M, Kensche, P, Webster, T, Eppley, J, Stahl, C, Rose, A, Reynolds, A, Wang, L, Garnier, X, Dirmeier, S, Knudsen, M, Taylor, J, Srivastava, A, Rai, V, Agren, R, Junge, A, Guimera, R, Khan, A, Schmeier, S, He, G, Pinello, L, Hagglund, E, Mikheyev, A, Preussner, J, Waters, N, Li, W, Capellades, J, Chande, A, Pirola, Y, Hiltemann, S, Bendall, M, Singh, S, Dunn, W, Drouin, A, Domenico, T, Bruijn, I, Larson, D, Chicco, D, Grassi, E, Gonnella, G, B, J, Giacomoni, F, Clarke, E, Blankenberg, D, Tran, C, Patro, R, Laurent, S, Gopez, M, Sennblad, B, Baaijens, J, Ewels, P, Wright, P, Enache, O, Roger, P, Dampier, W, Koppstein, D, Devisetty, U, Rausch, T, Cornwell, M, Salatino, A, Seiler, J, Jung, M, Kornobis, E, Cumbo, F, Stocker, B, Moskalenko, O, Bogema, D, Workentine, M, Newhouse, S, Leprevost, F, Arvai, K, Koster, J, Urology, and Pathology
Subjects: 0301 basic medicine, Computer science, [SDV]Life Sciences [q-bio], Medizin, computer.software_genre, Biochemistry, User-Computer Interface, 03 medical and health sciences, 0302 clinical medicine, Software system, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Social software engineering, Database, business.industry, Software development, INF/01 - INFORMATICA, Computational Biology, Cell Biology, Software distribution, 030104 developmental biology, Software construction, [SDE]Environmental Sciences, Package development process, Backporting, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, computer, Software, 030217 neurology & neurosurgery, Biotechnology
Abstract: International audience; We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi- platform and language-agnostic package manager Conda. Currently, Bioconda o ers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bio- conda improves analysis reproducibility by allowing users to de ne isolated environments with de ned software versions, all of which are easily installed and managed without administrative privileges.
Published: 2018
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12. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps (Nature Genetics, (2016), 48, 11, (1303-1312), 10.1038/ng.3668)

Author: Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., Soranzo, N., Iotchkova, V., Huang, J., Morris, J. A., Jain, D., Barbieri, C., Ukovich, Walter, Min, J. L., Chen, L., Astle, W., Cocca, M., Deelen, P., Elding, H., Farmaki, A. -E., Franklin, C. S., Franberg, M., Gaunt, T. R., Hofman, A., Jiang, T., Kleber, M. E., Lachance, G., Luan, J., Malerba, G., Matchan, A., Mead, D., Memari, Y., Ntalla, I., Panoutsopoulou, K., Pazoki, R., Perry, J. R. B., Rivadeneira, F., Sabater-Lleal, M., Sennblad, B., Shin, S. -Y., Southam, L., Traglia, M., van Dijk, F., van Leeuwen, E. M., Zaza, G., Zhang, W., Amin, N., Butterworth, A., Chambers, J. C., Dedoussis, G., Dehghan, A., Franco, O. H., Franke, L., Frontini, M., Gambaro, G., Gasparini, P., Hamsten, A., Isaacs, A., Kooner, J. S., Kooperberg, C., Langenberg, C., Marz, W., Scott, R. A., Swertz, M. A., Toniolo, D., Uitterlinden, A. G., van Duijn, C. M., Watkins, H., Zeggini, E., Maurano, M. T., Timpson, N. J., Reiner, A. P., Auer, P. L., and Soranzo, N.
Subjects: Author correction
Abstract: In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.
Published: 2018

13. Nat Commun

Author: Franceschini, N., GIAMBARTOLOMEI, C., DE VRIES, P. S., FINAN, C., BIS, J. C., HUNTLEY, R. P., LOVERING, R. C., TAJUDDIN, S. M., WINKLER, T. W., GRAFF, M., KAVOUSI, M., Dale, C., SMITH, A. V., Hofer, E., VAN LEEUWEN, E. M., Nolte, I. M., Lu, L., Scholz, M., Sargurupremraj, Muralidharan, PITKANEN, N., FRANZEN, O., Joshi, P. K., NOORDAM, R., MARIONI, R. E., Hwang, S. J., MUSANI, S. K., SCHMINKE, U., PALMAS, W., ISAACS, A., CORREA, A., ZONDERMAN, A. B., Hofman, A., TEUMER, A., COX, A. J., UITTERLINDEN, A. G., Wong, A., SMIT, A. J., NEWMAN, A. B., Britton, A., RUUSALEPP, A., Sennblad, B., HEDBLAD, B., PASANIUC, B., PENNINX, B. W., LANGEFELD, C. D., WASSEL, C. L., Tzourio, Christophe, Fava, C., BALDASSARRE, D., O'LEARY, D. H., TEUPSER, D., Kuh, D., TREMOLI, E., MANNARINO, E., Grossi, E., BOERWINKLE, E., SCHADT, E. E., INGELSSON, E., VEGLIA, F., Rivadeneira, F., BEUTNER, F., Chauhan, Ganesh, Heiss, G., SNIEDER, H., Campbell, H., VOLZKE, H., MARKUS, H. S., DEARY, I. J., JUKEMA, J. W., de Graaf, J., Price, J., POTT, J., HOPEWELL, J. C., Liang, J., Thiery, J., Engmann, J., GERTOW, K., Rice, K., TAYLOR, K. D., DHANA, K., KIEMENEY, Lalm, LIND, L., RAFFIELD, L. M., LAUNER, L. J., HOLDT, L. M., DORR, M., DICHGANS, M., TRAYLOR, M., SITZER, M., KUMARI, M., Kivimaki, M., Nalls, M. A., MELANDER, O., RAITAKARI, O., FRANCO, O. H., RUEDA-OCHOA, O. L., ROUSSOS, P., WHINCUP, P. H., Amouyel, P., Giral, P., ANUGU, P., WONG, Q., Malik, R., RAURAMAA, R., BURKHARDT, R., Hardy, R., Schmidt, R., DE MUTSERT, R., MORRIS, R. W., STRAWBRIDGE, R. J., WANNAMETHEE, S. G., HAGG, S., Shah, S., MCLACHLAN, S., TROMPET, S., SESHADRI, S., KURL, S., HECKBERT, S. R., Ring, S., HARRIS, T. B., LEHTIMAKI, T., GALESLOOT, T. E., Shah, T., DE FAIRE, U., Plagnol, V., ROSAMOND, W. D., Post, W., Zhu, X., Zhang, X., Guo, X., SABA, Y., DEHGHAN, A., SELDENRIJK, A., MORRISON, A. C., HAMSTEN, A., PSATY, B. M., VAN DUIJN, C. M., LAWLOR, D. A., MOOK-KANAMORI, D. O., BOWDEN, D. W., Schmidt, H., WILSON, J. F., ROTTER, J. I., WARDLAW, J. M., DEANFIELD, J., HALCOX, J., LYYTIKAINEN, L. P., Loeffler, M., EVANS, M. K., Debette, Stéphanie, HUMPHRIES, S. E., VOLKER, U., GUDNASON, V., HINGORANI, A. D., BJORKEGREN, J. L. M., CASAS, J. P., O'DONNELL, C. J., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: VINTAGE, cardiovascular system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, cardiovascular diseases, HEALTHY
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
Full Text: View/download PDF

14. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N, Giambartolomei, C, de Vries, PS, Finan, C, Bis, JC, Huntley, RP, Lovering, RC, Tajuddin, SM, Winkler, TW, Graff, M, Kavousi, M, Dale, C, Smith, AV, Hofer, E, van Leeuwen, EM, Nolte, IM, Lu, L, Scholz, M, Sargurupremraj, M, Pitkänen, N, Franzén, O, Joshi, PK, Noordam, R, Marioni, RE, Hwang, SJ, Musani, SK, Schminke, U, Palmas, W, Isaacs, A, Correa, A, Zonderman, AB, Hofman, A, Teumer, A, Cox, AJ, Uitterlinden, AG, Wong, A, Smit, AJ, Newman, AB, Britton, A, Ruusalepp, A, Sennblad, B, Hedblad, B, Pasaniuc, B, Penninx, BW, Langefeld, CD, Wassel, CL, Tzourio, C, Fava, C, Baldassarre, D, O’Leary, DH, Teupser, D, Kuh, D, Tremoli, E, Mannarino, E, Grossi, E, Boerwinkle, E, Schadt, EE, Ingelsson, E, Veglia, F, Rivadeneira, F, Beutner, F, Chauhan, G, Heiss, G, Snieder, H, Campbell, H, Völzke, H, Markus, HS, Deary, IJ, Jukema, JW, de Graaf, J, Price, J, Pott, J, Hopewell, JC, Liang, J, Thiery, J, Engmann, J, Gertow, K, Rice, K, Taylor, KD, Dhana, K, Kiemeney, LALM, Lind, L, Raffield, LM, Launer, LJ, Holdt, LM, Dörr, M, Dichgans, M, Traylor, M, Sitzer, M, Kumari, M, Kivimaki, M, Nalls, MA, Melander, O, Raitakari, O, Franco, OH, Rueda-Ochoa, OL, Roussos, P, Whincup, PH, Amouyel, P, and Giral, P
Subjects: Aging, MEGASTROKE Consortium, Quantitative Trait Loci, ADAMTS9 Protein, Coronary Disease, Cardiovascular, Polymorphism, Single Nucleotide, Carotid Intima-Media Thickness, Protein-Lysine 6-Oxidase, Risk Factors, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Aetiology, Polymorphism, Heart Disease - Coronary Heart Disease, Plaque, Atherosclerotic, Human Genome, Single Nucleotide, Atherosclerosis, Plaque, Atherosclerotic, Brain Disorders, Stroke, Heart Disease, cardiovascular system, Amino Acid Oxidoreductases, Lod Score, Genome-Wide Association Study
Abstract: © 2018, The Author(s). Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018

15. Associations of autozygosity with a broad range of human phenotypes

Author: Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), Wilson, J.F. (James), Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), and Wilson, J.F. (James)
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
Published: 2019
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16. Associations of autozygosity with a broad range of human phenotypes

Author: Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), Wilson, J. F. (James F.), Clark, D. W. (David W.), Okada, Y. (Yukinori), Moore, K. H. (Kristjan H. S.), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C. L. (Catriona L. K.), Lin, K. (Kuang), Zhao, J. H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T. M. (Traci M.), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M. J. (Matthew J.), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D. L. (Diana L.), Dekker, A. M. (Annelot M.), Eccles, D. A. (David A.), Van Eijk, K. R. (Kristel R.), Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S. D. (Scott D.), de Haan, H. G. (Hugoline G.), Harris, S. E. (Sarah E.), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. E. (Iris E.), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M. E. (Marcus E.), Li, S. A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M. E. (May E.), van der Most, P. J. (Peter J.), Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R. B. (Rashmi B.), Priyanka, T. D. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B. R. (Bishwa R.), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M. C. (Melissa C.), Smith, A. V. (Albert Vernon), van der Spek, A. (Ashley), Spracklen, C. N. (Cassandra N.), Strawbridge, R. J. (Rona J.), Tajuddin, S. M. (Salman M.), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. R. (Helen R.), Wootton, R. E. (Robyn E.), Yanek, L. R. (Lisa R.), Yao, J. (Jie), Yousri, N. A. (Noha A.), Zhao, W. (Wei), Adeyemo, A. A. (Adebowale A.), Afaq, S. (Saima), Alberto Aguilar-Salinas, C. (Carlos), Akiyama, M. (Masato), Albert, M. L. (Matthew L.), Allison, M. A. (Matthew A.), Alver, M. (Maris), Aung, T. (Tin), Azizi, F. (Fereidoun), Bentley, A. R. (Amy R.), Boeing, H. (Heiner), Boerwinkle, E. (Eric), Borja, J. B. (Judith B.), de Borst, G. J. (Gert J.), Bottinger, E. P. (Erwin P.), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y. I. (Yii-Der I.), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F. S. (Francis S.), Concas, M. P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Van Dam, R. M. (Rob M.), Damulina, A. (Anna), Daneshpour, M. S. (Maryam S.), Day, F. R. (Felix R.), Delgado, G. E. (Graciela E.), Dhana, K. (Klodian), Doney, A. S. (Alexander S. F.), Doerr, M. (Marcus), Doumatey, A. P. (Ayo P.), Dzimiri, N. (Nduna), Ebenesersdottir, S. S. (S. Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J. F. (Janine F.), Fischer, K. (Krista), Freedman, B. I. (Barry I.), Girotto, G. (Giorgia), Goel, A. (Anuj), Gogele, M. (Martin), Goodarzi, M. O. (Mark O.), Graff, M. (Mariaelisa), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D. F. (Daniel F.), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S. P. (Saskia P.), Haiman, C. A. (Christopher A.), Halevy, A. (Avner), Harris, T. B. (Tamara B.), Hedayati, M. (Mehdi), van Heel, D. A. (David A.), Hirata, M. (Makoto), Hofer, I. (Imo), Hsiung, C. A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M. A. (M. Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N. D. (Nicola D.), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C. C. (Chiea Chuen), de Kleijn, D. P. (Dominique P. V.), Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Kramer, B. K. (Bernhard K.), Kutalik, Z. (Zoltan), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Lawlor, D. A. (Deborah A.), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. M. (Markus M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S. J. (Stephanie J.), Loomis, S. (Stephanie), Lu, Y. (Yingchang), Luan, J. (Jian'an), Magi, R. (Reedik), Manichaikul, A. W. (Ani W.), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X. W. (Xue W.), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I. Y. (Iona Y.), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (Pierre-Emmanuel), Moreno-Macias, H. (Hortensia), Mori, T. A. (Trevor A.), Morrison, A. C. (Alanna C.), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A. D. (Alison D.), de Mutsert, R. (Renee), Mychaleckyj, J. C. (Josyf C.), Nalls, M. A. (Mike A.), Nauck, M. (Matthias), Neville, M. J. (Matt J.), Nolte, I. M. (Ilja M.), Ong, K. K. (Ken K.), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Palsson, G. (Gunnar), Pankow, J. S. (James S.), Pattaro, C. (Cristian), Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N. (Neil), Pramstaller, P. P. (Peter P.), Quintana-Murci, L. (Lluis), Raikkonen, K. (Katri), Ralhan, S. (Sarju), Rao, D. C. (Dabeeru C.), van Rheenen, W. (Wouter), Rich, S. S. (Stephen S.), Ridker, P. M. (Paul M.), Rietveld, C. A. (Cornelius A.), Robino, A. (Antonietta), van Rooij, F. J. (Frank J. A.), Ruggiero, D. (Daniela), Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Felicita Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L. J. (Laura J.), Scott, W. R. (William R.), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), van Setten, J. (Jessica), Sever, P. J. (Peter J.), Sheu, W. H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S. R. (Sharvari Rahul), Sigurdsson, J. K. (Jon K.), Sikka, T. T. (Timo Tonis), Singh, J. R. (Jai Rup), Smith, B. H. (Blair H.), Stancakova, A. (Alena), Stanton, A. (Alice), Starr, J. M. (John M.), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M. A. (Morris A.), Taylor, A. M. (Adele M.), Taylor, K. D. (Kent D.), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R. P. (Russell P.), Tusie-Luna, T. (Teresa), Tzoulaki, I. (Ioanna), Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J. H. (Jan H.), Vitart, V. (Veronique), Volker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S. M. (Salma M.), Waldenberger, M. (Melanie), Wander, G. S. (Gurpreet S.), Wang, Y. X. (Ya Xing), Wareham, N. J. (Nicholas J.), Wild, S. (Sarah), Yajnik, C. S. (Chittaranjan S.), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F. W. (Folkert W.), Bakker, S. J. (Stephan J. L.), Becker, D. M. (Diane M.), Lehne, B. (Benjamin), Bennett, D. A. (David A.), van den Berg, L. H. (Leonard H.), Berndt, S. I. (Sonja I.), Bharadwaj, D. (Dwaipayan), Bielak, L. F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Mike), Bouchard, C. (Claude), Bradfield, J. P. (Jonathan P.), Brody, J. A. (Jennifer A.), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. J. (Mark J.), Cesarini, D. (David), Chambers, J. C. (John C.), Chandak, G. R. (Giriraj Ratan), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Cornelis, M. (Marilyn), Cusi, D. (Daniele), Smith, G. D. (George Davey), Deary, I. J. (Ian J.), Dorajoo, R. (Rajkumar), van Duijn, C. M. (Cornelia M.), Ellinghaus, D. (David), Erdmann, J. (Jeanette), Eriksson, J. G. (Johan G.), Evangelou, E. (Evangelos), Evans, M. K. (Michele K.), Faul, J. D. (Jessica D.), Feenstra, B. (Bjarke), Feitosa, M. (Mary), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S. F. (Struan F. A.), Griffiths, L. R. (Lyn R.), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), van der Harst, P. (Pim), Heng, C.-K. (Chew-Kiat), Hicks, A. A. (Andrew A.), Hochner, H. (Hagit), Huikuri, H. (Heikki), Hunt, S. C. (Steven C.), Jaddoe, V. W. (Vincent W. V.), De Jager, P. L. (Philip L.), Johannesson, M. (Magnus), Johansson, A. (Asa), Jonas, J. B. (Jost B.), Jukema, J. W. (J. Wouter), Junttila, J. (Juhani), Kaprio, J. (Jaakko), Kardia, S. L. (Sharon L. R.), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S. W. (Sander W.), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R. A. (Rodney A.), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N. G. (Nicholas G.), Marz, W. (Winfried), Matullo, G. (Giuseppe), McCarthy, M. I. (Mark I.), Medland, S. E. (Sarah E.), Merriman, T. R. (Tony R.), Metspalu, A. (Andres), Meyer, B. F. (Brian F.), Mohlke, K. L. (Karen L.), Montgomery, G. W. (Grant W.), Mook-Kanamori, D. (Dennis), Munroe, P. B. (Patricia B.), North, K. E. (Kari E.), Nyholt, D. R. (Dale R.), O'connell, J. R. (Jeffery R.), Ober, C. (Carole), Oldehinkel, A. J. (Albertine J.), Palmas, W. (Walter), Palmer, C. (Colin), Pasterkamp, G. G. (Gerard G.), Patin, E. (Etienne), Pennell, C. E. (Craig E.), Perusse, L. (Louis), Peyser, P. A. (Patricia A.), Pirastu, M. (Mario), Polderman, T. J. (Tinca J. C.), Porteous, D. J. (David J.), Posthuma, D. (Danielle), Psaty, B. M. (Bruce M.), Rioux, J. D. (John D.), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J. I. (Jerome I.), Rudan, I. (Igor), Den Ruijter, H. M. (Hester M.), Sanghera, D. K. (Dharambir K.), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M. B. (Matthias B.), Schunkert, H. (Heribert), Scott, R. A. (Robert A.), Shuldiner, A. R. (Alan R.), Sim, X. (Xueling), Small, N. (Neil), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N. J. (Nicholas J.), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C. A. (Carol A.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B. S. (Babette S.), Zonderman, A. B. (Alan B.), Perola, M. (Markus), Magnusson, P. K. (Patrik K. E.), Uitterlinden, A. G. (Andre G.), Kooner, J. S. (Jaspal S.), Chasman, D. I. (Daniel I.), Loos, R. J. (Ruth J. F.), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. S. (Chris S.), Hayward, C. (Caroline), Walters, R. G. (Robin G.), Perry, J. R. (John R. B.), Esko, T. (Tonu), Helgason, A. (Agnar), Stefansson, K. (Kari), Joshi, P. K. (Peter K.), Kubo, M. (Michiaki), and Wilson, J. F. (James F.)
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
Published: 2019

17. Erratum to: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author: Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jie), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimilian), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J., Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John R B), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A. (Adam), Chambers, J.C. (John C), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Isaacs, A.J. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A.P. (Alexander P), Auer, P.L. (Paul L), and Soranzo, N. (Nicole)
Abstract: In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.
Published: 2018
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18. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), Morris, R.W. (Richard), Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), and Morris, R.W. (Richard)
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
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19. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, 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Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

20. Genetic studies of body mass index yield new insights for obesity biology

Author: Locke, A, Kahali, B, Berndt, S, Justice, A, Pers, T, Day, F, Powell, C, Vedantam, S, Buchkovich, M, Yang, J, Croteau-Chonka, D, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J, Magi, R, Randall, J, Winkler, T, Wood, A, Workalemahu, T, Faul, J, Smith, J, Zhao, J, Zhao, W, Chen, J, Fehrmann, R, Hedman, A, Karjalainen, J, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bolton, J, Bragg-Gresham, J, Buyske, S, Demirkan, A, Deng, G, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Goel, A, Gong, J, Jackson, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Leach, I, Medina-Gomez, C, Medland, S, Nalls, M, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Shungin, D, Stancakova, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet-Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Isaacs, A, Albrecht, E, Arnlov, J, Arscott, G, Attwood, A, Bandinelli, S, Barrett, A, Bas, I, Bellis, C, Bennett, A, Berne, C, Blagieva, R, Bluher, M, Bohringer, S, Bonnycastle, L, Bottcher, Y, Boyd, H, Bruinenberg, M, Caspersen, I, Chen, Y, Clarke, R, Daw, E, de Craen, A, Delgado, G, Dimitriou, M, Doney, A, Eklund, N, Estrada, K, Eury, E, Folkersen, L, Fraser, R, Garcia, M, Geller, F, Giedraitis, V, Gigante, B, Go, A, Golay, A, Goodall, A, Gordon, S, Gorski, M, Grabe, H, Grallert, H, Grammer, T, Grassler, J, Gronberg, H, Groves, C, Gusto, G, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heard-Costa, N, Helmer, Q, Hengstenberg, C, Holmen, O, Hottenga, J, James, A, Jeff, J, Johansson, A, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindstrom, J, Lo, K, Lobbens, S, Lorbeer, R, Lu, Y, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Mclachlan, S, Menni, C, Merger, S, Mihailov, E, Milani, L, Moayyeri, A, Monda, K, Morken, M, Mulas, A, Muller, G, 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Abstract: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Published: 2015

21. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author: Strawbridge, R.J., Silveira, A., Hoed, M. den, Gustafsson, S., Luan, J.A., Rybin, D., Dupuis, J., Li-Gao, R.F., Kavousi, M., Dehghan, A., Haljas, K., Lahti, J., Gadin, J.R., Backlund, A., Faire, U. de, Gertow, K., Giral, P., Goel, A., Humphries, S.E., Kurl, S., Langenberg, C., Lannfelt, L.L., Lind, L., Lindgren, C.C.M., Mannarino, E., Mook-Kanamori, D.O., Morris, A.P., Mutsert, R. de, Rauramaa, R., Saliba-Gustafsson, P., Sennblad, B., Smit, A.J., Syvanen, A.C., Tremoli, E., Veglia, F., Zethelius, B., Bjorck, H.M., Eriksson, J.G., Hofman, A., Franco, O.H., Watkins, H., Jukema, J.W., Florez, J.C., Wareham, N.J., Meigs, J.B., Ingelsson, E., Baldassarre, D., Hamsten, A., IMPROVE Study Grp, Medicum, Department of Psychology and Logopedics, University of Helsinki, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Developmental Psychology Research Group, Luan, Jian'an [0000-0003-3137-6337], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Carotid Artery Diseases, Male, EXPRESSION, endocrine system, Genetic variants, endocrine system diseases, Quantitative Trait Loci, PATHOPHYSIOLOGY, DEPENDENT DIABETES-MELLITUS, Vascular Remodeling, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Gene Frequency, Risk Factors, Intima-media-thickness, Humans, Genetic Predisposition to Disease, CORONARY-HEART-DISEASE, COHORT, cardiovascular diseases, Mendelian randomisation, EUROPEAN POPULATION, COMMON, Genetic Association Studies, Chromosomes, Human, Pair 15, MEN, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Atherosclerosis, INSULIN, Europe, Phenotype, 3121 General medicine, internal medicine and other clinical medicine, Asymptomatic Diseases, Linear Models, Female, hormones, hormone substitutes, and hormone antagonists, Proinsulin
Abstract: Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.
Published: 2017

22. Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Author: Song, C, Burgess, S, Eicher, JD, O'Donnell, CJ, Johnson, AD, Huang, J, Sabater-Lleal, M, Asselbergs, FW, Tregouet, D, Shin, SY, Ding, J, Baumert, J, Oudot-Mellakh, T, Folkersen, L, Smith, NL, Williams, SM, Ikram, MA, Kleber, ME, Becker, DM, Truong, V, Mychaleckyj, JC, Tang, W, Yang, Q, Sennblad, B, Moore, JH, Williams, FMK, Dehghan, A, Silbernagel, G, Schrijvers, EMC, Smith, S, Karakas, M, Tofler, GH, Silveira, A, Navis, GJ, Lohman, K, Chen, MH, Peters, A, Goel, A, Hopewell, JC, Chambers, JC, Saleheen, D, Lundmark, P, Psaty, BM, Strawbridge, RJ, Boehm, BO, Carter, AM, Meisinger, C, Peden, JF, Bis, JC, McKnight, B, Öhrvik, J, Taylor, K, Franzosi, MG, Seedorf, U, Collins, R, Franco-Cereceda, A, Syvänen, AC, Goodall, AH, Yanek, LR, Cushman, M, Müller-Nurasyid, M, Folsom, AR, Basu, S, Matijevic, N, Van Gilst, WH, Kooner, JS, Danesh, J, Clarke, R, Meigs, JB, Kathiresan, S, Reilly, MP, Klopp, N, Harris, TB, Winkelmann, BR, Grant, PJ, Hillege, HL, Watkins, H, Spector, TD, Becker, LC, Tracy, RP, März, W, Uitterlinden, AG, Eriksson, P, Cambien, F, Morange, PE, Koenig, W, Soranzo, N, Van der Harst, P, Liu, Y, Hamsten, A, Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Chasman, DI, Smith, AV, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Virology, Clinical Genetics, Obstetrics & Gynecology, and Gastroenterology & Hepatology
Subjects: 0301 basic medicine, Blood Glucose, Aging, Cardiac & Cardiovascular Systems, Epidemiology, medicine.medical_treatment, Genome-wide association study, Coronary Disease, Review, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, single nucleotide polymorphism, GENETIC-VARIANTS, Odds Ratio, ARTERY-DISEASE, METABOLIC SYNDROME, genome‐wide association study, INSULIN-RESISTANCE, education.field_of_study, Systematic Review and Meta‐Analysis, Fibrinolysis, Incidence, Mendelian Randomization Analysis, Single Nucleotide, C-REACTIVE PROTEIN, 3. Good health, Observational Studies as Topic, plasminogen activator inhibitor type 1, Heart Disease, CARDIOVASCULAR-DISEASE, Plasminogen activator inhibitor-1, Cardiology, Cardiology and Cardiovascular Medicine, Risk assessment, Lipoproteins, HDL, Life Sciences & Biomedicine, medicine.medical_specialty, HDL, Lipoproteins, Population, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, Genetic, Association Studies, Clinical Research, Internal medicine, Mendelian randomization, Plasminogen Activator Inhibitor 1, Journal Article, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Polymorphism, coronary heart disease, education, Heart Disease - Coronary Heart Disease, Science & Technology, genome-wide association study, business.industry, coronary heart disease ■ genome‐wide association study ■ Mendelian randomization ■ plasminogen activator inhibitor type 1 ■ single nucleotide polymorphism, Odds ratio, SUMMARIZED DATA, 030104 developmental biology, Endocrinology, MYOCARDIAL-INFARCTION, chemistry, Multivariate Analysis, Cardiovascular System & Cardiology, business, Biomarkers, Genome-Wide Association Study
Abstract: Background Plasminogen activator inhibitor type 1 ( PAI ‐1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI ‐1 levels are associated with increased risk of coronary heart disease ( CHD ). However, it is unclear whether the association reflects a causal influence of PAI ‐1 on CHD risk. Methods and Results To evaluate the association between PAI ‐1 and CHD , we applied a 3‐step strategy. First, we investigated the observational association between PAI ‐1 and CHD incidence using a systematic review based on a literature search for PAI ‐1 and CHD studies. Second, we explored the causal association between PAI ‐1 and CHD using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of PAI ‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood PAI ‐1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age‐ and sex‐adjusted model. The effect size was reduced in studies using a multivariable‐adjusted model (odds ratio=1.46; 95% CI : 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI ‐1 level on CHD risk (odds ratio=1.22 per unit increase of log‐transformed PAI ‐1; 95% CI : 1.01, 1.47). In addition, we also detected a causal effect of PAI ‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. Conclusions Our study indicates a causal effect of elevated PAI ‐1 level on CHD risk, which may be mediated by glucose dysfunction.
Published: 2017

23. Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease

Author: Folkersen, L, Fauman, E, Sabater-Lleal, M, Strawbridge, R, Frånberg, M, Sennblad, B, Baldassarre, D, Veglia, F, Humphries, S, Rauramaa, R, de Faire, U, Smit, A, Giral, P, Kurl, S, Mannarino, E, Enroth, S, Johansson, Å, Gustafsson, S, Lind, L, Lindgren, C, Morris, A, Giedraitis, V, Silveira, A, Franco-Cereceda, A, Tremoli, E, group, IMPROVE study, Gyllensten, U, Ingelsson, E, Brunak, S, Eriksson, P, Ziemek, D, Hamsten, A, Mälarstig, A, School of Medicine / Biomedicine, Groningen Kidney Center (GKC), and Vascular Ageing Programme (VAP)
Subjects: Male, 0301 basic medicine, Medicin och hälsovetenskap, Cancer Research, GENOME-WIDE ASSOCIATION, INTIMA-MEDIA THICKNESS, GENETIC-VARIANTS, MENDELIAN RANDOMIZATION, EXPRESSION, RISK, POPULATION, CELLS, GWAS, LIFE, Gene Expression, Genome-wide association study, Coronary Artery Disease, Disease, Cardiovascular Medicine, Biochemistry, Vascular Medicine, Medical and Health Sciences, 0302 clinical medicine, Medicine and Health Sciences, Coronary Heart Disease, Genetics (clinical), Regulation of gene expression, Genetics, education.field_of_study, Blood Proteins, Genomics, Cardiovascular Diseases, Female, Research Article, lcsh:QH426-470, Quantitative Trait Loci, Population, Cardiology, Quantitative trait locus, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Mendelian randomization, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Gene Regulation, education, Molecular Biology, Genotyping, Ecology, Evolution, Behavior and Systematics, Plasma Proteins, Biology and Life Sciences, Proteins, Computational Biology, Human Genetics, Genome Analysis, lcsh:Genetics, 030104 developmental biology, Genetic Loci, Expression quantitative trait loci, Biomarkers, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p, published version, peerReviewed
Published: 2017
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24. H19 Induces AAA Development and Progression

Author: Li, D.Y., primary, Jin, H., additional, Chernogubova, E., additional, Pelisek, J., additional, Karlsson, J., additional, Sennblad, B., additional, and Liu, S., additional
Published: 2018
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25. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), Cupples, L.A. (Adrienne), Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), and Cupples, L.A. (Adrienne)
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting
Published: 2017
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26. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), Cupples, L. A. (L. Adrienne), Justice, A. E. (Anne E.), Winkler, T. W. (Thomas W.), Feitosa, M. F. (Mary F.), Graff, M. (Misa), Fisher, V. A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J. S. (Julius S.), Ahluwalia, T. S. (Tarunveer S.), Chu, A. Y. (Audrey Y.), Heard-Costa, N. L. (Nancy L.), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J. D. (John D.), Kutalik, Z. (Zoltan), Xue, L. (Luting), Mahajan, A. (Anubha), Renstrom, F. (Frida), Wu, J. (Joseph), Qi, Q. (Qibin), Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L. F. (Lawrence F.), Bonnefond, A. (Amelie), Bragg, J. (Jennifer), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M. N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J. E. (Jennifer E.), Jackson, A. U. (Anne U.), Justesen, J. M. (Johanne Marie), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M. E. (Marcus E.), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R. P. (Rita P. S.), Mueller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A. V. (Albert Vernon), Smith, J. A. (Jennifer A.), Stancakova, A. (Alena), Strawbridge, R. J. (Rona J.), Stringham, H. M. (Heather M.), Sung, Y. J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), van der Laan, S. W. (Sander W.), van der Most, P. J. (Peter J.), Van Vliet-Ostaptchouk, J. V. (Jana V.), Vedantam, S. L. (Sailaja L.), Verweij, N. (Niek), Vink, J. M. (Jacqueline M.), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J. H. (Jing Hua), Zimmermann, M. E. (Martina E.), Zubair, N. (Niha), Abecasis, G. R. (Goncalo R.), Adair, L. S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S. J. (Stephan J. L.), Bartz, T. M. (Traci M.), Beilby, J. (John), Bergman, R. N. (Richard N.), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E. (Eric), Bonnycastle, L. L. (Lori L.), Bottinger, E. (Erwin), Braga, D. (Daniele), Buckley, B. M. (Brendan M.), Buyske, S. (Steve), Campbell, H. (Harry), Chambers, J. C. (John C.), Collins, F. S. (Francis S.), Curran, J. E. (Joanne E.), de Borst, G. J. (Gert J.), de Craen, A. J. (Anton J. M.), de Geus, E. J. (Eco J. C.), Dedoussis, G. (George), Delgado, G. E. (Graciela E.), den Ruijter, H. M. (Hester M.), Eiriksdottir, G. (Gudny), Eriksson, A. L. (Anna L.), Esko, T. (Tonu), Faul, J. D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T. B. (Tanja B.), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Goran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T. B. (Tamara B.), Hartman, C. A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. D. (Nicholas D.), Heath, A. C. (Andrew C.), Hernandez, D. (Dena), Hindorff, L. (Lucia), Hocking, L. J. (Lynne J.), Hollensted, M. (Mette), Holmen, O. L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J. J. (Jouke Jan), Huang, J. (Jie), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. L. (Alan L.), Jansson, J.-O. (John-Olov), Järvelin, M.-R. (Marjo-Riitta), Jhun, M. A. (Min A.), Jorgensen, M. E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H. A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Kramer, B. K. (Bernhard K.), Kuusisto, J. (Johanna), Kvaloy, K. (Kirsti), Lakka, T. A. (Timo A.), Langenberg, C. (Claudia), Launer, L. J. (Lenore J.), Leander, K. (Karin), Lee, N. R. (Nanette R.), Lind, L. (Lars), Lindgren, C. M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stephane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P. A. (Pamela A. F.), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N. G. (Nicholas G.), McKenzie, C. A. (Colin A.), McKnight, B. (Barbara), Mellstrom, D. (Dan), Menni, C. (Cristina), Montgomery, G. W. (Grant W.), Musk, A. W. (A. W. (Bill)), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I. M. (Ilja M.), Oldehinkel, A. J. (Albertine J.), Olden, M. (Matthias), Ong, K. K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P. A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D. J. (David J.), Raitakari, O. T. (Olli T.), Rankinen, T. (Tuomo), Rao, D. C. (D. C.), Rasmussen-Torvik, L. J. (Laura J.), Rawal, R. (Rajesh), Rice, T. (Treva), Ridker, P. M. (Paul M.), Rose, L. M. (Lynda M.), Bien, S. A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M. A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R. A. (Robert A.), Sennblad, B. (Bengt), Siemelink, M. A. (Marten A.), Silbernagel, G. (Gunther), Slagboom, P. E. (P. Eline), Snieder, H. (Harold), Staessen, J. A. (Jan A.), Stott, D. J. (David J.), Swertz, M. A. (Morris A.), Swift, A. J. (Amy J.), Taylor, K. D. (Kent D.), Tayo, B. O. (Bamidele O.), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A. G. (Andre G.), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Volzke, H. (Henry), Vonk, J. M. (Judith M.), Waeber, G. (Gerard), Waldenberger, M. (Melanie), Westendorp, R. G. (R. G. J.), Wild, S. (Sarah), Willemsen, G. (Gonneke), Wolffenbuttel, B. H. (Bruce H. R.), Wong, A. (Andrew), Wright, A. F. (Alan F.), Zhao, W. (Wei), Zillikens, M. C. (M. Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Boger, C. A. (Carsten A.), Boomsma, D. I. (Dorret I.), Bouchard, C. (Claude), Bruinenberg, M. (Marcel), Chasman, D. I. (Daniel I.), Chen, Y. I. (Yii-Der Ida), Chines, P. S. (Peter S.), Cooper, R. S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), de Faire, U. (Ulf), Ferrucci, L. (Luigi), Franks, P. W. (Paul W.), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.-J. (Hans-Jorgen), Gudnason, V. (Vilmundur), Haiman, C. A. (Christopher A.), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A. D. (Andrew D.), Jukema, W. (Wouter), Kardia, S. L. (Sharon L. R.), Kivimäki, M. (Mika), Kooner, J. S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), Marz, W. (Winfried), McCarthy, M. I. (Mark I.), Metspalu, A. (Andres), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Palmer, L. J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B. M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B. H. (Blair H.), Sorensen, T. I. (Thorkild I. A.), Strauch, K. (Konstantin), Tiemeier, H. (Henning), Tremoli, E. (Elena), Van der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N. J. (Nicholas J.), Weir, D. R. (David R.), Whitfield, J. B. (John B.), Wilson, J. F. (James F.), Tyrrell, J. (Jessica), Frayling, T. M. (Timothy M.), Barroso, I. (Ines), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C. S. (Caroline S.), Hirschhorn, J. N. (Joel N.), Hunter, D. J. (David J.), Spector, T. D. (Tim D.), Strachan, D. P. (David P.), van Duijn, C. M. (Cornelia M.), Heid, I. M. (Iris M.), Mohlke, K. L. (Karen L.), Marchini, J. (Jonathan), Loos, R. J. (Ruth J. F.), Kilpeläinen, T. O. (Tuomas O.), Liu, C.-T. (Ching-Ti), Borecki, I. B. (Ingrid B.), North, K. E. (Kari E.), and Cupples, L. A. (L. Adrienne)
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Published: 2017

27. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author: Strawbridge, RJ, Silveira, A, den Hoed, M, Gustafsson, S, Luan, JA, Rybin, D, Dupuis, J, Li-Gao, RF, Kavousi, Maryam, Dehghan, A, Haljas, K, Lahti, J, Gadin, JR, Backlund, A, de Faire, U, Gertow, K, Giral, P, Goel, A, Humphries, SE, Kurl, S, Langenberg, C, Lannfelt, LL, Lind, L, Lindgren, CCM, Mannarino, E, Mook, Dennis, Morris, AP, de Mutsert, R, Rauramaa, R, Saliba-Gustafsson, P, Sennblad, B, Smit, AJ, Syvanen, AC, Tremoli, E, Veglia, F, Zethelius, B, Bjorck, HM, Eriksson, JG, Hofman, Bert, Franco Duran, OH, Watkins, H, Jukema, JW, Florez, JC, Wareham, NJ, Meigs, JB, Ingelsson, E, Baldassarre, D, Hamsten, A, Strawbridge, RJ, Silveira, A, den Hoed, M, Gustafsson, S, Luan, JA, Rybin, D, Dupuis, J, Li-Gao, RF, Kavousi, Maryam, Dehghan, A, Haljas, K, Lahti, J, Gadin, JR, Backlund, A, de Faire, U, Gertow, K, Giral, P, Goel, A, Humphries, SE, Kurl, S, Langenberg, C, Lannfelt, LL, Lind, L, Lindgren, CCM, Mannarino, E, Mook, Dennis, Morris, AP, de Mutsert, R, Rauramaa, R, Saliba-Gustafsson, P, Sennblad, B, Smit, AJ, Syvanen, AC, Tremoli, E, Veglia, F, Zethelius, B, Bjorck, HM, Eriksson, JG, Hofman, Bert, Franco Duran, OH, Watkins, H, Jukema, JW, Florez, JC, Wareham, NJ, Meigs, JB, Ingelsson, E, Baldassarre, D, and Hamsten, A
Published: 2017

28. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, Cupples, LA, Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, and Cupples, LA
Published: 2017

29. Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Author: Butterworth, As, Braund, Ps, Farrall, M, Hardwick, Rj, Saleheen, D, Peden, Jf, Soranzo, N, Chambers, Jc, Sivapalaratnam, S, Kleber, Me, Keating, B, Qasim, A, Klopp, N, Erdmann, J, Assimes, Tl, Ball, Sg, Balmforth, Aj, Barnes, Ta, Basart, H, Baumert, J, Bezzina, Cr, Boerwinkle, E, Boehm, Bo, Brocheton, J, Bugert, P, Cambien, F, Clarke, R, Codd, V, Collins, R, Couper, D, Cupples, La, de Jong JS, Diemert, P, Ejebe, K, Elbers, Cc, Elliott, P, Fornage, M, Franzosi, Mg, Frossard, P, Garner, S, Goel, A, Goodall, Ah, Hengstenberg, C, Hunt, Se, Kastelein, Jj, Klungel, Oh, Klüter, H, Koch, K, König, Ir, Kooner, As, Laaksonen, R, Lathrop, M, Li, M, Liu, K, Mcpherson, R, Musameh, Md, Musani, S, Nelson, Cp, O'Donnell, Cj, Ongen, H, Papanicolaou, G, Peters, A, Peters, Bj, Potter, S, Psaty, Bm, Qu, L, Rader, Dj, Rasheed, A, Rice, C, Scott, J, Seedorf, U, Sehmi, Js, Sotoodehnia, N, Stark, K, Stephens, J, van der Schoot CE, van der Schouw YT, Thorsteinsdottir, U, Tomaszewski, M, van der Harst, P, Vasan, Rs, Wilde, Aa, Willenborg, C, Winkelmann, Br, Zaidi, M, Zhang, W, Ziegler, A, de Bakker PI, Koenig, W, Mätz, W, Trip, Md, Reilly, Mp, Kathiresan, S, Schunkert, H, Hamsten, A, Hall, As, Kooner, Js, Thompson, Sg, Thompson, Jr, Deloukas, P, Ouwehand, Wh, Watkins, H, Danesh, J, Samani, Nj, Barnes, T, Rafelt, S, Bruinsma, N, Dekker, Lr, Henriques, Jp, Koch, Kt, de Winter RJ, Alings, M, Allaart, Cf, Gorgels, Ap, Verheugt, Fw, Mueller, M, Meisinger, C, Derohannessian, S, Mehta, Nn, Ferguson, J, Hakonarson, H, Matthai, W, Wilensky, R, Hopewell, Jc, Parish, S, Linksted, P, Notman, J, Gonzalez, H, Young, A, Ostley, T, Munday, A, Goodwin, N, Verdon, V, Shah, S, Cobb, L, Edwards, C, Mathews, C, Gunter, R, Benham, J, Davies, C, Cobb, M, Crowther, J, Richards, A, Silver, M, Tochlin, S, Mozley, S, Clark, S, Radley, M, Kourellias, K, Silveira, A, Söderholm, B, Olsson, P, Barlera, S, Tognoni, G, Rust, S, Assmann, G, Heath, S, Zelenika, D, Gut, I, Green, F, Peden, J, Aly, A, Anner, K, Björklund, K, Blomgren, G, Cederschiöld, B, Danell Toverud, K, Eriksson, P, Grundstedt, U, Heinonen, M, Hellénius, Ml, van't Hooft, F, Husman, K, Lagercrantz, J, Larsson, A, Larsson, M, Mossfeldt, M, Mälarstig, A, Olsson, G, Sabater Lleal, M, Sennblad, B, Strawbridge, R, Öhrvik, J, Zaman, Ks, Mallick, Nh, Azhar, M, Samad, A, Ishaq, M, Shah, N, Samuel, M, Reilly, M, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, S, Andersen, K, Anderson, Jl, Ardissino, D, Becker, Lc, Becker, Dm, Berger, K, Bis, Jc, Boekholdt, Sm, Brown, Mj, Burnett, Ms, Buysschaert, I, Carlquist, Jf, Chen, L, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, J, Do, R, Doering, A, El Mokhtari NE, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, S, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Tennstedt, S, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Lambrechts, D, Leander, K, Lieb, W, Lettre, G, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Musunuru, K, Nahrstaedt, J, Nöthen, Mm, Olivieri, Oliviero, Peyvandi, F, Patel, Rs, Patterson, Cc, Quyyumi, Aa, Rallidis, Ls, Roosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Smith, Av, Smith, Tb, Snoep, Jd, Spertus, Ja, Stefansson, K, Stirrups, K, Stoll, M, Tang, Wh, Thorgeirsson, G, Thorleifsson, G, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Awells, G, Wichmann, He, Witteman, Jc, Wright, Bj, Ye, S, Quertermous, T, März, W, Blankenberg, S, Roberts, R, Onland Moret NC, van Setten, J, Verschuren, Wm, Boer, Jm, Wijmenga, C, Hofker, Mh, Maitland van der Zee AH, de Boer, A, Grobbee, De, Attwood, T, Belz, S, Braund, P, Cooper, J, Crisp Hihn, A, Foad, N, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd Jones, H, Lugauer, I, Lundmark, P, Moore, Js, Muir, D, Murray, E, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Syvannen, Ac, Wallace, C., Cardiologie, RS: CAPHRI School for Public Health and Primary Care, Vascular Medicine, Other departments, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Landsteiner Laboratory, Clinical Haematology, Pulmonology, and Medical Research Council (MRC)
Subjects: Male, Cancer Research, Candidate gene, Epidemiology, Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cardiovascular, 0302 clinical medicine, GENETICS & HEREDITY, Genetics (clinical), Genetics, 0303 health sciences, Cardiovascular diseases [NCEBP 14], Middle Aged, 3. Good health, CYP17A1, Genetic Epidemiology, Genome-wide association, Myocardial-infarction, Susceptibility loci, Risk, Atherosclerosis, Metanalysis, Lipoprotein, Medicine, Female, Life Sciences & Biomedicine, Research Article, Asian Continental Ancestry Group, Adult, SUSCEPTIBILITY LOCI, lcsh:QH426-470, European Continental Ancestry Group, Biology, Polymorphism, Single Nucleotide, coronary artery disease, genetics, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Asian People, Genetic variation, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Allele, Molecular Biology, Gene, METAANALYSIS, Ecology, Evolution, Behavior and Systematics, Genetic Association Studies, Cardiovascular Disease Epidemiology, Alleles, 030304 developmental biology, Aged, 0604 Genetics, Science & Technology, Case-control study, Genetic Variation, Human Genetics, Odds ratio, large-scale gene analysis, lcsh:Genetics, LIPOPROTEIN, MYOCARDIAL-INFARCTION, ATHEROSCLEROSIS, Case-Control Studies, Genetics of Disease, IBC 50K CAD Consortium, Developmental Biology, Genome-Wide Association Study
Abstract: Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p, Author Summary Coronary artery disease (CAD) has a strong genetic basis that remains poorly characterised. Using a custom-designed array, we tested the association with CAD of almost 50,000 common and low frequency variants in ∼2,000 genes of known or suspected cardiovascular relevance. We genotyped the array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin) and attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. We report the novel association of variants in or near four genes with CAD and in additional studies identify potential mechanisms by which some of these novel variants affect CAD risk. Interestingly, we found that these variants, as well as the majority of previously reported CAD variants, have similar associations in Europeans and South Asians. Contrary to prior expectations, many previously suggested candidate genes did not show evidence of any effect on CAD risk, and neither did we identify any novel low frequency alleles with strong effects amongst the genes tested. Discovery of novel genes associated with heart disease may help to further understand the aetiology of cardiovascular disease and identify new targets for therapeutic interventions.
Published: 2016

30. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

Author: Huffman, JE, De Vries, PS, Morrison, AC, Sabater-Lleal, M, Kacprowski, T, Auer, PL, Brody, JA, Chasman, DI, Chen, MH, Guo, X, Lin, LA, Marioni, RE, Müller-Nurasyid, M, Yanek, LR, Pankratz, N, Grove, ML, De Maat, MPM, Cushman, M, Wiggins, KL, Qi, L, Sennblad, B, Harris, SE, Polasek, O, Riess, H, Rivadeneira, F, Rose, LM, Goel, A, Taylor, KD, Teumer, A, Uitterlinden, AG, Vaidya, D, Yao, J, Tang, W, Levy, D, Waldenberger, M, Becker, DM, Folsom, AR, Giulianini, F, Greinacher, A, Hofman, A, Huang, CC, Kooperberg, C, Silveira, A, Starr, JM, Strauch, K, Strawbridge, RJ, Wright, AF, McKnight, B, Franco, OH, Zakai, N, Mathias, RA, Psaty, BM, Ridker, PM, Tofler, GH, Völker, U, Watkins, H, Fornage, M, Hamsten, A, Deary, IJ, Boerwinkle, E, Koenig, W, Rotter, JI, Hayward, C, Dehghan, A, Reiner, AP, and O'Donnell, CJ
Abstract: © 2015, American Society of Hematology. All rights reserved. Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and
Published: 2015
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31. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author: Wessel, J. Chu, A.Y. Willems, S.M. Wang, S. Yaghootkar, H. Brody, J.A. Dauriz, M. Hivert, M.-F. Raghavan, S. Lipovich, L. Hidalgo, B. Fox, K. Huffman, J.E. An, P. Lu, Y. Rasmussen-Torvik, L.J. Grarup, N. Ehm, M.G. Li, L. Baldridge, A.S. Stančáková, A. Abrol, R. Besse, C. Boland, A. Bork-Jensen, J. Fornage, M. Freitag, D.F. Garcia, M.E. Guo, X. Hara, K. Isaacs, A. Jakobsdottir, J. Lange, L.A. Layton, J.C. Li, M. Hua Zhao, J. Meidtner, K. Morrison, A.C. Nalls, M.A. Peters, M.J. Sabater-Lleal, M. Schurmann, C. Silveira, A. Smith, A.V. Southam, L. Stoiber, M.H. Strawbridge, R.J. Taylor, K.D. Varga, T.V. Allin, K.H. Amin, N. Aponte, J.L. Aung, T. Barbieri, C. Bihlmeyer, N.A. Boehnke, M. Bombieri, C. Bowden, D.W. Burns, S.M. Chen, Y. Chen, Y.-D. Cheng, C.-Y. Correa, A. Czajkowski, J. Dehghan, A. Ehret, G.B. Eiriksdottir, G. Escher, S.A. Farmaki, A.-E. Frånberg, M. Gambaro, G. Giulianini, F. Goddard, W.A. Goel, A. Gottesman, O. Grove, M.L. Gustafsson, S. Hai, Y. Hallmans, G. Heo, J. Hoffmann, P. Ikram, M.K. Jensen, R.A. Jørgensen, M.E. Jørgensen, T. Karaleftheri, M. Khor, C.C. Kirkpatrick, A. Kraja, A.T. Kuusisto, J. Lange, E.M. Lee, I.T. Lee, W.-J. Leong, A. Liao, J. Liu, C. Liu, Y. Lindgren, C.M. Linneberg, A. Malerba, G. Mamakou, V. Marouli, E. Maruthur, N.M. Matchan, A. McKean-Cowdin, R. McLeod, O. Metcalf, G.A. Mohlke, K.L. Muzny, D.M. Ntalla, I. Palmer, N.D. Pasko, D. Peter, A. Rayner, N.W. Renström, F. Rice, K. Sala, C.F. Sennblad, B. Serafetinidis, I. Smith, J.A. Soranzo, N. Speliotes, E.K. Stahl, E.A. Stirrups, K. Tentolouris, N. Thanopoulou, A. Torres, M. Traglia, M. Tsafantakis, E. Javad, S. Yanek, L.R. Zengini, E. Becker, D.M. Bis, J.C. Brown, J.B. Adrienne Cupples, L. Hansen, T. Ingelsson, E. Karter, A.J. Lorenzo, C. Mathias, R.A. Norris, J.M. Peloso, G.M. Sheu, W.H.-H. Toniolo, D. Vaidya, D. Varma, R. Wagenknecht, L.E. Boeing, H. Bottinger, E.P. Dedoussis, G. Deloukas, P. Ferrannini, E. Franco, O.H. Franks, P.W. Gibbs, R.A. Gudnason, V. Hamsten, A. Harris, T.B. Hattersley, A.T. Hayward, C. Hofman, A. Jansson, J.-H. Langenberg, C. Launer, L.J. Levy, D. Oostra, B.A. O'Donnell, C.J. O'Rahilly, S. Padmanabhan, S. Pankow, J.S. Polasek, O. Province, M.A. Rich, S.S. Ridker, P.M. Rudan, I. Schulze, M.B. Smith, B.H. Uitterlinden, A.G. Walker, M. Watkins, H. Wong, T.Y. Zeggini, E. Laakso, M. Borecki, I.B. Chasman, D.I. Pedersen, O. Psaty, B.M. Shyong Tai, E. Van Duijn, C.M. Wareham, N.J. Waterworth, D.M. Boerwinkle, E. Linda Kao, W.H. Florez, J.C. Loos, R.J.F. Wilson, J.G. Frayling, T.M. Siscovick, D.S. Dupuis, J. Rotter, J.I. Meigs, J.B. Scott, R.A. Goodarzi, M.O.
Abstract: Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01mmoll-1, P=3.4 × 10-12), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035pmolinsulin mmolglucose-1, P=0.048), but higher 2-h glucose (β=0.16±0.05mmoll-1, P=4.3 × 10-4). We identify a gene-based association with FG at G6PC2 (p SKAT =6.8 × 10-6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004mmoll-1, P=1.3 × 10-8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility. © 2015 Macmillan Publishers Limited. All rights reserved.
Published: 2015

32. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: Evidence from genetic analysis and randomised trials

Author: Swerdlow, DI, Preiss, D, Kuchenbaecker, KB, Holmes, MV, Engmann, JEL, Shah, T, Sofat, R, Stender, S, Johnson, PCD, Scott, RA, Leusink, M, Verweij, N, Sharp, SJ, Guo, Y, Giambartolomei, C, Chung, C, Peasey, A, Amuzu, A, Li, K, Palmen, J, Howard, P, Cooper, JA, Drenos, F, Li, YR, Lowe, G, Gallacher, J, Stewart, MCW, Tzoulaki, I, Buxbaum, SG, Van Der A, DL, Forouhi, NG, Onland-Moret, NC, Van Der Schouw, YT, Schnabel, RB, Hubacek, JA, Kubinova, R, Baceviciene, M, Tamosiunas, A, Pajak, A, Topor-Madry, R, Stepaniak, U, Malyutina, S, Baldassarre, D, Sennblad, B, Tremoli, E, De Faire, U, Veglia, F, Ford, I, Jukema, JW, Westendorp, RGJ, De Borst, GJ, De Jong, PA, Algra, A, Spiering, W, Der Zee, AHMV, Klungel, OH, De Boer, A, Doevendans, PA, Eaton, CB, Robinson, JG, Duggan, D, Kjekshus, J, Downs, JR, Gotto, AM, Keech, AC, Marchioli, R, Tognoni, G, Sever, PS, Poulter, NR, Waters, DD, Pedersen, TR, Amarenco, P, Nakamura, H, McMurray, JJV, Lewsey, JD, Chasman, DI, Ridker, PM, Maggioni, AP, Tavazzi, L, Ray, KK, Seshasai, SRK, Manson, JE, Price, JF, Whincup, PH, Morris, RW, and Lawlor, DA
Abstract: © 2015 Swerdlow et al. Open Access article distributed under the terms of CC BY. Background Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. Methods We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. Findings Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). Interpretation The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. Funding The funding sources are cited at the end of the paper.
Published: 2015
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33. Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps

Author: Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), Soranzo, N. (Nicole), Iotchkova, V. (Valentina), Huang, J. (Jian), Morris, J.A. (John A), Jain, D. (Deepti), Barbieri, C. (Caterina), Walter, K. (Klaudia), Min, J. (Josine), Chen, L. (Lu), Astle, W. (William), Cocca, M. (Massimiliano), Deelen, P. (Patrick), Elding, H. (Heather), Farmaki, A.-E. (Aliki-Eleni), Franklin, C.S. (Christopher), Frånberg, M. (Mattias), Gaunt, T.R. (Tom), Hofman, A. (Albert), Jiang, T. (Tao), Kleber, M.E. (Marcus), Lachance, G. (Genevieve), Luan, J. (Jian'An), Malerba, G. (Giovanni), Matchan, A. (Angela), Mead, D. (Daniel), Memari, Y. (Yasin), Ntalla, I. (Ioanna), Panoutsopoulou, K. (Kalliope), Pazoki, R. (Raha), Perry, J.R.B. (John), Rivadeneira Ramirez, F. (Fernando), Sabater-Lleal, M. (Maria), Sennblad, B. (Bengt), Shin, S.-Y., Southam, L. (Lorraine), Traglia, M. (Michela), Dijk, F. (Freerk) van, Leeuwen, E.M. (Elisa) van, Zaza, G. (Gianluigi), Zhang, W. (Weihua), Amin, N. (Najaf), Butterworth, A.S. (Adam), Chambers, J.C. (John), Dedoussis, G.V. (George), Dehghan, A. (Abbas), Franco, O.H. (Oscar), Franke, L. (Lude), Frontini, M. (Mattia), Gambaro, G. (Giovanni), Gasparini, P. (Paolo), Hamsten, A. (Anders), Issacs, A. (Aaron), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Langenberg, C. (Claudia), März, W. (Winfried), Scott, R.A. (Robert), Swertz, M.A. (Morris A), Toniolo, D. (Daniela), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Maurano, M.T. (Matthew T.), Timpson, N.J. (Nicholas), Reiner, A. (Alexander), Auer, P. (Paul), and Soranzo, N. (Nicole)
Abstract: Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) < 1%) or low-frequency (1% < MAF < 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.
Published: 2016
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34. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Author: Vries, P.S. (Paul) de, Chasman, D.I. (Daniel), Sabater-Lleal, M. (Maria), Chen, M.-H. (Ming-Huei), Huffman, J.E. (Jennifer E.), Steri, M. (Maristella), Tang, W. (Weihong), Teumer, A. (Alexander), Marioni, R.E. (Riccardo), Grossmann, V. (Vera), Hottenga, J.J. (Jouke Jan), Trompet, S. (Stella), Müller-Nurasyid, M. (Martina), Zhao, J.H. (Jing Hua), Brody, J.A. (Jennifer A.), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Wang, J.J. (Jie Jin), Auer, P. (Paul), Attia, J. (John), Yanek, L.R. (Lisa), Ahluwalia, T.S. (Tarunveer Singh), Lahti, J. (Jari), Venturini, C. (Cristina), Tanaka, T. (Toshiko), Bielak, L.F. (Lawrence F.), Joshi, P.K. (Peter), Rocanin-Arjo, A. (Ares), Kolcic, I. (Ivana), Navarro, P. (Pau), Rose, L.M. (Lynda), Oldmeadow, C. (Christopher), Riess, H. (Helene), Mazur, J. (Johanna), Basu, S. (Saonli), Goel, A. (Anuj), Yang, Q. (Qiong), Ghanbari, M. (Mohsen), Willemsen, G. (Gonneke), Rumley, A. (Ann), Fiorillo, E. (Edoardo), Craen, A.J. (Anton) de, Grotevendt, A. (Anne), Scott, R.A. (Robert), Taylor, K.D. (Kent D.), Delgado, G.E. (Graciela E.), Yao, J. (Jie), Kifley, A. (Annette), Kooperberg, C. (Charles), Qayyum, Q. (Rehan), Lopez, L. (Lornam), Berentzen, T.L. (Tina L.), Räikkönen, K. (Katri), Mangino, M. (Massimo), Bandinelli, S. (Stefania), Peyser, P.A. (Patricia A.), Wild, S. (Sarah), Tregouet, D.-A. (David-Alexandre), Wright, A.F. (Alan), Marten, J. (Jonathan), Zemunik, T. (Tatijana), Morrison, A.C. (Alanna), Sennblad, B. (Bengt), Tofler, G.H. (Geoffrey), Maat, M.P.M. (Moniek) de, Geus, E.J.C. (Eco) de, Lowe, G.D. (Gordon D.), Zoledziewska, M. (Magdalena), Sattar, N. (Naveed), Binder, H. (Harald), Völker, U. (Uwe), Waldenberger, M. (Melanie), Khaw, K.-T. (Kay-Tee), McKnight, B. (Barbara), Huang, J. (Jian), Jenny, N.S. (Nancy), Holliday, E.G. (Elizabeth), Qi, L. (Lihong), Mcevoy, M.G. (Mark G.), Becker, D.M. (Diane), Starr, J.M. (John), Sarin, A.-P., Hysi, P.G. (Pirro), Hernandez, D.G. (Dena), Jhun, M.A. (Min A.), Campbell, H. (Harry), Hamsten, A. (Anders), Sarin, F. (Fernando), McArdle, W.L. (Wendy), Slagboom, P.E. (Eline), Zeller, T. (Tanja), Koenig, W. (Wolfgang), Psaty, B. (Brucem), Haritunians, T. (Talin), Liu, J. (Jingmin), Palotie, A. (Aarno), Uitterlinden, A.G. (André), Stott, D.J. (David J.), Hofman, A. (Albert), Franco, O.H. (Oscar), Polasek, O. (Ozren), Rudan, I. (Igor), Morange, P.-E. (P.), Wilson, J.F. (James F.), Kardia, S.L. (Sharon L.r), Ferrucci, L. (Luigi), Spector, T.D. (Timothy), Eriksson, J.G. (Johan G.), Hansen, T. (Torben), Deary, I.J. (Ian), Becker, L.C. (Lewis), Scott, R.J. (Rodney), Mitchell, P. (Paul), März, W. (Winfried), Wareham, N.J. (Nick J.), Peters, A. (Annette), Greinacher, A. (Andreas), Wild, P.S. (Philipp S.), Jukema, J.W. (Jan Wouter), Boomsma, D.I. (Dorret), Hayward, C. (Caroline), Cucca, F. (Francesco), Tracy, R.P. (Russell), Watkins, H. (Hugh), Reiner, A.P. (Alex P.), Folsom, A.R. (Aaron), Ridker, P.M. (Paul), O'Donnell, C.J. (Christopher J.), Smith, N.L. (Nicholas L.), Strachan, D.P. (David P.), Dehghan, A. (Abbas), Vries, P.S. (Paul) de, Chasman, D.I. (Daniel), Sabater-Lleal, M. (Maria), Chen, M.-H. (Ming-Huei), Huffman, J.E. (Jennifer E.), Steri, M. (Maristella), Tang, W. (Weihong), Teumer, A. (Alexander), Marioni, R.E. (Riccardo), Grossmann, V. (Vera), Hottenga, J.J. (Jouke Jan), Trompet, S. (Stella), Müller-Nurasyid, M. (Martina), Zhao, J.H. (Jing Hua), Brody, J.A. (Jennifer A.), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Wang, J.J. (Jie Jin), Auer, P. (Paul), Attia, J. (John), Yanek, L.R. (Lisa), Ahluwalia, T.S. (Tarunveer Singh), Lahti, J. (Jari), Venturini, C. (Cristina), Tanaka, T. (Toshiko), Bielak, L.F. (Lawrence F.), Joshi, P.K. (Peter), Rocanin-Arjo, A. (Ares), Kolcic, I. (Ivana), Navarro, P. (Pau), Rose, L.M. (Lynda), Oldmeadow, C. (Christopher), Riess, H. (Helene), Mazur, J. (Johanna), Basu, S. (Saonli), Goel, A. (Anuj), Yang, Q. (Qiong), Ghanbari, M. (Mohsen), Willemsen, G. (Gonneke), Rumley, A. (Ann), Fiorillo, E. (Edoardo), Craen, A.J. (Anton) de, Grotevendt, A. (Anne), Scott, R.A. (Robert), Taylor, K.D. (Kent D.), Delgado, G.E. (Graciela E.), Yao, J. (Jie), Kifley, A. (Annette), Kooperberg, C. (Charles), Qayyum, Q. (Rehan), Lopez, L. (Lornam), Berentzen, T.L. (Tina L.), Räikkönen, K. (Katri), Mangino, M. (Massimo), Bandinelli, S. (Stefania), Peyser, P.A. (Patricia A.), Wild, S. (Sarah), Tregouet, D.-A. (David-Alexandre), Wright, A.F. (Alan), Marten, J. (Jonathan), Zemunik, T. (Tatijana), Morrison, A.C. (Alanna), Sennblad, B. (Bengt), Tofler, G.H. (Geoffrey), Maat, M.P.M. (Moniek) de, Geus, E.J.C. (Eco) de, Lowe, G.D. (Gordon D.), Zoledziewska, M. (Magdalena), Sattar, N. (Naveed), Binder, H. (Harald), Völker, U. (Uwe), Waldenberger, M. (Melanie), Khaw, K.-T. (Kay-Tee), McKnight, B. (Barbara), Huang, J. (Jian), Jenny, N.S. (Nancy), Holliday, E.G. (Elizabeth), Qi, L. (Lihong), Mcevoy, M.G. (Mark G.), Becker, D.M. (Diane), Starr, J.M. (John), Sarin, A.-P., Hysi, P.G. (Pirro), Hernandez, D.G. (Dena), Jhun, M.A. (Min A.), Campbell, H. (Harry), Hamsten, A. (Anders), Sarin, F. (Fernando), McArdle, W.L. (Wendy), Slagboom, P.E. (Eline), Zeller, T. (Tanja), Koenig, W. (Wolfgang), Psaty, B. (Brucem), Haritunians, T. (Talin), Liu, J. (Jingmin), Palotie, A. (Aarno), Uitterlinden, A.G. (André), Stott, D.J. (David J.), Hofman, A. (Albert), Franco, O.H. (Oscar), Polasek, O. (Ozren), Rudan, I. (Igor), Morange, P.-E. (P.), Wilson, J.F. (James F.), Kardia, S.L. (Sharon L.r), Ferrucci, L. (Luigi), Spector, T.D. (Timothy), Eriksson, J.G. (Johan G.), Hansen, T. (Torben), Deary, I.J. (Ian), Becker, L.C. (Lewis), Scott, R.J. (Rodney), Mitchell, P. (Paul), März, W. (Winfried), Wareham, N.J. (Nick J.), Peters, A. (Annette), Greinacher, A. (Andreas), Wild, P.S. (Philipp S.), Jukema, J.W. (Jan Wouter), Boomsma, D.I. (Dorret), Hayward, C. (Caroline), Cucca, F. (Francesco), Tracy, R.P. (Russell), Watkins, H. (Hugh), Reiner, A.P. (Alex P.), Folsom, A.R. (Aaron), Ridker, P.M. (Paul), O'Donnell, C.J. (Christopher J.), Smith, N.L. (Nicholas L.), Strachan, D.P. (David P.), and Dehghan, A. (Abbas)
Abstract: Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels.We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ~120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indelswere examined.We identified 41 genome-wide significant fibrinogen loci; of which, 18were newly identified. Therewere no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration.
Published: 2016
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35. Correction: The influence of age and sex on genetic associations with adult body size and shape : a large-scale genome-wide interaction study.

Author: Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., 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L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., Loos, R.J., Winkler, T.W., Justice, A.E., Graff, M., Barata, L., Feitosa, M.F., Chu, S., Czajkowski, J., Esko, T., Fall, T., Kilpeläinen, T.O., Lu, Y., Mägi, R., Mihailov, E., Pers, T.H., Rüeger, S., Teumer, A., Ehret, G.B., Ferreira, T., Heard-Costa, N.L., Karjalainen, J., Lagou, V., Mahajan, A., Neinast, M.D., Prokopenko, I., Simino, J., Teslovich, T.M., Jansen, R., Westra, H.J., White, C.C., Absher, D., Ahluwalia, T.S., Ahmad, S., Albrecht, E., Alves, A.C., Bragg-Gresham, J.L., de Craen, A.J., Bis, J.C., Bonnefond, A., Boucher, G., Cadby, G., Cheng, Y.C., Chiang, C.W., Delgado, G., Demirkan, A., Dueker, N., Eklund, N., Eiriksdottir, G., Eriksson, J., Feenstra, B., Fischer, K., Frau, F., Galesloot, T.E., Geller, F., Goel, A., Gorski, M., Grammer, T.B., Gustafsson, S., Haitjema, S., Hottenga, J.J., Huffman, J.E., Jackson, A.U., Jacobs, K.B., Johansson, Å., Kaakinen, M., Kleber, M.E., Lahti, J., Mateo Leach, I., Lehne, B., Liu, Y., Lo, K.S., Lorentzon, M., Luan, J., Madden, P.A., Mangino, M., McKnight, B., Medina-Gomez, C., Monda, K.L., Montasser, M.E., Müller, G., Müller-Nurasyid, M., Nolte, I.M., Panoutsopoulou, K., Pascoe, L., Paternoster, L., Rayner, N.W., Renström, F., Rizzi, F., Rose, L.M., Ryan, K.A., Salo, P., Sanna, S., Scharnagl, H., Shi, J., Smith, A.V., Southam, L., Stančáková, A., Steinthorsdottir, V., Strawbridge, R.J., Sung, Y.J., Tachmazidou, I., Tanaka, T., Thorleifsson, G., Trompet, S., Pervjakova, N., Tyrer, J.P., Vandenput, L., van der Laan, S.W., van der Velde, N., van Setten, J., van Vliet-Ostaptchouk, J.V., Verweij, N., Vlachopoulou, E., Waite, L.L., Wang, S.R., Wang, Z., Wild, S.H., Willenborg, C., Wilson, J.F., Wong, A., Yang, J., Yengo, L., Yerges-Armstrong, L.M., Yu, L., Zhang, W., Zhao, J.H., Andersson, E.A., Bakker, S.J., Baldassarre, D., Banasik, K., Barcella, M., Barlassina, C., Bellis, C., Benaglio, P., Blangero, J., Blüher, M., Bonnet, F., Bonnycastle, L.L., Boyd, H.A., Bruinenberg, M., Buchman, A.S., Campbell, H., Chen, Y.I., Chines, P.S., Claudi-Boehm, S., Cole, J., Collins, F.S., de Geus, E.J., de Groot, L.C., Dimitriou, M., Duan, J., Enroth, S., Eury, E., Farmaki, A.E., Forouhi, N.G., Friedrich, N., Gejman, P.V., Gigante, B., Glorioso, N., Go, A.S., Gottesman, O., Gräßler, J., Grallert, H., Grarup, N., Gu, Y.M., Broer, L., Ham, A.C., Hansen, T., Harris, T.B., Hartman, C.A., Hassinen, M., Hastie, N., Hattersley, A.T., Heath, A.C., Henders, A.K., Hernandez, D., Hillege, H., Holmen, O., Hovingh, K.G., Hui, J., Husemoen, L.L., Hutri-Kähönen, N., Hysi, P.G., Illig, T., De Jager, P.L., Jalilzadeh, S., Jørgensen, T., Jukema, J.W., Juonala, M., Kanoni, S., Karaleftheri, M., Khaw, K.T., Kinnunen, L., Kittner, S.J., Koenig, W., Kolcic, I., Kovacs, P., Krarup, N.T., Kratzer, W., Krüger, J., Kuh, D., Kumari, M., Kyriakou, T., Langenberg, C., Lannfelt, L., Lanzani, C., Lotay, V., Launer, L.J., Leander, K., Lindström, J., Linneberg, A., Liu, Y.P., Lobbens, S., Luben, R., Lyssenko, V., Männistö, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Montgomery, G.W., Morris, A.P., Narisu, N., Nelis, M., Ong, K.K., Palotie, A., Pérusse, L., Pichler, I., Pilia, M.G., Pouta, A., Rheinberger, M., Ribel-Madsen, R., Richards, M., Rice, K.M., Rice, T.K., Rivolta, C., Salomaa, V., Sanders, A.R., Sarzynski, M.A., Scholtens, S., Scott, R.A., Scott, W.R., Sebert, S., Sengupta, S., Sennblad, B., Seufferlein, T., Silveira, A., Slagboom, P.E., Smit, J.H., Sparsø, T.H., Stirrups, K., Stolk, R.P., Stringham, H.M., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tan, S.T., Thorand, B., Tönjes, A., Tremblay, A., Tsafantakis, E., van der Most, P.J., Völker, U., Vohl, M.C., Vonk, J.M., Waldenberger, M., Walker, R.W., Wennauer, R., Widén, E., Willemsen, G., Wilsgaard, T., Wright, A.F., Zillikens, M.C., van Dijk, S.C., van Schoor, N.M., Asselbergs, F.W., de Bakker, P.I., Beckmann, J.S., Beilby, J., Bennett, D.A., Bergman, R.N., Bergmann, S., Böger, C.A., Boehm, B.O., Boerwinkle, E., Boomsma, D.I., Bornstein, S.R., Bottinger, E.P., Bouchard, C., Chambers, J.C., Chanock, S.J., Chasman, D.I., Cucca, F., Cusi, D., Dedoussis, G., Erdmann, J., Eriksson, J.G., Evans, D.A., de Faire, U., Farrall, M., Ferrucci, L., Ford, I., Franke, L., Franks, P.W., Froguel, P., Gansevoort, R.T., Gieger, C., Grönberg, H., Gudnason, V., Gyllensten, U., Hall, P., Hamsten, A., van der Harst, P., Hayward, C., Heliövaara, M., Hengstenberg, C., Hicks, A.A., Hingorani, A., Hofman, A., Hu, F., Huikuri, H.V., Hveem, K., James, A.L., Jordan, J.M., Jula, A., Kähönen, M., Kajantie, E., Kathiresan, S., Kiemeney, L.A., Kivimaki, M., Knekt, P.B., Koistinen, H.A., Kooner, J.S., Koskinen, S., Kuusisto, J., Maerz, W., Martin, N.G., Laakso, M., Lakka, T.A., Lehtimäki, T., Lettre, G., Levinson, D.F., Lind, L., Lokki, M.L., Mäntyselkä, P., Melbye, M., Metspalu, A., Mitchell, B.D., Moll, F.L., Murray, J.C., Musk, A.W., Nieminen, M.S., Njølstad, I., Ohlsson, C., Oldehinkel, A.J., Oostra, B.A., Palmer, L.J., Pankow, J.S., Pasterkamp, G., Pedersen, N.L., Pedersen, O., Penninx, B.W., Perola, M., Peters, A., Polaek, O., Pramstaller, P.P., Psaty, B.M., Qi, L., Quertermous, T., Raitakari, O.T., Rankinen, T., Rauramaa, R., Ridker, P.M., Rioux, J.D., Rivadeneira, F., Rotter, J.I., Rudan, I., den Ruijter, H.M., Saltevo, J., Sattar, N., Schunkert, H., Schwarz, P.E., Shuldiner, A.R., Sinisalo, J., Snieder, H., Sørensen, T.I., Spector, T.D., Staessen, J.A., Stefania, B., Thorsteinsdottir, U., Stumvoll, M., Tardif, J.C., Tremoli, E., Tuomilehto, J., Uitterlinden, A.G., Uusitupa, M., Verbeek, A.L., Vermeulen, S.H., Viikari, J.S., Vitart, V., Völzke, H., Vollenweider, P., Waeber, G., Walker, M., Wallaschofski, H., Wareham, N.J., Watkins, H., Zeggini, E., arcOGEN, Consortium, CHARGE, Consortium, DIAGRAM, Consortium, GLGC, Consortium, Global-BPGen, Consortium, ICBP, Consortium, MAGIC, Consortium, Chakravarti, A., Clegg, D.J., Cupples, L.A., Gordon-Larsen, P., Jaquish, C.E., Rao, D.C., Abecasis, G.R., Assimes, T.L., Barroso, I., Berndt, S.I., Boehnke, M., Deloukas, P., Fox, C.S., Groop, L.C., Hunter, D.J., Ingelsson, E., Kaplan, R.C., McCarthy, M.I., Mohlke, K.L., O'Connell, J.R., Schlessinger, D., Strachan, D.P., Stefansson, K., van Duijn, C.M., Hirschhorn, J.N., Lindgren, C.M., Heid, I.M., North, K.E., Borecki, I.B., Kutalik, Z., and Loos, R.J.
Abstract: This corrects the article DOI: 10.1371/journal.pgen.1005378.
Published: 2016

36. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author: STRAWBRIDGE RJ, DUPUIS J, PROKOPENKO I, BARKER A, AHLQVIST E, RYBIN D, PETRIE JR, TRAVERS ME, BOUATIA-NAJI N, DIMAS AS, NICA A, WHEELER E, CHEN H, VOIGHT BF, TANEERA J, KANONI S, PEDEN JF, TURRINI F, GUSTAFSSON S, ZABENA C, ALMGREN P, BARKER DJ, BARNES D, DENNISON EM, ERIKSSON JG, ERIKSSON P, EURY E, FOLKERSEN L, FOX CS, FRAYLING TM, GOEL A, GU HF, HORIKOSHI M, ISOMAA B, JACKSON AU, JAMESON KA, KAJANTIE E, KERR-CONTE J, KUULASMAA T, KUUSISTO J, LOOS RJ, LUAN J, MAKRILAKIS K, MANNING AK, MARTÍNEZ-LARRAD MT, NARISU N, NASTASE MANNILA M, OHRVIK J, OSMOND C, PASCOE L, PAYNE F, SAYER AA, SENNBLAD B, SILVEIRA A, STANCÁKOVÁ A, STIRRUPS K, SWIFT AJ, SYVÄNEN AC, TUOMI T, VAN 'T HOOFT FM, WALKER M, WEEDON MN, XIE W, ZETHELIUS B, DIAGRAM CONSORTIUM, GIANT CONSORTIUM, MANUNTA P, MUTHER CONSORTIUM, CARDIOGRAM CONSORTIUM, C4D CONSORTIUM, ONGEN H, MÄLARSTIG A, HOPEWELL JC, SALEHEEN D, CHAMBERS J, PARISH S, DANESH J, KOONER J, OSTENSON CG, LIND L, COOPER CC, SERRANO-RÍOS M, FERRANNINI E, FORSEN TJ, CLARKE R, FRANZOSI MG, SEEDORF U, WATKINS H, FROGUEL P, JOHNSON P, DELOUKAS P, COLLINS FS, LAAKSO M, DERMITZAKIS ET, BOEHNKE M, MCCARTHY MI, WAREHAM NJ, GROOP L, PATTOU F, GLOYN AL, DEDOUSSIS GV, LYSSENKO V, MEIGS JB, BARROSO I, WATANABE RM, INGELSSON E, LANGENBERG C, HAMSTEN A, FLOREZ JC, Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, BOUATIA-NAJI, N, Dimas, A, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, C, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, KERR-CONTE, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, MARTÍNEZ-LARRAD, Mt, Narisu, N, NASTASE MANNILA, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, VAN 'T HOOFT, Fm, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Manunta, P, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, SERRANO-RÍOS, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, F, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, and Florez, Jc
Published: 2011

37. Verema - an affinity proteomics study to identify and translate plasma biomarkers for venous thromboembolism

Author: Bruzelius, M., Iglesias, Maria Jesus, Hong, Mun-Gwan, Tregouet, D. A., Souto, J. C., Holmström, M., Frånberg, M., Strawbridge, R. J., Sabater-Lleal, M., Sennblad, B., Silveira, A., Soria, J. M., Morange, P. E., Butler, L., Schwenk, Jochen M., Hamsten, A., Odeberg, Jacob, Bruzelius, M., Iglesias, Maria Jesus, Hong, Mun-Gwan, Tregouet, D. A., Souto, J. C., Holmström, M., Frånberg, M., Strawbridge, R. J., Sabater-Lleal, M., Sennblad, B., Silveira, A., Soria, J. M., Morange, P. E., Butler, L., Schwenk, Jochen M., Hamsten, A., and Odeberg, Jacob
Abstract: QC 20150727
Published: 2015

38. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, T.W. (Thomas W.), Justice, A.E. (Anne), Graff, M.J. (Maud J.L.), Barata, L. (Llilda), Feitosa, M.F. (Mary Furlan), Chu, S. (Su), Czajkowski, J. (Jacek), Esko, T. (Tõnu), Fall, M. (Magnus), Kilpeläinen, T.O. (Tuomas), Lu, Y. (Yingchang), Mägi, R. (Reedik), Mihailov, E. (Evelin), Pers, T.H. (Tune), Rüeger, S. (Sina), Teumer, A. (Alexander), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Heard-Costa, N.L. (Nancy), Karjalainen, J. (Juha), Lagou, V. (Vasiliki), Mahajan, A. (Anubha), Neinast, M.D. (Michael D.), Prokopenko, I. (Inga), Simino, J. (Jeannette), Teslovich, T.M. (Tanya M.), Jansen, R., Westra, H.J. (Harm-Jan), White, C.C. (Charles), Absher, D. (Devin), Ahluwalia, T.S. (Tarunveer Singh), Ahmad, S. (Shafqat), Albrecht, E. (Eva), Alves, A.C. (Alexessander Couto), Bragg-Gresham, J.L. (Jennifer L.), Craen, A.J. (Anton) de, Bis, J.C. (Joshua), Bonnefond, A. (Amélie), Boucher, G. (Gabrielle), Cadby, G. (Gemma), Cheng, Y.-C. (Yu-Ching), Chiang, C.W. (Charleston W K), Delgado, G., Demirkan, A. (Ayşe), Dueker, N. (Nicole), Eklund, N. (Niina), Eiriksdottir, G. (Gudny), Eriksson, J. (Joel), Feenstra, B. (Bjarke), Fischer, K. (Krista), Frau, F. (Francesca), Galesloot, T.E. (Tessel), Geller, F. (Frank), Goel, A. (Anuj), Gorski, M. (Mathias), Grammer, T.B. (Tanja), Gustafsson, S. (Stefan), Haitjema, S. (Saskia), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Jacobs, K.B. (Kevin), Johansson, A. (Åsa), Kaakinen, M. (Marika), Kleber, M.E. (Marcus), Lahti, J. (Jari), Leach, I.M. (Irene Mateo), Lehne, B. (Benjamin), Liu, Y. (Youfang), Lo, K.S., Lorentzon, M. (Mattias), Luan, J. (Jian'An), Madden, P.A. (Pamela), Mangino, M. (Massimo), McKnight, B. (Barbara), Medina-Gomez, C. (Carolina), Monda, K.L. (Keri), Montasser, M.E. (May E.), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Panoutsopoulou, K. (Kalliope), Pascoe, L. (Laura), Paternoster, L. (Lavinia), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rizzi, F. (Federica), Rose, L.M. (Lynda), Ryan, K.A. (Kathy A.), Salo, P. (Perttu), Sanna, S. (Serena), Scharnagl, H. (Hubert), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Southam, L. (Lorraine), Stancáková, A. (Alena), Steinthorsdottir, V. (Valgerdur), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tachmazidou, I. (Ioanna), Tanaka, T. (Toshiko), Thorleifsson, G. (Gudmar), Trompet, S. (Stella), Pervjakova, N. (Natalia), Tyrer, J.P. (Jonathan), Vandenput, L. (Liesbeth), Van Der Laan, S.W. (Sander W.), Velde, N. (Nathalie) van der, Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Verweij, N. (Niek), Vlachopoulou, E. (Efthymia), Waite, L. (Lindsay), Wang, S.R. (Sophie), Wang, Z. (Zhaoming), Wild, S.H. (Sarah), Willenborg, C. (Christina), Wilson, J.F. (James), Wong, A. (Andrew), Yang, J. (Jian), Yengo, L. (Loic), Yerges-Armstrong, L.M. (Laura), Yu, L. (Lei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Andersson, E.A. (Ehm Astrid), Bakker, S.J.L. (Stephan), Baldassarre, D. (Damiano), Banasik, K. (Karina), Barcella, M. (Matteo), Barlassina, C. (Cristina), Bellis, C. (Claire), Benaglio, P. (Paola), Blangero, J. (John), Blüher, M. (Matthias), Bonnet, F. (Fabrice), Bonnycastle, L.L. (Lori), Boyd, H.A. (Heather), Bruinenberg, M. (M.), Buchman, A.S. (Aron S.), Campbell, H. (Harry), Chen, Y.D. (Y.), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Cole, J.W. (John W.), Collins, F.S. (Francis), Geus, E.J.C. (Eco) de, Groot, L.C.P.G.M. (Lisette) de, Dimitriou, M. (Maria), Duan, J. (Jubao), Enroth, S. (Stefan), Eury, E. (Elodie), Farmaki, A.-E. (Aliki-Eleni), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gejman, P.V. (Pablo), Gigante, B. (Bruna), Glorioso, N. (Nicola), Go, A.T.J.I. (Attie), Gottesman, R.F. (Rebecca), Gräßler, J. (Jürgen), Grallert, H. (Harald), Grarup, N. (Niels), Gu, Y.-M. (Yu-Mei), Broer, L. (Linda), Ham, A.C. (Annelies), Hansen, T. (T.), Harris, T.B. (Tamara), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Heath, A.C. (Andrew), Henders, A.K. (Anjali), Hernandez, D.G. (Dena), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Hui, J. (Jennie), Husemoen, L.L. (Lise L.), Hutri-Kähönen, N. (Nina), Hysi, P.G. (Pirro), Illig, T. (Thomas), Jager, P.L. (Philip) de, Jalilzadeh, S. (Shapour), Jorgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Juonala, M. (Markus), Kanoni, S. (Stavroula), Karaleftheri, M. (Maria), Khaw, K.T., Kinnunen, L. (Leena), Kittner, T. (Thomas), Koenig, W. (Wolfgang), Kolcic, I. (Ivana), Kovacs, P. (Peter), Krarup, N.T. (Nikolaj T.), Kratzer, W. (Wolfgang), Krüger, J. (Janine), Kuh, D. (Diana), Kumari, M. (Meena), Kyriakou, T. (Theodosios), Langenberg, C. (Claudia), Lannfelt, L. (Lars), Lanzani, C. (Chiara), Lotay, V. (Vaneet), Launer, L.J. (Lenore), Leander, K. (Karin), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y.-P. (Yan-Ping), Lobbens, S. (Stéphane), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Magnusson, P.K. (Patrik), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Milani, L. (Lili), Montgomery, G.W. (Grant W.), Morris, A.P. (Andrew), Narisu, N. (Narisu), Nelis, M. (Mari), Ong, K.K. (Ken), Palotie, A. (Aarno), Perusse, L. (Louis), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Pouta, A. (Anneli), Rheinberger, M. (Myriam), Ribel-Madsen, R. (Rasmus), Richards, M. (Marcus), Rice, K.M. (Kenneth), Rice, T.K. (Treva K.), Rivolta, C. (Carlo), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Scott, W.R. (William R.), Sebert, S. (Sylvain), Sengupta, S. (Sebanti), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Silveira, A. (Angela), Slagboom, P.E. (Eline), Smit, J.H. (Jan), Sparsø, T. (Thomas), Stirrups, K. (Kathy), Stolk, R.P. (Ronald), Stringham, H.M. (Heather), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Syvänen, A.C., Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tsafantakis, E. (Emmanouil), Most, P.J. (Peter) van der, Völker, U. (Uwe), Vohl, M.-C. (Marie-Claude), Vonk, J.M. (Judith), Waldenberger, M. (Melanie), Walker, R.W. (Ryan W.), Wennauer, R. (Roman), Widen, E., Willemsen, G.A.H.M. (Gonneke), Wilsgaard, T. (Tom), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Van Dijk, S. (Suzanne), Schoor, N.M. (Natasja) van, Asselbergs, F.W. (Folkert), Bakker, P.I.W. (Paul) de, Beckmann, J.S. (Jacques), Beilby, J.P. (John), Bennett, D.A. (David A.), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Böger, C.A. (Carsten), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Bottinger, E.P. (Erwin), Bouchard, C. (Claude), Chambers, J.C. (John), Chanock, S.J. (Stephen), Chasman, D.I. (Daniel), Cucca, F. (Francesco), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evans, D., Faire, U. (Ulf) de, Farrall, M. (Martin), Ferrucci, L. (Luigi), Ford, I. (Ian), Franke, L. (Lude), Franks, P.W. (Paul), Froguel, P. (Philippe), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hall, P. (Per), Hamsten, A. (Anders), Harst, P. (Pim) van der, Hayward, C. (Caroline), Heliovaara, M. (Markku), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hofman, A. (Albert), Hu, F. (Frank), Huikuri, H.V. (Heikki), Hveem, K. (Kristian), James, A. (Alan), Jordan, J.M. (Joanne M.), Jula, A. (Antti), Kähönen, M. (Mika), Kajantie, E. (Eero), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kivimaki, M. (Mika), Knekt, P., Koistinen, H. (Heikki), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kuusisto, J. (Johanna), Maerz, W. (Winfried), Martin, N.G. (Nicholas), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Levinson, D.F. (Douglas), Kao, W.H.L. (Wen), Lokki, M.L., Mäntyselkä, P. (Pekka), Melbye, M. (Mads), Metspalu, A. (Andres), Mitchell, B.D. (Braxton), Moll, F.L. (Frans), Murray, J.C. (Jeffrey), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palmer, C. (Cameron), Pankow, J.S. (James), Pasterkamp, G. (Gerard), Pedersen, N.L. (Nancy), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Quertermous, T. (Thomas), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Rioux, J.D. (John), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Saltevo, J. (Juha), Sattar, N. (Naveed), Schunkert, H. (Heribert), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Sinisalo, J. (Juha), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Staessen, J.A. (Jan A.), Stefania, B. (Bandinelli), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tardif, J.-C. (Jean-Claude), Tremoli, E. (Elena), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Verbeek, A.L.M., Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Vitart, V. (Veronique), Völzke, H. (Henry), Vollenweider, P. (Peter), Waeber, G. (Gérard), Walker, M. (Mark), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Chakravarti, A. (Aravinda), Clegg, D.J. (Deborah J.), Cupples, L.A. (Adrienne), Gordon-Larsen, P. (Penny), Jaquish, C.E. (Cashell), Rao, D.C. (Dabeeru C.), Abecasis, G.R. (Goncalo R.), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark I.), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia M.), Heid, I.M. (Iris), North, K.E. (Kari), Borecki, I.B. (Ingrid), Kutalik, Z. (Zoltán), Loos, R.J.F. (Ruth), Winkler, T.W. (Thomas W.), Justice, A.E. (Anne), Graff, M.J. (Maud J.L.), Barata, L. (Llilda), Feitosa, M.F. (Mary Furlan), Chu, S. (Su), Czajkowski, J. (Jacek), Esko, T. (Tõnu), Fall, M. (Magnus), Kilpeläinen, T.O. (Tuomas), Lu, Y. (Yingchang), Mägi, R. (Reedik), Mihailov, E. (Evelin), Pers, T.H. (Tune), Rüeger, S. (Sina), Teumer, A. (Alexander), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Heard-Costa, N.L. (Nancy), Karjalainen, J. (Juha), Lagou, V. (Vasiliki), Mahajan, A. (Anubha), Neinast, M.D. (Michael D.), Prokopenko, I. (Inga), Simino, J. (Jeannette), Teslovich, T.M. (Tanya M.), Jansen, R., Westra, H.J. (Harm-Jan), White, C.C. (Charles), Absher, D. (Devin), Ahluwalia, T.S. (Tarunveer Singh), Ahmad, S. (Shafqat), Albrecht, E. (Eva), Alves, A.C. (Alexessander Couto), Bragg-Gresham, J.L. (Jennifer L.), Craen, A.J. (Anton) de, Bis, J.C. (Joshua), Bonnefond, A. (Amélie), Boucher, G. (Gabrielle), Cadby, G. (Gemma), Cheng, Y.-C. (Yu-Ching), Chiang, C.W. (Charleston W K), Delgado, G., Demirkan, A. (Ayşe), Dueker, N. (Nicole), Eklund, N. (Niina), Eiriksdottir, G. (Gudny), Eriksson, J. (Joel), Feenstra, B. (Bjarke), Fischer, K. (Krista), Frau, F. (Francesca), Galesloot, T.E. (Tessel), Geller, F. (Frank), Goel, A. (Anuj), Gorski, M. (Mathias), Grammer, T.B. (Tanja), Gustafsson, S. (Stefan), Haitjema, S. (Saskia), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Jacobs, K.B. (Kevin), Johansson, A. (Åsa), Kaakinen, M. (Marika), Kleber, M.E. (Marcus), Lahti, J. (Jari), Leach, I.M. (Irene Mateo), Lehne, B. (Benjamin), Liu, Y. (Youfang), Lo, K.S., Lorentzon, M. (Mattias), Luan, J. (Jian'An), Madden, P.A. (Pamela), Mangino, M. (Massimo), McKnight, B. (Barbara), Medina-Gomez, C. (Carolina), Monda, K.L. (Keri), Montasser, M.E. (May E.), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nolte, I.M. (Ilja), Panoutsopoulou, K. (Kalliope), Pascoe, L. (Laura), Paternoster, L. (Lavinia), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rizzi, F. (Federica), Rose, L.M. (Lynda), Ryan, K.A. (Kathy A.), Salo, P. (Perttu), Sanna, S. (Serena), Scharnagl, H. (Hubert), Shi, J. (Jianxin), Smith, A.V. (Albert Vernon), Southam, L. (Lorraine), Stancáková, A. (Alena), Steinthorsdottir, V. (Valgerdur), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tachmazidou, I. (Ioanna), Tanaka, T. (Toshiko), Thorleifsson, G. (Gudmar), Trompet, S. (Stella), Pervjakova, N. (Natalia), Tyrer, J.P. (Jonathan), Vandenput, L. (Liesbeth), Van Der Laan, S.W. (Sander W.), Velde, N. (Nathalie) van der, Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Verweij, N. (Niek), Vlachopoulou, E. (Efthymia), Waite, L. (Lindsay), Wang, S.R. (Sophie), Wang, Z. (Zhaoming), Wild, S.H. (Sarah), Willenborg, C. (Christina), Wilson, J.F. (James), Wong, A. (Andrew), Yang, J. (Jian), Yengo, L. (Loic), Yerges-Armstrong, L.M. (Laura), Yu, L. (Lei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Andersson, E.A. (Ehm Astrid), Bakker, S.J.L. (Stephan), Baldassarre, D. (Damiano), Banasik, K. (Karina), Barcella, M. (Matteo), Barlassina, C. (Cristina), Bellis, C. (Claire), Benaglio, P. (Paola), Blangero, J. (John), Blüher, M. (Matthias), Bonnet, F. (Fabrice), Bonnycastle, L.L. (Lori), Boyd, H.A. (Heather), Bruinenberg, M. (M.), Buchman, A.S. (Aron S.), Campbell, H. (Harry), Chen, Y.D. (Y.), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Cole, J.W. (John W.), Collins, F.S. (Francis), Geus, E.J.C. (Eco) de, Groot, L.C.P.G.M. (Lisette) de, Dimitriou, M. (Maria), Duan, J. (Jubao), Enroth, S. (Stefan), Eury, E. (Elodie), Farmaki, A.-E. (Aliki-Eleni), Forouhi, N.G. (Nita), Friedrich, N. (Nele), Gejman, P.V. (Pablo), Gigante, B. (Bruna), Glorioso, N. (Nicola), Go, A.T.J.I. (Attie), Gottesman, R.F. (Rebecca), Gräßler, J. (Jürgen), Grallert, H. (Harald), Grarup, N. (Niels), Gu, Y.-M. (Yu-Mei), Broer, L. (Linda), Ham, A.C. (Annelies), Hansen, T. (T.), Harris, T.B. (Tamara), Hartman, C.A. (Catharina A.), Hassinen, M. (Maija), Hastie, N. (Nick), Hattersley, A.T. (Andrew), Heath, A.C. (Andrew), Henders, A.K. (Anjali), Hernandez, D.G. (Dena), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Hui, J. (Jennie), Husemoen, L.L. (Lise L.), Hutri-Kähönen, N. (Nina), Hysi, P.G. (Pirro), Illig, T. (Thomas), Jager, P.L. (Philip) de, Jalilzadeh, S. (Shapour), Jorgensen, T. (Torben), Jukema, J.W. (Jan Wouter), Juonala, M. (Markus), Kanoni, S. (Stavroula), Karaleftheri, M. (Maria), Khaw, K.T., Kinnunen, L. (Leena), Kittner, T. (Thomas), Koenig, W. (Wolfgang), Kolcic, I. (Ivana), Kovacs, P. (Peter), Krarup, N.T. (Nikolaj T.), Kratzer, W. (Wolfgang), Krüger, J. (Janine), Kuh, D. (Diana), Kumari, M. (Meena), Kyriakou, T. (Theodosios), Langenberg, C. (Claudia), Lannfelt, L. (Lars), Lanzani, C. (Chiara), Lotay, V. (Vaneet), Launer, L.J. (Lenore), Leander, K. (Karin), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y.-P. (Yan-Ping), Lobbens, S. (Stéphane), Luben, R.N. (Robert), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Magnusson, P.K. (Patrik), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Milani, L. (Lili), Montgomery, G.W. (Grant W.), Morris, A.P. (Andrew), Narisu, N. (Narisu), Nelis, M. (Mari), Ong, K.K. (Ken), Palotie, A. (Aarno), Perusse, L. (Louis), Pichler, I. (Irene), Pilia, M.G. (Maria Grazia), Pouta, A. (Anneli), Rheinberger, M. (Myriam), Ribel-Madsen, R. (Rasmus), Richards, M. (Marcus), Rice, K.M. (Kenneth), Rice, T.K. (Treva K.), Rivolta, C. (Carlo), Salomaa, V. (Veikko), Sanders, A.R. (Alan), Sarzynski, M.A. (Mark A.), Scholtens, S. (Salome), Scott, R.A. (Robert), Scott, W.R. (William R.), Sebert, S. 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(Eric), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Bottinger, E.P. (Erwin), Bouchard, C. (Claude), Chambers, J.C. (John), Chanock, S.J. (Stephen), Chasman, D.I. (Daniel), Cucca, F. (Francesco), Cusi, D. (Daniele), Dedoussis, G.V. (George), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evans, D., Faire, U. (Ulf) de, Farrall, M. (Martin), Ferrucci, L. (Luigi), Ford, I. (Ian), Franke, L. (Lude), Franks, P.W. (Paul), Froguel, P. (Philippe), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Grönberg, H. (Henrik), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hall, P. (Per), Hamsten, A. (Anders), Harst, P. (Pim) van der, Hayward, C. (Caroline), Heliovaara, M. (Markku), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hofman, A. (Albert), Hu, F. (Frank), Huikuri, H.V. (Heikki), Hveem, K. (Kristian), James, A. (Alan), Jordan, J.M. (Joanne M.), Jula, A. (Antti), Kähönen, M. (Mika), Kajantie, E. (Eero), Kathiresan, S. (Sekar), Kiemeney, L.A.L.M. (Bart), Kivimaki, M. (Mika), Knekt, P., Koistinen, H. (Heikki), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kuusisto, J. (Johanna), Maerz, W. (Winfried), Martin, N.G. (Nicholas), Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), Lettre, G. (Guillaume), Levinson, D.F. (Douglas), Kao, W.H.L. (Wen), Lokki, M.L., Mäntyselkä, P. (Pekka), Melbye, M. (Mads), Metspalu, A. (Andres), Mitchell, B.D. (Braxton), Moll, F.L. (Frans), Murray, J.C. (Jeffrey), Musk, A.W. (Arthur), Nieminen, M.S. (Markku), Njølstad, I. (Inger), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), Palmer, C. (Cameron), Pankow, J.S. (James), Pasterkamp, G. (Gerard), Pedersen, N.L. (Nancy), Pedersen, O. (Oluf), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Quertermous, T. (Thomas), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rauramaa, R. (Rainer), Ridker, P.M. (Paul), Rioux, J.D. (John), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Saltevo, J. (Juha), Sattar, N. (Naveed), Schunkert, H. (Heribert), Schwarz, P.E.H. (Peter), Shuldiner, A.R. (Alan), Sinisalo, J. (Juha), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Spector, T.D. (Timothy), Staessen, J.A. (Jan A.), Stefania, B. (Bandinelli), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tardif, J.-C. (Jean-Claude), Tremoli, E. (Elena), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Verbeek, A.L.M., Vermeulen, S.H.H.M. (Sita), Viikari, J. (Jorma), Vitart, V. (Veronique), Völzke, H. (Henry), Vollenweider, P. (Peter), Waeber, G. (Gérard), Walker, M. (Mark), Wallaschofski, H. (Henri), Wareham, N.J. (Nick), Watkins, H. (Hugh), Zeggini, E. (Eleftheria), Chakravarti, A. (Aravinda), Clegg, D.J. (Deborah J.), Cupples, L.A. (Adrienne), Gordon-Larsen, P. (Penny), Jaquish, C.E. (Cashell), Rao, D.C. (Dabeeru C.), Abecasis, G.R. (Goncalo R.), Assimes, T.L. (Themistocles), Barroso, I.E. (Inês), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Groop, L. (Leif), Hunter, D. (David), Ingelsson, E. (Erik), Kaplan, R.C. (Robert), McCarthy, M.I. (Mark I.), Mohlke, K.L. (Karen), O´Connell, J.R., Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Hirschhorn, J.N. (Joel), Lindgren, C.M. (Cecilia M.), Heid, I.M. (Iris), North, K.E. (Kari), Borecki, I.B. (Ingrid), Kutalik, Z. (Zoltán), and Loos, R.J.F. (Ruth)
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for B
Published: 2015
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39. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author: Wessel, J. (Jennifer), Chu, A.Y. (Audrey Y), Willems, S.M. (Sara), Wang, S. (Shuai), Yaghootkar, H. (Hanieh), Brody, J.A. (Jennifer A.), Dauriz, M. (Marco), Hivert, M.-F. (Marie-France), Raghavan, S. (Sridharan), Lipovich, L. (Leonard), Hidalgo, B. (Bertha), Fox, K. (Keolu), Huffman, J.E. (Jennifer), An, P. (Ping), Lu, Y. (Yingchang), Rasmussen-Torvik, L.J. (Laura), Grarup, N. (Niels), Ehm, M.G. (Margaret G), L. Li, Baldridge, A.S. (Abigail S), Stancáková, A. (Alena), Abrol, R. (Ravinder), Besse, C. (Céline), Boland, A. (Anne), Bork-Jensen, J. (Jette), Fornage, M. (Myriam), Freitag, C.M. (Christine), Garcia, M. (Melissa), Guo, X. (Xiuqing), Hara, K. (Kazuo), Isaacs, A. (Aaron), Jakobsdottir, M. (Margret), Lange, L.A. (Leslie), Layton, J.C. (Jill C), Li, M. (Man), Zhao, J.H. (Jing Hua), Meidtner, K. (Karina), Morrison, A.C. (Alanna), Nalls, M.A. (Michael), Peters, M.J. (Marjolein), Sabater-Lleal, M. (Maria), Schurmann, C. (Claudia), Silveira, A. (Angela), Smith, A.V. (Davey), Southam, L. (Lorraine), Stoiber, M.H. (Marcus H), Strawbridge, R.J. (Rona), Taylor, K.D. (Kent), Varga, T.V. (Tibor V.), Allin, K.H. (Kristine H), Amin, N. (Najaf), Aponte, J.L. (Jennifer L), Aung, T. (Tin), Barbieri, C. (Caterina), Bihlmeyer, N.A. (Nathan A.), Boehnke, M. (Michael), Bombieri, C. (Cristina), Bowden, D.W. (Donald), Burns, S.M. (Sean M), Chen, Y. (Yuning), Chen, Y.-D. (Yii-Deri), Cheng, C-Y. (Ching-Yu), Correa, D.D., Czajkowski, J. (Jacek), Dehghan, A. (Abbas), Ehret, G.B. (Georg), Eiriksdottir, G. (Gudny), Escher, S.A. (Stefan A), Farmaki, A.-E. (Aliki-Eleni), Frånberg, M. (Mattias), Gambaro, G. (Giovanni), Giulianini, F. (Franco), Goddard, W.A. (William A), Goel, A. (Anuj), Gottesman, R.F. (Rebecca), Grove, M.L. (Megan), Gustafsson, S. (Stefan), Hai, Y. (Yang), Hallmans, G. (Göran), Heo, J. (Jiyoung), Hoffmann, P. (Per), Ikram, M.K. (Kamran), Jensen, R.A. (Richard), Jørgensen, M.E. (Marit), Jorgensen, T. (Torben), Karaleftheri, M. (Maria), Khor, C.C., Kirkpatrick, A. (Andrea), Kraja, A. (Aldi), Kuusisto, J. (Johanna), Lange, E.M. (Ethan), Lee, I.T., Lee, W.-J. (Wen-Jane), Leong, A. (Aaron), Liao, J. (Jie), Liu, C. (Chunyu), Liu, Y. (YongMei), Lindgren, C.M. (Cecilia), Linneberg, A. (Allan), Malerba, G. (Giovanni), Mamakou, V. (Vasiliki), Marouli, E. (Eirini), Maruthur, N.M. (Nisa M), Matchan, A. (Angela), McKean-Cowdin, R. (Roberta), McLeod, O. (Olga), Metcalf, G.A. (Ginger A.), Mohlke, K.L. (Karen), Muzny, D. (Donna), Ntalla, I. (Ioanna), Palmer, N.D. (Nicholette), Pasko, D. (Dorota), Peter, A. (Andreas), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rice, K.M. (Kenneth), Sala, C. (Cinzia), Sennblad, B. (Bengt), Serafetinidis, I. (Ioannis), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Speliotes, E.K. (Elizabeth), Stahl, E.A. (Eli), Stirrups, K. (Kathy), Tentolouris, N. (Nikos), Thanopoulou, A. (Anastasia), Torres, M. (Mina), Traglia, M. (Michela), Tsafantakis, E. (Emmanouil), Javad, S. (Sundas), Yanek, L.R. (Lisa), Zengini, E. (Eleni), Becker, D.M. (Diane), Bis, J.C. (Joshua), Brown, J.B. (James B), Cupples, L.A. (Adrienne), Hansen, T. (T.), Ingelsson, E. (Erik), Karter, A.J. (Andrew J), Lorenzo, C. (Carlos), Mathias, J. (Jasmine), Norris, J.M. (Jill M), Peloso, G.M. (Gina), Sheu, W.H.-H. (Wayne H.-H.), Toniolo, D. (Daniela), Vaidya, D. (Dhananjay), Varma, R. (Rohit), Wagenknecht, L.E. (Lynne), Boeing, H. (Heiner), Bottinger, E.P. (Erwin P.), Dedoussis, G.V. (George), Deloukas, P. (Panagiotis), Ferrannini, E. (Ele), Franco, O.H. (Oscar), Franks, P.W. (Paul), Gibbs, R.A. (Richard A), Gudnason, V. (Vilmundur), Hamsten, A. (Anders), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), Hofman, A. (Albert), Jansson, J.-H. (Jan-Håkan), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Levy, D. (Daniel), Oostra, B.A. (Ben), O'Donnell, C.J. (Christopher J.), O'Rahilly, S. (Stephen), Padmanabhan, S. (Sandosh), Pankow, J.S. (James), Polasek, O. 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Published: 2015
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40. New genetic loci link adipose and insulin biology to body fat distribution.

Author: ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., 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Eklund, N., Erdos, M.R., Eury, E., Friedrich, N., Garcia, M.E., Giedraitis, V., Go, A.S., Golay, A., Grammer, T.B., Gräßler, J., Grewal, J., Groves, C.J., Hartman, C.A., Hassinen, M., Herzig, K.H., Helmer, Q., Hillege, H.L., Holmen, O., Hunt, S.C., Ittermann, T., James, A.L., Johansson, I., Juliusdottir, T., Kalafati, I.P., Kinnunen, L., Kooner, I.K., Lee, N.R., Lichtner, P., Lobbens, S., Magnusson, P.K., McArdle, W.L., Menni, C., Merger, S., Milani, L., Mills, R., Monda, K.L., Mooijaart, S.P., Mühleisen, T.W., Mulas, A., Nalls, M.A., Glorioso, N., Nolte, I.M., Rayner, N.W., Renstrom, F., Ried, J.S., Robertson, N.R., Rose, L.M., Scholtens, S., Seufferlein, T., Sitlani, C.M., Vernon Smith, A., Stringham, H.M., Sundström, J., Swertz, M.A., Swift, A.J., Syvänen, A.C., Tayo, B.O., Tomaschitz, A., Troffa, C., van Oort, F.V., Vonk, J.M., Waite, L.L., Wennauer, R., Wojczynski, M.K., Zhang, Q., Hua Zhao, J., Brennan, E.P., Choi, M., Gharavi, A.G., Hedman, Å.K., Hivert, M.F., Huang, J., Karpe, F., Kiryluk, K., Liang, L., Lifton, R.P., Ma, B., McKnight, A.J., McPherson, R., Min, J.L., Moffatt, M.F., Montgomery, G.W., Murabito, J.M., Nicholson, G., Nyholt, D.R., Olsson, C., Perry, J.R., Reinmaa, E., Salem, R.M., Schadt, E.E., Scott, R.A., Vallejo, E.E., Westra, H.J., Zondervan, K.T., Bakker, S.J., Beilby, J., Bergman, R.N., Blangero, J., Brown, M.J., Chines, P.S., Collins, F.S., Crawford, D.C., de Geus, E.J., Erbel, R., Eriksson, J.G., Ferrannini, E., Forouhi, N.G., Franco, O.H., Gansevoort, R.T., Haiman, C.A., Harris, T.B., Hattersley, A.T., Heliövaara, M., Hicks, A.A., Hingorani, A.D., Hoffmann, W., Humphries, S.E., Jarvelin, M.R., Johansen, B., Jousilahti, P., Jula, A.M., Keinanen-Kiukaanniemi, S.M., Kooner, J.S., Kraja, A.T., Lakka, T.A., Le Marchand, L., Lyssenko, V., Männistö, S., Marette, A., Matise, T.C., McKenzie, C.A., Musk, A.W., Möhlenkamp, S., Morris, A.D., Oldehinkel, A.J., Ong, K.K., Palmer, L.J., Penninx, B.W., Pramstaller, P.P., Raitakari, O.T., Rankinen, T., Rao, D.C., Rice, T.K., Ridker, P.M., Ritchie, M.D., Samani, N.J., Sarzynski, M.A., Schwarz, P.E., Shuldiner, A.R., Staessen, J.A., Steinthorsdottir, V., Stolk, R.P., Strauch, K., Tremblay, A., Vohl, M.C., Wilson, J.F., Witteman, J.C., Adair, L.S., Boehm, B.O., Bornstein, S.R., Bouchard, C., Cauchi, S., Caulfield, M.J., Chambers, J.C., Chasman, D.I., Cooper, R.S., Grabe, H.J., Jöckel, K.H., Munroe, P.B., Oostra, B.A., Palmer, C.N., Pedersen, N.L., Pérusse, L., Saaristo, T.E., Slagboom, P.E., Spector, T.D., Uitterlinden, A.G., Veronesi, G., Walker, M., Wareham, N.J., Wichmann, H.E., Abecasis, G.R., Assimes, T.L., Berndt, S.I., Borecki, I.B., Frayling, T.M., Groop, L.C., Hunter, D.J., Kaplan, R.C., O'Connell, J.R., Strachan, D.P., van Duijn, C.M., Willer, C.J., Visscher, P.M., Yang, J., Hirschhorn, J.N., Zillikens, M.C., McCarthy, M.I., Speliotes, E.K., North, K.E., Fox, C.S., Franks, P.W., Heid, I.M., Loos, R.J., Cupples, L.A., Morris, A.P., Lindgren, C.M., and Mohlke, K.L.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

41. Directional dominance on stature and cognition in diverse human populations.

Author: BioBank Japan, Project, Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., Wilson, J.F., BioBank Japan, Project, Joshi, P.K., Esko, T., Mattsson, H., Eklund, N., Gandin, I., Nutile, T., Jackson, A.U., Schurmann, C., Smith, A.V., Zhang, W., Okada, Y., Stančáková, A., Faul, J.D., Zhao, W., Bartz, T.M., Concas, M.P., Franceschini, N., Enroth, S., Vitart, V., Trompet, S., Guo, X., Chasman, D.I., O'Connel, J.R., Corre, T., Nongmaithem, S.S., Chen, Y., Mangino, M., Ruggiero, D., Traglia, M., Farmaki, A.E., Kacprowski, T., Bjonnes, A., van der Spek, A., Wu, Y., Giri, A.K., Yanek, L.R., Wang, L., Hofer, E., Rietveld, C.A., McLeod, O., Cornelis, M.C., Pattaro, C., Verweij, N., Baumbach, C., Abdellaoui, A., Warren, H.R., Vuckovic, D., Mei, H., Bouchard, C., Perry, J.R., Cappellani, S., Mirza, S.S., Benton, M.C., Broeckel, U., Medland, S.E., Lind, P.A., Malerba, G., Drong, A., Yengo, L., Bielak, L.F., Zhi, D., van der Most, P.J., Shriner, D., Mägi, R., Hemani, G., Karaderi, T., Wang, Z., Liu, T., Demuth, I., Zhao, J.H., Meng, W., Lataniotis, L., van der Laan, S.W., Bradfield, J.P., Wood, A.R., Bonnefond, A., Ahluwalia, T.S., Hall, L.M., Salvi, E., Yazar, S., Carstensen, L., de Haan, H.G., Abney, M., Afzal, U., Allison, M.A., Amin, N., Asselbergs, F.W., Bakker, S.J., Barr, R.G., Baumeister, S.E., Benjamin, D.J., Bergmann, S., Boerwinkle, E., Bottinger, E.P., Campbell, A., Chakravarti, A., Chan, Y., Chanock, S.J., Chen, C., Chen, Y.D., Collins, F.S., Connell, J., Correa, A., Cupples, L.A., Smith, G.D., Davies, G., Dörr, M., Ehret, G., Ellis, S.B., Feenstra, B., Feitosa, M.F., Ford, I., Fox, C.S., Frayling, T.M., Friedrich, N., Geller, F., Scotland, G., Gillham-Nasenya, I., Gottesman, O., Graff, M., Grodstein, F., Gu, C., Haley, C., Hammond, C.J., Harris, S.E., Harris, T.B., Hastie, N.D., Heard-Costa, N.L., Heikkilä, K., Hocking, L.J., Homuth, G., Hottenga, J.J., Huang, J., Huffman, J.E., Hysi, P.G., Ikram, M.A., Ingelsson, E., Joensuu, A., Johansson, Å., Jousilahti, P., Jukema, J.W., Kähönen, M., Kamatani, Y., Kanoni, S., Kerr, S.M., Khan, N.M., Koellinger, P., Koistinen, H.A., Kooner, M.K., Kubo, M., Kuusisto, J., Lahti, J., Launer, L.J., Lea, R.A., Lehne, B., Lehtimäki, T., Liewald, D.C., Lind, L., Loh, M., Lokki, M.L., London, S.J., Loomis, S.J., Loukola, A., Lu, Y., Lumley, T., Lundqvist, A., Männistö, S., Marques-Vidal, P., Masciullo, C., Matchan, A., Mathias, R.A., Matsuda, K., Meigs, J.B., Meisinger, C., Meitinger, T., Menni, C., Mentch, F.D., Mihailov, E., Milani, L., Montasser, M.E., Montgomery, G.W., Morrison, A., Myers, R.H., Nadukuru, R., Navarro, P., Nelis, M., Nieminen, M.S., Nolte, I.M., O'Connor, G.T., Ogunniyi, A., Padmanabhan, S., Palmas, W.R., Pankow, J.S., Patarcic, I., Pavani, F., Peyser, P.A., Pietilainen, K., Poulter, N., Prokopenko, I., Ralhan, S., Redmond, P., Rich, S.S., Rissanen, H., Robino, A., Rose, L.M., Rose, R., Sala, C., Salako, B., Salomaa, V., Sarin, A.P., Saxena, R., Schmidt, H., Scott, L.J., Scott, W.R., Sennblad, B., Seshadri, S., Sever, P., Shrestha, S., Smith, B.H., Smith, J.A., Soranzo, N., Sotoodehnia, N., Southam, L., Stanton, A.V., Stathopoulou, M.G., Strauch, K., Strawbridge, R.J., Suderman, M.J., Tandon, N., Tang, S.T., Taylor, K.D., Tayo, B.O., Töglhofer, A.M., Tomaszewski, M., T?ernikova N., Tuomilehto, J., Uitterlinden, A.G., Vaidya, D., van Hylckama Vlieg, A., van Setten, J., Vasankari, T., Vedantam, S., Vlachopoulou, E., Vozzi, D., Vuoksimaa, E., Waldenberger, M., Ware, E.B., Wentworth-Shields, W., Whitfield, J.B., Wild, S., Willemsen, G., Yajnik, C.S., Yao, J., Zaza, G., Zhu, X., Salem, R.M., Melbye, M., Bisgaard, H., Samani, N.J., Cusi, D., Mackey, D.A., Cooper, R.S., Froguel, P., Pasterkamp, G., Grant, S.F., Hakonarson, H., Ferrucci, L., Scott, R.A., Morris, A.D., Palmer, C.N., Dedoussis, G., Deloukas, P., Bertram, L., Lindenberger, U., Berndt, S.I., Lindgren, C.M., Timpson, N.J., Tönjes, A., Munroe, P.B., Sørensen, T.I., Rotimi, C.N., Arnett, D.K., Oldehinkel, A.J., Kardia, S.L., Balkau, B., Gambaro, G., Morris, A.P., Eriksson, J.G., Wright, M.J., Martin, N.G., Hunt, S.C., Starr, J.M., Deary, I.J., Griffiths, L.R., Tiemeier, H., Pirastu, N., Kaprio, J., Wareham, N.J., Pérusse, L., Wilson, J.G., Girotto, G., Caulfield, M.J., Raitakari, O., Boomsma, D.I., Gieger, C., van der Harst, P., Hicks, A.A., Kraft, P., Sinisalo, J., Knekt, P., Johannesson, M., Magnusson, P.K., Hamsten, A., Schmidt, R., Borecki, I.B., Vartiainen, E., Becker, D.M., Bharadwaj, D., Mohlke, K.L., Boehnke, M., van Duijn, C.M., Sanghera, D.K., Teumer, A., Zeggini, E., Metspalu, A., Gasparini, P., Ulivi, S., Ober, C., Toniolo, D., Rudan, I., Porteous, D.J., Ciullo, M., Spector, T.D., Hayward, C., Dupuis, J., Loos, R.J., Wright, A.F., Chandak, G.R., Vollenweider, P., Shuldiner, A.R., Ridker, P.M., Rotter, J.I., Sattar, N., Gyllensten, U., North, K.E., Pirastu, M., Psaty, B.M., Weir, D.R., Laakso, M., Gudnason, V., Takahashi, A., Chambers, J.C., Kooner, J.S., Strachan, D.P., Campbell, H., Hirschhorn, J.N., Perola, M., Pola?ek O., and Wilson, J.F.
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolu
Published: 2015

42. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), Mohlke, K.L. (Karen), Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), and Mohlke, K.L. (Karen)
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10-8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015
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43. Rare and low-frequency variants and their association with plasma levels of fibrinogen, FVII, FVIII, and vWF

Author: Huffman, J.E. (Jennifer), Vries, P.S. (Paul) de, Morrison, A.C. (Alanna), Sabater-Lleal, M. (Maria), Kacprowski, T. (Tim), Auer, P. (Paul), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel), Chen, M.-H. (Ming-Huei), Guo, X. (Xiuqing), Lin, L.-A. (Li-An), Marioni, R.E. (Riccardo), Müller-Nurasyid, M. (Martina), Yanek, L.R. (Lisa), Pankratz, V.S. (Shane), Grove, M.L. (Megan L.), Maat, M.P.M. (Moniek) de, Cushman, M. (Mary Ann), Wiggins, K.L. (Kerri), Qi, L. (Lihong), Sennblad, B. (Bengt), Harris, S.E. (Sarah), Polasek, O. (Ozren), Riess, H. (Helene), Rivadeneira Ramirez, F. (Fernando), Rose, L.M. (Lynda), Goel, A. (Anuj), Taylor, K.D. (Kent D.), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Yao, J. (Jiefen), Tang, W. (Weihong), Levy, D. (Daniel), Waldenberger, M. (Melanie), Becker, D.M. (Diane), Folsom, A.R. (Aaron), Giulianini, F. (Franco), Greinacher, A. (Andreas), Hofman, A. (Albert), Huang, C.-C. (Chiang-Ching), Kooperberg, C. (Charles), Silveira, A. (Angela), Starr, J.M. (John), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Wright, A. (Alan), McKnight, B. (Barbara), Franco, O.H. (Oscar), Zakai, N.A. (Neil), Mathias, J. (Jasmine), Psaty, B.M. (Bruce), Ridker, P.M. (Paul), Tofler, G.H. (Geoffrey), Völker, U. (Uwe), Watkins, H. (Hugh), Fornage, M. (Myriam), Hamsten, A. (Anders), Deary, I.J. (Ian), Boerwinkle, E.A. (Eric), Koenig, W. (Wolfgang), Rotter, J.I. (Jerome I.), Hayward, C. (Caroline), Dehghan, A. (Abbas), Reiner, A. (Alexander), O'Donnell, C.J. (Christopher), Smith, N.L. (Nicholas), Huffman, J.E. (Jennifer), Vries, P.S. (Paul) de, Morrison, A.C. (Alanna), Sabater-Lleal, M. (Maria), Kacprowski, T. (Tim), Auer, P. (Paul), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel), Chen, M.-H. (Ming-Huei), Guo, X. (Xiuqing), Lin, L.-A. (Li-An), Marioni, R.E. (Riccardo), Müller-Nurasyid, M. (Martina), Yanek, L.R. (Lisa), Pankratz, V.S. (Shane), Grove, M.L. (Megan L.), Maat, M.P.M. (Moniek) de, Cushman, M. (Mary Ann), Wiggins, K.L. (Kerri), Qi, L. (Lihong), Sennblad, B. (Bengt), Harris, S.E. (Sarah), Polasek, O. (Ozren), Riess, H. (Helene), Rivadeneira Ramirez, F. (Fernando), Rose, L.M. (Lynda), Goel, A. (Anuj), Taylor, K.D. (Kent D.), Teumer, A. (Alexander), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Yao, J. (Jiefen), Tang, W. (Weihong), Levy, D. (Daniel), Waldenberger, M. (Melanie), Becker, D.M. (Diane), Folsom, A.R. (Aaron), Giulianini, F. (Franco), Greinacher, A. (Andreas), Hofman, A. (Albert), Huang, C.-C. (Chiang-Ching), Kooperberg, C. (Charles), Silveira, A. (Angela), Starr, J.M. (John), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Wright, A. (Alan), McKnight, B. (Barbara), Franco, O.H. (Oscar), Zakai, N.A. (Neil), Mathias, J. (Jasmine), Psaty, B.M. (Bruce), Ridker, P.M. (Paul), Tofler, G.H. (Geoffrey), Völker, U. (Uwe), Watkins, H. (Hugh), Fornage, M. (Myriam), Hamsten, A. (Anders), Deary, I.J. (Ian), Boerwinkle, E.A. (Eric), Koenig, W. (Wolfgang), Rotter, J.I. (Jerome I.), Hayward, C. (Caroline), Dehghan, A. (Abbas), Reiner, A. (Alexander), O'Donnell, C.J. (Christopher), and Smith, N.L. (Nicholas)
Abstract: Fibrinogen, coagulation factor VII (FVII), and factor VIII (FVIII) and its carrier von Willebrand factor (vWF) play key roles in hemostasis. Previously identified common variants explain only a small fraction of the trait heritabilities, and additional variations may be explained by associations with rarer variants with larger effects. The aim of this study was to identify low-frequency (minor allele frequency [MAF] ≥0.01 and <0.05) and rare (MAF <0.01) variants that influence plasma concentrations of these 4 hemostatic factors by meta-analyzing exome chip data from up to 76 000 participants of 4 ancestries. We identified 12 novel associations of low-frequency (n = 2) and rare (n = 10) variants across the fibrinogen, FVII, FVIII, and vWF traits that were independent of previously identified associations. Novel loci were found within previously reported genes and had effect sizes much larger than and independent of previously identified
Published: 2015
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44. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, P.K. (Peter), Esko, T. (Tõnu), Mattsson, H. (Hannele), Eklund, N. (Niina), Gandin, I. (Ilaria), Nutile, T., Jackson, A.U. (Anne), Schurmann, C. (Claudia), Smith, A.V. (Davey), Zhang, W. (Weihua), Okada, Y. (Yukinori), Stancáková, A. (Alena), Faul, J.D. (Jessica D.), Zhao, W. (Wei), Bartz, T.M. (Traci M.), Concas, M.P. (Maria Pina), Franceschini, N. (Nora), Enroth, S. (Stefan), Vitart, V. (Veronique), Trompet, S. (Stella), Guo, X. (Xiuqing), Chasman, D.I. (Daniel), O'Connel, J.R. (Jeffrey R.), Corre, T. (Tanguy), Nongmaithem, S.S. (Suraj S.), Chen, Y. (Yuning), Mangino, M. (Massimo), Ruggiero, D., Traglia, M. (Michela), Farmaki, A.-E. (Aliki-Eleni), Kacprowski, T. (Tim), Bjonnes, A. (Andrew), Spek, A. (Ashley) van der, Wu, Y. (Ying), Giri, A.K. (Anil K.), Yanek, L.R. (Lisa), Wang, L. (Lihua), Hofer, E. (Edith), Rietveld, C.A. (Niels), McLeod, O. (Olga), Cornelis, M. (Marilyn), Pattaro, C. (Cristian), Verweij, N. (Niek), Baumbach, C. (Clemens), Abdellaoui, A. (Abdel), Warren, H. (Helen), Vuckovic, D. (Dragana), Mei, H. (Hao), Bouchard, C. (Claude), Perry, J.R.B. (John), Cappellani, S. (Stefania), Mirza, S.S. (Saira), Benton, M.C. (Miles C.), Broeckel, U. (Ulrich), Medland, S.E. (Sarah), Lind, P.A. (Penelope), Malerba, G. (Giovanni), Drong, A. (Alexander), Yengo, L. (Loic), Bielak, L.F. (Lawrence F.), Zhi, D. (Degui), Most, P.J. (Peter) van der, Shriner, D. (Daniel), Mägi, R. (Reedik), Hemani, G., Karaderi, T. (Tugce), Wang, Z. (Zhaoming), Liu, T. (Tian), Demuth, I. (Ilja), Zhao, J.H. (Jing Hua), Meng, W. (Weihua), Lataniotis, L. (Lazaros), Van Der Laan, S.W. (Sander W.), Bradfield, J.P. (Jonathan), Wood, A.R. (Andrew), Bonnefond, A. (Amélie), Ahluwalia, T.S. (Tarunveer Singh), Hall, L.M. (Leanne M.), Salvi, E. (Erika), Yazar, S. (Seyhan), Carstensen, L. (Lisbeth), Haan, H.G. (Hugoline) de, Abney, M. (Mark), Afzal, U. (Uzma), Allison, M.A. (Matthew), Amin, N. (Najaf), Asselbergs, F.W. (Folkert W.), Bakker, S.J.L. (Stephan), Barr, R.G. (Graham), Baumeister, S.E. (Sebastian), Benjamin, D.J. (Daniel J.), Bergmann, S. (Sven), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Campbell, A. (Archie), Chakravarti, A. (Aravinda), Chan, Y. (Yingleong), Chanock, S.J. (Stephen), Chen, C. (Constance), Chen, Y.-D.I. (Y.-D. Ida), Collins, F.S. (Francis), Connell, J. (John), Correa, A. (Adolfo), Cupples, L.A. (Adrienne), Davies, G. (Gail), Dörr, M. (Marcus), Ehret, G.B. (Georg), Ellis, S.B. (Stephen B.), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Ford, I., Fox, C.S. (Caroline), Frayling, T.M. (Timothy), Friedrich, N. (Nele), Geller, F. (Frank), Scotland, G. (Generation), Gillham-Nasenya, I. (Irina), Gottesman, R.F. (Rebecca), Graff, M.J. (Maud J.L.), Grodstein, F. (Francine), Gu, C. (Charles), Haley, C. (Chris), Hammond, C.J. (Christopher), Harris, S.E. (Sarah), Harris, T.B. (Tamara), Hastie, N. (Nick), Heard-Costa, N.L. (Nancy), Heikkilä, K. (Kauko), Hocking, L.J. (Lynne), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huffman, J.E. (Jennifer), Hysi, P.G. (Pirro), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Joensuu, A. (Anni), Johansson, A. (Åsa), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanoni, S. (Stavroula), Kerr, S.M. (Shona), Khan, N.M. (Nazir M.), Koellinger, Ph.D. (Philipp), Koistinen, H.A. (Heikki A.), Kooner, M.K. (Manraj K.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lahti, J. (Jari), Launer, L.J. (Lenore), Lea, R.A. (Rodney A.), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Lind, L. (Lars), Loh, M. (Marie), Lokki, M.L., London, S.J. (Stephanie J.), Loomis, S.J. (Stephanie J.), Loukola, A. (Anu), Lu, Y. (Yingchang), Lumley, T. (Thomas), Lundqvist, A. (Annamari), Männistö, S. (Satu), Marques-Vidal, P. (Pedro), Masciullo, C. (Corrado), Matchan, A. (Angela), Mathias, J. (Jasmine), Matsuda, K. (Koichi), Meigs, J.B. (James), Meisinger, C. (Christa), Meitinger, T. (Thomas), Menni, C. (Cristina), Mentch, F.D. (Frank), Mihailov, E. (Evelin), Milani, L. (Lili), Montasser, M.E. (May E.), Montgomery, G.W. (Grant), Morrison, A.C. (Alanna), Myers, R.H. (Richard), Nadukuru, R. (Rajiv), Navarro, P. (Pau), Nalis, M. (Mari), Nieminen, M.S. (Markku S.), Nolte, I.M. (Ilja M.), O'Connor, G.T. (George), Ogunniyi, A. (Adesola), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Pankow, J.S. (James), Patarcic, I. (Inga), Pavani, F. (Francesca), Peyser, P.A. (Patricia A.), Pietilainen, K.H. (Kirsi Hannele), Poulter, N.R. (Neil), Prokopenko, I. (Inga), Ralhan, S. (Sarju), Redmond, P. (Paul), Rich, S.S. (Stephen S.), Rissanen, H. (Harri), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rose, R.J. (Richard J.), Sala, C. (Cinzia), Salako, B. (Babatunde), Salomaa, V. (Veikko), Sarin, A.-P., Saxena, R. (Richa), Schmidt, R. (Reinhold), Scott, L.J. (Laura), Scott, W.R. (William R.), Sennblad, B. (Bengt), Seshadri, S. (Sudha), Sever, P. (Peter), Shrestha, S. (Smeeta), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Sotoodehnia, N. (Nona), Southam, L. (Lorraine), Stanton, A. (Alice), Stathopoulou, M.G. (Maria G), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Suderman, M.J. (Matthew J.), Tandon, N. (Nikhil), Tang, S.-T. (Sian-Tsun), Taylor, K.D. (Kent D.), Tayo, B. (Bamidele), Töglhofer, A.M. (Anna Maria), Tomaszewski, M. (Maciej), Tsernikova, N. (Natalia), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Hylckama Vlieg, A. (Astrid) van, Setten, J. (Jessica) van, Vasankari, T. (Tuula), Vedantam, S. (Sailaja), Vlachopoulou, E. (Efthymia), Vozzi, D. (Diego), Vuoksimaa, E. (Eero), Waldenberger, M. (Melanie), Ware, E.B. (Erin B.), Wentworth-Shields, W. (William), Whitfield, J. (John), Wild, S. (Sarah), Willemsen, G.A.H.M. (Gonneke), Yajnik, C.S. (Chittaranjan S.), Yao, J. (Jie), Zaza, G. (Gianluigi), Zhu, X. (Xiaofeng), Salem, R.M. (Rany), Melbye, M. (Mads), Bisgaard, H. (Hans), Samani, N.J. (Nilesh), Cusi, D. (Daniele), Mackey, D.A. (David A.), Cooper, R.S. (Richard S.), Froguel, P. (Philippe), Pasterkamp, G. (Gerard), Grant, S.F.A. (Struan F.A.), Hakonarson, H. (Hakon), Ferrucci, L. (Luigi), Scott, R.A. (Robert), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Dedoussis, G.V. (George V.), Deloukas, P. (Panagiotis), Bertram, L. (Lars), Lindenberger, U. (Ulman), Berndt, S.I. (Sonja), Lindgren, C.M. (Cecilia), Timpson, N.J. (Nicholas), Tönjes, A. (Anke), Munroe, P. (Patricia), Sørensen, T.I.A. (Thorkild I.A.), Rotimi, C. (Charles), Arnett, D.K. (Donna), Oldehinkel, A.J. (Albertine), Kardia, S.L.R. (Sharon), Balkau, B. (Beverley), Gambaro, G. (Giovanni), Morris, A.P. (Andrew), Eriksson, J.G. (Johan G.), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Hunt, S.C. (Steven), Starr, J.M. (John), Deary, I.J. (Ian), Griffiths, L.R. (Lyn R.), Tiemeier, H.W. (Henning), Pirastu, N. (Nicola), Kaprio, J. (Jaakko), Wareham, N.J. (Nick), Perusse, L. (Louis), Wilson, J.G. (James), Girotto, S., Caulfield, M. (Mark), Raitakari, O.T. (Olli T.), Boomsma, D.I. (Dorret), Gieger, C. (Christian), van der Harst, P., Hicks, A.A. (Andrew), Kraft, P. (Peter), Sinisalo, J. (Juha), Knekt, P., Johannesson, M. (Magnus), Magnusson, P.K.E. (Patrik K. E.), Hamsten, A. (Anders), Borecki, I.B. (Ingrid), Vartiainen, E. (Erkki), Becker, D.M. (Diane), Bharadwaj, D. (Dwaipayan), Mohlke, K.L. (Karen), Boehnke, M. (Michael), Duijn, C.M. (Cornelia) van, Sanghera, D.K. (Dharambir), Teumer, A. (Alexander), Zeggini, E. (Eleftheria), Metspalu, A. (Andres), Gasparini, P. (Paolo), Ulivi, S. (Shelia), Ober, C. (Carole), Toniolo, D. (Daniela), Rudan, I. (Igor), Porteous, D.J. (David J.), Ciullo, M., Spector, T.D. (Timothy), Hayward, C. (Caroline), Dupuis, J. (Josée), Loos, R.J.F. (Ruth), Wright, A. (Alan), Chandak, G.R. (Giriraj), Vollenweider, P. (Peter), Shuldiner, A.R. (Alan), Ridker, P.M. (Paul), Rotter, J.I. (Jerome I.), Sattar, N. (Naveed), Gyllensten, U. (Ulf), North, K.E. (Kari), Pirastu, M. (Mario), Psaty, B.M. (Bruce), Weir, D.R. (David), Laakso, M. (Markku), Gudnason, V. (Vilmundur), Takahashi, A. (Atsushi), Chambers, J.C. (John C.), Kooner, J.S. (Jaspal S.), Strachan, D.P. (David P.), Campbell, H. (Harry), Hirschhorn, J.N. (Joel N.), Perola, M. (Markus), Polasek, O. (Ozren), Wilson, J.F. (James), Joshi, P.K. (Peter), Esko, T. (Tõnu), Mattsson, H. (Hannele), Eklund, N. (Niina), Gandin, I. (Ilaria), Nutile, T., Jackson, A.U. (Anne), Schurmann, C. (Claudia), Smith, A.V. (Davey), Zhang, W. (Weihua), Okada, Y. (Yukinori), Stancáková, A. (Alena), Faul, J.D. (Jessica D.), Zhao, W. (Wei), Bartz, T.M. (Traci M.), Concas, M.P. (Maria Pina), Franceschini, N. (Nora), Enroth, S. (Stefan), Vitart, V. (Veronique), Trompet, S. (Stella), Guo, X. (Xiuqing), Chasman, D.I. (Daniel), O'Connel, J.R. (Jeffrey R.), Corre, T. (Tanguy), Nongmaithem, S.S. (Suraj S.), Chen, Y. (Yuning), Mangino, M. (Massimo), Ruggiero, D., Traglia, M. (Michela), Farmaki, A.-E. (Aliki-Eleni), Kacprowski, T. (Tim), Bjonnes, A. (Andrew), Spek, A. (Ashley) van der, Wu, Y. (Ying), Giri, A.K. (Anil K.), Yanek, L.R. (Lisa), Wang, L. (Lihua), Hofer, E. (Edith), Rietveld, C.A. (Niels), McLeod, O. (Olga), Cornelis, M. (Marilyn), Pattaro, C. (Cristian), Verweij, N. (Niek), Baumbach, C. (Clemens), Abdellaoui, A. (Abdel), Warren, H. (Helen), Vuckovic, D. (Dragana), Mei, H. (Hao), Bouchard, C. (Claude), Perry, J.R.B. (John), Cappellani, S. (Stefania), Mirza, S.S. (Saira), Benton, M.C. (Miles C.), Broeckel, U. (Ulrich), Medland, S.E. (Sarah), Lind, P.A. (Penelope), Malerba, G. (Giovanni), Drong, A. (Alexander), Yengo, L. (Loic), Bielak, L.F. (Lawrence F.), Zhi, D. (Degui), Most, P.J. (Peter) van der, Shriner, D. (Daniel), Mägi, R. (Reedik), Hemani, G., Karaderi, T. (Tugce), Wang, Z. (Zhaoming), Liu, T. (Tian), Demuth, I. (Ilja), Zhao, J.H. (Jing Hua), Meng, W. (Weihua), Lataniotis, L. (Lazaros), Van Der Laan, S.W. (Sander W.), Bradfield, J.P. (Jonathan), Wood, A.R. (Andrew), Bonnefond, A. (Amélie), Ahluwalia, T.S. (Tarunveer Singh), Hall, L.M. (Leanne M.), Salvi, E. (Erika), Yazar, S. (Seyhan), Carstensen, L. (Lisbeth), Haan, H.G. (Hugoline) de, Abney, M. (Mark), Afzal, U. (Uzma), Allison, M.A. (Matthew), Amin, N. (Najaf), Asselbergs, F.W. (Folkert W.), Bakker, S.J.L. (Stephan), Barr, R.G. (Graham), Baumeister, S.E. (Sebastian), Benjamin, D.J. (Daniel J.), Bergmann, S. (Sven), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Campbell, A. (Archie), Chakravarti, A. (Aravinda), Chan, Y. (Yingleong), Chanock, S.J. (Stephen), Chen, C. (Constance), Chen, Y.-D.I. (Y.-D. Ida), Collins, F.S. (Francis), Connell, J. (John), Correa, A. (Adolfo), Cupples, L.A. (Adrienne), Davies, G. (Gail), Dörr, M. (Marcus), Ehret, G.B. (Georg), Ellis, S.B. (Stephen B.), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Ford, I., Fox, C.S. (Caroline), Frayling, T.M. (Timothy), Friedrich, N. (Nele), Geller, F. (Frank), Scotland, G. (Generation), Gillham-Nasenya, I. (Irina), Gottesman, R.F. (Rebecca), Graff, M.J. (Maud J.L.), Grodstein, F. (Francine), Gu, C. (Charles), Haley, C. (Chris), Hammond, C.J. (Christopher), Harris, S.E. (Sarah), Harris, T.B. (Tamara), Hastie, N. (Nick), Heard-Costa, N.L. (Nancy), Heikkilä, K. (Kauko), Hocking, L.J. (Lynne), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huffman, J.E. (Jennifer), Hysi, P.G. (Pirro), Ikram, M.A. (Arfan), Ingelsson, E. (Erik), Joensuu, A. (Anni), Johansson, A. (Åsa), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kähönen, M. (Mika), Kamatani, Y. (Yoichiro), Kanoni, S. (Stavroula), Kerr, S.M. (Shona), Khan, N.M. (Nazir M.), Koellinger, Ph.D. (Philipp), Koistinen, H.A. (Heikki A.), Kooner, M.K. (Manraj K.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lahti, J. (Jari), Launer, L.J. (Lenore), Lea, R.A. (Rodney A.), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David), Lind, L. (Lars), Loh, M. (Marie), Lokki, M.L., London, S.J. (Stephanie J.), Loomis, S.J. (Stephanie J.), Loukola, A. (Anu), Lu, Y. (Yingchang), Lumley, T. (Thomas), Lundqvist, A. (Annamari), Männistö, S. (Satu), Marques-Vidal, P. (Pedro), Masciullo, C. (Corrado), Matchan, A. (Angela), Mathias, J. (Jasmine), Matsuda, K. (Koichi), Meigs, J.B. (James), Meisinger, C. (Christa), Meitinger, T. (Thomas), Menni, C. (Cristina), Mentch, F.D. (Frank), Mihailov, E. (Evelin), Milani, L. (Lili), Montasser, M.E. (May E.), Montgomery, G.W. (Grant), Morrison, A.C. (Alanna), Myers, R.H. (Richard), Nadukuru, R. (Rajiv), Navarro, P. (Pau), Nalis, M. (Mari), Nieminen, M.S. (Markku S.), Nolte, I.M. (Ilja M.), O'Connor, G.T. (George), Ogunniyi, A. (Adesola), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Pankow, J.S. (James), Patarcic, I. (Inga), Pavani, F. (Francesca), Peyser, P.A. (Patricia A.), Pietilainen, K.H. (Kirsi Hannele), Poulter, N.R. (Neil), Prokopenko, I. (Inga), Ralhan, S. (Sarju), Redmond, P. (Paul), Rich, S.S. (Stephen S.), Rissanen, H. (Harri), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rose, R.J. (Richard J.), Sala, C. (Cinzia), Salako, B. (Babatunde), Salomaa, V. (Veikko), Sarin, A.-P., Saxena, R. (Richa), Schmidt, R. (Reinhold), Scott, L.J. (Laura), Scott, W.R. (William R.), Sennblad, B. (Bengt), Seshadri, S. (Sudha), Sever, P. (Peter), Shrestha, S. (Smeeta), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Soranzo, N. (Nicole), Sotoodehnia, N. (Nona), Southam, L. (Lorraine), Stanton, A. (Alice), Stathopoulou, M.G. (Maria G), Strauch, K. (Konstantin), Strawbridge, R.J. (Rona), Suderman, M.J. (Matthew J.), Tandon, N. (Nikhil), Tang, S.-T. (Sian-Tsun), Taylor, K.D. (Kent D.), Tayo, B. (Bamidele), Töglhofer, A.M. (Anna Maria), Tomaszewski, M. (Maciej), Tsernikova, N. (Natalia), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vaidya, D. (Dhananjay), Hylckama Vlieg, A. (Astrid) van, Setten, J. (Jessica) van, Vasankari, T. (Tuula), Vedantam, S. (Sailaja), Vlachopoulou, E. (Efthymia), Vozzi, D. (Diego), Vuoksimaa, E. (Eero), Waldenberger, M. (Melanie), Ware, E.B. (Erin B.), Wentworth-Shields, W. (William), Whitfield, J. (John), Wild, S. (Sarah), Willemsen, G.A.H.M. (Gonneke), Yajnik, C.S. (Chittaranjan S.), Yao, J. (Jie), Zaza, G. (Gianluigi), Zhu, X. (Xiaofeng), Salem, R.M. (Rany), Melbye, M. (Mads), Bisgaard, H. (Hans), Samani, N.J. (Nilesh), Cusi, D. (Daniele), Mackey, D.A. (David A.), Cooper, R.S. (Richard S.), Froguel, P. (Philippe), Pasterkamp, G. (Gerard), Grant, S.F.A. (Struan F.A.), Hakonarson, H. (Hakon), Ferrucci, L. (Luigi), Scott, R.A. (Robert), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Dedoussis, G.V. (George V.), Deloukas, P. (Panagiotis), Bertram, L. (Lars), Lindenberger, U. (Ulman), Berndt, S.I. (Sonja), Lindgren, C.M. (Cecilia), Timpson, N.J. (Nicholas), Tönjes, A. (Anke), Munroe, P. (Patricia), Sørensen, T.I.A. (Thorkild I.A.), Rotimi, C. (Charles), Arnett, D.K. (Donna), Oldehinkel, A.J. (Albertine), Kardia, S.L.R. (Sharon), Balkau, B. (Beverley), Gambaro, G. (Giovanni), Morris, A.P. (Andrew), Eriksson, J.G. (Johan G.), Wright, M.J. (Margaret), Martin, N.G. (Nicholas), Hunt, S.C. (Steven), Starr, J.M. (John), Deary, I.J. (Ian), Griffiths, L.R. (Lyn R.), Tiemeier, H.W. (Henning), Pirastu, N. (Nicola), Kaprio, J. (Jaakko), Wareham, N.J. (Nick), Perusse, L. (Louis), Wilson, J.G. (James), Girotto, S., Caulfield, M. (Mark), Raitakari, O.T. (Olli T.), Boomsma, D.I. (Dorret), Gieger, C. (Christian), van der Harst, P., Hicks, A.A. (Andrew), Kraft, P. (Peter), Sinisalo, J. (Juha), Knekt, P., Johannesson, M. (Magnus), Magnusson, P.K.E. (Patrik K. E.), Hamsten, A. (Anders), Borecki, I.B. (Ingrid), Vartiainen, E. (Erkki), Becker, D.M. (Diane), Bharadwaj, D. (Dwaipayan), Mohlke, K.L. (Karen), Boehnke, M. (Michael), Duijn, C.M. (Cornelia) van, Sanghera, D.K. (Dharambir), Teumer, A. (Alexander), Zeggini, E. (Eleftheria), Metspalu, A. (Andres), Gasparini, P. (Paolo), Ulivi, S. (Shelia), Ober, C. (Carole), Toniolo, D. (Daniela), Rudan, I. (Igor), Porteous, D.J. (David J.), Ciullo, M., Spector, T.D. (Timothy), Hayward, C. (Caroline), Dupuis, J. (Josée), Loos, R.J.F. (Ruth), Wright, A. (Alan), Chandak, G.R. (Giriraj), Vollenweider, P. (Peter), Shuldiner, A.R. (Alan), Ridker, P.M. (Paul), Rotter, J.I. (Jerome I.), Sattar, N. (Naveed), Gyllensten, U. (Ulf), North, K.E. (Kari), Pirastu, M. (Mario), Psaty, B.M. (Bruce), Weir, D.R. (David), Laakso, M. (Markku), Gudnason, V. (Vilmundur), Takahashi, A. (Atsushi), Chambers, J.C. (John C.), Kooner, J.S. (Jaspal S.), Strachan, D.P. (David P.), Campbell, H. (Harry), Hirschhorn, J.N. (Joel N.), Perola, M. (Markus), Polasek, O. (Ozren), and Wilson, J.F. (James)
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10-300, 2.1 × 10-6, 2.5 × 10-10 and 1.8 × 10-10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been p
Published: 2015
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45. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

Author: Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), and Morris, A.P. (Andrew)
Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
Published: 2015
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46. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, Loos, RJF, Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, and Loos, RJF
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap
Published: 2015

47. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author: Wessel, J, Chu, AY, Willems, SM, Wang, S, Yaghootkar, H, Brody, JA, Dauriz, M, Hivert, MF, Raghavan, S, Lipovich, L, Hidalgo, B, Fox, K, Huffman, JE, An, P, Lu, YC, Rasmussen-Torvik, LJ, Grarup, N, Ehm, MG, Li, Li, Baldridge, AS, Stancakova, A, Abrol, R, Besse, CL, Boland, A, Bork-Jensen, J, Fornage, M, Freitag, DF, Garcia, ME, Guo, XQ, Hara, K, Isaacs, Aaron, Jakobsdottir, J, Lange, LA, Layton, JC, Li, M, Zhao, JH, Meidtner, K, Morrison, AC, Nalls, MA, Peters, Marjolein, Sabater-Lleal, M, Schurmann, C, Silveira, A, Smith, AV, Southam, L, Stoiber, MH, Strawbridge, RJ, Taylor, KD, Varga, TV, Allin, KH, Amin, Najaf, Aponte, JL, Aung, T, Barbieri, C, Bihlmeyer, NA, Boehnke, M, Bombieri, C, Bowden, DW, Burns, SM, Chen, YN, Chen, YD, Cheng, CY (Ching-Yu), Correa, A, Czajkowski, J, Dehghan, Abbas, Ehret, GB, Eiriksdottir, G, Escher, SA, Farmaki, AE, Franberg, M, Gambaro, G, Giulianini, F, Goddard, WA, Goel, A, Gottesman, O, Grove, ML, Gustafsson, S, Hai, Y, Hallmans, G, Heo, J, Hoffmann, P, Ikram, MK, Jensen, RA, Jorgensen, ME, Jorgensen, T, Karaleftheri, M, Khor, CC, Kirkpatrick, A, Kraja, AT, Kuusisto, J, Lange, Edmee, Lee, IT, Lee, WJ, Leong, A, Liao, JM, Liu, CY, Liu, YM, Lindgren, CM, Linneberg, A, Malerba, G, Mamakou, V, Marouli, E, Maruthur, NM, Matchan, A, McKean-Cowdin, R, McLeod, O, Metcalf, GA, Mohlke, KL, Muzny, DM, Ntalla, I, Palmer, ND, Pasko, D, Peter, A, Rayner, NW, Renstrom, F, Rice, K, Sala, CF, Sennblad, B, Serafetinidis, I, Smith, JA, Soranzo, N, Speliotes, EK, Stahl, EA, Stirrups, K, Tentolouris, N, Thanopoulou, A, Torres, M, Traglia, M, Tsafantakis, E, Javad, S, Yanek, LR, Zengini, E, Becker, DM, Bis, JC, Brown, JB, Cupples, LA, Hansen, T, Ingelsson, E, Karter, AJ, Lorenzo, C, Mathias, RA, Norris, JM, Peloso, GM, Sheu, WHH, Toniolo, D, Vaidya, D, Varma, R, Wagenknecht, LE, Boeing, H, Bottinger, EP, Dedoussis, G, Deloukas, P, Ferrannini, E, Franco Duran, OH, Franks, PW, Gibbs, RA, Gudnason, V, Hamsten, A, Harris, TB, Hattersley, AT, Hayward, C, Hofman, Bert, Jansson, JH, Langenberg, C, Launer, LJ (Lenore), Levy, D, Oostra, Ben, O'Donnell, CJ, O'Rahilly, S, Padmanabhan, S, Pankow, JS, Polasek, O, Province, MA, Rich, SS, Ridker, PM, Rudan, I, Schulze, MB, Smith, BH, Uitterlinden, André, Walker, M, Watkins, H, Wong, TY (Tien Yin), Zeggini, E, Laakso, M, Borecki, IB, Chasman, DI, Pedersen, O, Psaty, BM, Tai, ES, Duijn, Cornelia, Wareham, NJ, Waterworth, DM, Boerwinkle, E, Kao, WHL, Florez, JC, Loos, RJF, Wilson, JG, Frayling, TM, Siscovick, DS, Dupuis, J, Rotter, JI, Meigs, JB, Scott, RA, Goodarzi, MO, Sharp, SJ, Forouhi, NG, Kerrison, ND, Lucarelli, DM, Sims, M, Barroso, I, McCarthy, MI, Arriola, L, Balkau, B, Barricarte, A, Gonzalez, C, Grioni, S, Kaaks, R, Key, TJ, Navarro, C, Nilsson, PM, Overvad, K, Palli, D, Panico, S, Quiros, JR, Rolandsson, O, Sacerdote, C, Sanchez, MJ (Maria-Jose), Slimani, N, Tjonneland, A, Tumino, R, van der A, DL, van der Schouw, YT, Riboli, E, Wessel, J, Chu, AY, Willems, SM, Wang, S, Yaghootkar, H, Brody, JA, Dauriz, M, Hivert, MF, Raghavan, S, Lipovich, L, Hidalgo, B, Fox, K, Huffman, JE, An, P, Lu, YC, Rasmussen-Torvik, LJ, Grarup, N, Ehm, MG, Li, Li, Baldridge, AS, Stancakova, A, Abrol, R, Besse, CL, Boland, A, Bork-Jensen, J, Fornage, M, Freitag, DF, Garcia, ME, Guo, XQ, Hara, K, Isaacs, Aaron, Jakobsdottir, J, Lange, LA, Layton, JC, Li, M, Zhao, JH, Meidtner, K, Morrison, AC, Nalls, MA, Peters, Marjolein, Sabater-Lleal, M, Schurmann, C, Silveira, A, Smith, AV, Southam, L, Stoiber, MH, Strawbridge, RJ, Taylor, KD, Varga, TV, Allin, KH, Amin, Najaf, Aponte, JL, Aung, T, Barbieri, C, Bihlmeyer, NA, Boehnke, M, Bombieri, C, Bowden, DW, Burns, SM, Chen, YN, Chen, YD, Cheng, CY (Ching-Yu), Correa, A, Czajkowski, J, Dehghan, Abbas, Ehret, GB, Eiriksdottir, G, Escher, SA, Farmaki, AE, Franberg, M, Gambaro, G, Giulianini, F, Goddard, WA, Goel, A, Gottesman, O, Grove, ML, Gustafsson, S, Hai, Y, Hallmans, G, Heo, J, Hoffmann, P, Ikram, MK, Jensen, RA, Jorgensen, ME, Jorgensen, T, Karaleftheri, M, Khor, CC, Kirkpatrick, A, Kraja, AT, Kuusisto, J, Lange, Edmee, Lee, IT, Lee, WJ, Leong, A, Liao, JM, Liu, CY, Liu, YM, Lindgren, CM, Linneberg, A, Malerba, G, Mamakou, V, Marouli, E, Maruthur, NM, Matchan, A, McKean-Cowdin, R, McLeod, O, Metcalf, GA, Mohlke, KL, Muzny, DM, Ntalla, I, Palmer, ND, Pasko, D, Peter, A, Rayner, NW, Renstrom, F, Rice, K, Sala, CF, Sennblad, B, Serafetinidis, I, Smith, JA, Soranzo, N, Speliotes, EK, Stahl, EA, Stirrups, K, Tentolouris, N, Thanopoulou, A, Torres, M, Traglia, M, Tsafantakis, E, Javad, S, Yanek, LR, Zengini, E, Becker, DM, Bis, JC, Brown, JB, Cupples, LA, Hansen, T, Ingelsson, E, Karter, AJ, Lorenzo, C, Mathias, RA, Norris, JM, Peloso, GM, Sheu, WHH, Toniolo, D, Vaidya, D, Varma, R, Wagenknecht, LE, Boeing, H, Bottinger, EP, Dedoussis, G, Deloukas, P, Ferrannini, E, Franco Duran, OH, Franks, PW, Gibbs, RA, Gudnason, V, Hamsten, A, Harris, TB, Hattersley, AT, Hayward, C, Hofman, Bert, Jansson, JH, Langenberg, C, Launer, LJ (Lenore), Levy, D, Oostra, Ben, O'Donnell, CJ, O'Rahilly, S, Padmanabhan, S, Pankow, JS, Polasek, O, Province, MA, Rich, SS, Ridker, PM, Rudan, I, Schulze, MB, Smith, BH, Uitterlinden, André, Walker, M, Watkins, H, Wong, TY (Tien Yin), Zeggini, E, Laakso, M, Borecki, IB, Chasman, DI, Pedersen, O, Psaty, BM, Tai, ES, Duijn, Cornelia, Wareham, NJ, Waterworth, DM, Boerwinkle, E, Kao, WHL, Florez, JC, Loos, RJF, Wilson, JG, Frayling, TM, Siscovick, DS, Dupuis, J, Rotter, JI, Meigs, JB, Scott, RA, Goodarzi, MO, Sharp, SJ, Forouhi, NG, Kerrison, ND, Lucarelli, DM, Sims, M, Barroso, I, McCarthy, MI, Arriola, L, Balkau, B, Barricarte, A, Gonzalez, C, Grioni, S, Kaaks, R, Key, TJ, Navarro, C, Nilsson, PM, Overvad, K, Palli, D, Panico, S, Quiros, JR, Rolandsson, O, Sacerdote, C, Sanchez, MJ (Maria-Jose), Slimani, N, Tjonneland, A, Tumino, R, van der A, DL, van der Schouw, YT, and Riboli, E
Abstract: Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
Published: 2015

48. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AV, Zhang, WH, Okada, Y, Stancakova, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MP, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, XQ, Chasman, DI, O'Connel, JR, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Michela, T, Farmaki, AE, Kacprowski, T, Bjonnes, A, van der Spek, Ashley, Wu, Y, Giri, AK, Yanek, LR, Wang, LH, Hofer, E, Rietveld, CA, McLeod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, Saira, Benton, MC, Broeckel, U, Medland, SE, Lind, P, Malerba, G, Drong, A, Yengo, L, Bielak, LF, Zhi, DG, van der Most, PJ, Shriner, D, Magi, R, Hemani, G, Karaderi, T, Wang, ZM, Liu, T, Demuth, I, Zhao, JH, Meng, WH, Lataniotis, L, Laan, Sander, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, L, Salvi, E, Yazar, S, Carstensen, L, de Haan, HG, Abney, M, Afzal, U, Allison, MA, Amin, Najaf, Asselbergs, FW, Bakker, SJL, Barr, RG, Baumeister, SE, Benjamin, DJ, Bergmann, S, Boerwinkle, E, Bottinger, EP, Campbell, A (Archie), Chakravarti, A, Chan, YL, Chanock, SJ, Chen, C (Christopher Li Hsian), Chen, YDI, Collins, FS, Connell, J, Correa, A, Cupples, LA, Smith, GD, Davies, G, Dorr, M, Ehret, G, Ellis, SB, Feenstra, B, Feitosa, MF, Ford, I, Fox, CS, Frayling, TM, Friedrich, N, Geller, F, Scotland, G, Gillham-Nasenya, I, Gottesman, O, Graff, M, Grodstein, F, Gu, C, Haley, C, Hammond, CJ, Harris, SE, Harris, TB, Hastie, ND, Heard-Costa, NL, Heikkila, K, Hocking, LJ, Homuth, G, Hottenga, Jouke-Jan, Huang, JY, Huffman, JE, Hysi, Pirro G., Arfan Ikram, M., Ingelsson, E, Joensuu, A, Johansson, A, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, P, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, Lenore J., Lea, RA, Lehne, B, Lehtimaki, T, Liewald, DCM, Lind, L, Loh, M, Lokki, ML, London, SJ, Loomis, SJ, Loukola, A, Lu, YC, Lumley, T, Lundqvist, A, Mannisto, S, Marques-Vidal, P, Masciullo, C, Matchan, A, Mathias, RA, Matsuda, K, Meigs, JB, Meisinger, C, Meitinger, T, Menni, C, Mentch, FD, Mihailov, E, Milani, L, Montasser, ME, Montgomery, G, Morrison, A, Myers, RH, Nadukuru, R, Navarro, P, Nelis, M, Nieminen, MS, Nolte, Ilja M., O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, WR, Pankow, JS, Patarcic, I, Pavani, F, Peyser, PA, Pietilainen, K, Poulter, N, Prokopenko, I, Ralhan, S, Redmond, P, Rich, SS, Rissanen, H, Robino, A, Rose, LM, Rose, R, Sala, C, Salako, B, Salomaa, V, Sarin, AP, Saxena, R, Schmidt, Heléna, Scott, LJ, Scott, WR, Sennblad, B, Seshadri, S, Sever, P, Shrestha, S, Smith, BH, Smith, JA, Soranzo, N, Sotoodehnia, N, Southam, L, Stanton, AV, Stathopoulou, MG, Strauch, K, Strawbridge, RJ, Suderman, MJ, Tandon, N, Tang, ST, Taylor, KD, Tayo, BO, Toglhofer, AM, Tomaszewski, M, Tsernikova, N, Tuomilehto, J, Uitterlinden, André, Vaidya, D, Vlieg, AV, van Setten, J, Vasankari, T, Vedantam, S, Vlachopoulou, E, Vozzi, D, Vuoksimaa, E, Waldenberger, M, Ware, EB, Wentworth-Shields, W, Whitfield, JB, Wild, S, Willemsen, G, Yajnik, CS, Yao, J, Zaza, G, Zhu, XF, Salem, RM, Melbye, M, Bisgaard, H, Samani, NJ, Cusi, D, Mackey, DA, Cooper, RS, Froguel, P, Pasterkamp, G, Grant, SFA, Hakonarson, H, Ferrucci, L, Scott, RA, Morris, AD, Palmer, CNA, Dedoussis, G, Deloukas, P, Bertram, L, Lindenberger, U, Berndt, SI, Lindgren, CM, Timpson, NJ, Tonjes, A, Munroe, PB, Sorensen, TIA, Rotimi, CN, Arnett, DK, Oldehinkel, Albertine J., Kardia, SLR, Balkau, B, Gambaro, G, Morris, AP, Eriksson, JG, Wright, MJ, Martin, NG, Hunt, SC, Starr, JM, Deary, IJ, Griffiths, LR, Tiemeier, Henning, Pirastu, N, Kaprio, J, Wareham, NJ, Peerusse, L, Wilson, JG, Girotto, G, Caulfield, MJ, Raitakari, O, Boomsma, DI, Gieger, C, van der Harst, P, Hicks, AA, Kraft, P, Sinisalo, J, Knekt, P, Johannesson, M, Magnusson, PKE, Hamsten, A, Schmidt, R, Borecki, IB, Vartiainen, E, Becker, DM, Bharadwaj, D, Mohlke, KL, Boehnke, M, van Duijn, Cornelia M., Sanghera, DK, Teumer, A, Zeggini, E, Metspalu, A, Gasparini, P, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, DJ, Ciullo, M, Spector, Tim D., Hayward, C, Dupuis, J, Loos, RJF, Wright, AF, Chandak, GR, Vollenweider, P, Shuldiner, AR, Ridker, PM, Rotter, JI, Sattar, N, Gyllensten, U, North, KE, Pirastu, M, Psaty, Bruce M., Weir, DR, Laakso, M, Gudnason, V, Takahashi, A, Chambers, JC, Kooner, JS, Strachan, DP, Campbell, H, Hirschhorn, JN, Perola, M, Polasek, O, Wilson, JF, Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AV, Zhang, WH, Okada, Y, Stancakova, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MP, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, XQ, Chasman, DI, O'Connel, JR, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Michela, T, Farmaki, AE, Kacprowski, T, Bjonnes, A, van der Spek, Ashley, Wu, Y, Giri, AK, Yanek, LR, Wang, LH, Hofer, E, Rietveld, CA, McLeod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, Saira, Benton, MC, Broeckel, U, Medland, SE, Lind, P, Malerba, G, Drong, A, Yengo, L, Bielak, LF, Zhi, DG, van der Most, PJ, Shriner, D, Magi, R, Hemani, G, Karaderi, T, Wang, ZM, Liu, T, Demuth, I, Zhao, JH, Meng, WH, Lataniotis, L, Laan, Sander, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, L, Salvi, E, Yazar, S, Carstensen, L, de Haan, HG, Abney, M, Afzal, U, Allison, MA, Amin, Najaf, Asselbergs, FW, Bakker, SJL, Barr, RG, Baumeister, SE, Benjamin, DJ, Bergmann, S, Boerwinkle, E, Bottinger, EP, Campbell, A (Archie), Chakravarti, A, Chan, YL, Chanock, SJ, Chen, C (Christopher Li Hsian), Chen, YDI, Collins, FS, Connell, J, Correa, A, Cupples, LA, Smith, GD, Davies, G, Dorr, M, Ehret, G, Ellis, SB, Feenstra, B, Feitosa, MF, Ford, I, Fox, CS, Frayling, TM, Friedrich, N, Geller, F, Scotland, G, Gillham-Nasenya, I, Gottesman, O, Graff, M, Grodstein, F, Gu, C, Haley, C, Hammond, CJ, Harris, SE, Harris, TB, Hastie, ND, Heard-Costa, NL, Heikkila, K, Hocking, LJ, Homuth, G, Hottenga, Jouke-Jan, Huang, JY, Huffman, JE, Hysi, Pirro G., Arfan Ikram, M., Ingelsson, E, Joensuu, A, Johansson, A, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, P, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, Lenore J., Lea, RA, Lehne, B, Lehtimaki, T, Liewald, DCM, Lind, L, Loh, M, Lokki, ML, London, SJ, Loomis, SJ, Loukola, A, Lu, YC, Lumley, T, Lundqvist, A, Mannisto, S, Marques-Vidal, P, Masciullo, C, Matchan, A, Mathias, RA, Matsuda, K, Meigs, JB, Meisinger, C, Meitinger, T, Menni, C, Mentch, FD, Mihailov, E, Milani, L, Montasser, ME, Montgomery, G, Morrison, A, Myers, RH, Nadukuru, R, Navarro, P, Nelis, M, Nieminen, MS, Nolte, Ilja M., O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, WR, Pankow, JS, Patarcic, I, Pavani, F, Peyser, PA, Pietilainen, K, Poulter, N, Prokopenko, I, Ralhan, S, Redmond, P, Rich, SS, Rissanen, H, Robino, A, Rose, LM, Rose, R, Sala, C, Salako, B, Salomaa, V, Sarin, AP, Saxena, R, Schmidt, Heléna, Scott, LJ, Scott, WR, Sennblad, B, Seshadri, S, Sever, P, Shrestha, S, Smith, BH, Smith, JA, Soranzo, N, Sotoodehnia, N, Southam, L, Stanton, AV, Stathopoulou, MG, Strauch, K, Strawbridge, RJ, Suderman, MJ, Tandon, N, Tang, ST, Taylor, KD, Tayo, BO, Toglhofer, AM, Tomaszewski, M, Tsernikova, N, Tuomilehto, J, Uitterlinden, André, Vaidya, D, Vlieg, AV, van Setten, J, Vasankari, T, Vedantam, S, Vlachopoulou, E, Vozzi, D, Vuoksimaa, E, Waldenberger, M, Ware, EB, Wentworth-Shields, W, Whitfield, JB, Wild, S, Willemsen, G, Yajnik, CS, Yao, J, Zaza, G, Zhu, XF, Salem, RM, Melbye, M, Bisgaard, H, Samani, NJ, Cusi, D, Mackey, DA, Cooper, RS, Froguel, P, Pasterkamp, G, Grant, SFA, Hakonarson, H, Ferrucci, L, Scott, RA, Morris, AD, Palmer, CNA, Dedoussis, G, Deloukas, P, Bertram, L, Lindenberger, U, Berndt, SI, Lindgren, CM, Timpson, NJ, Tonjes, A, Munroe, PB, Sorensen, TIA, Rotimi, CN, Arnett, DK, Oldehinkel, Albertine J., Kardia, SLR, Balkau, B, Gambaro, G, Morris, AP, Eriksson, JG, Wright, MJ, Martin, NG, Hunt, SC, Starr, JM, Deary, IJ, Griffiths, LR, Tiemeier, Henning, Pirastu, N, Kaprio, J, Wareham, NJ, Peerusse, L, Wilson, JG, Girotto, G, Caulfield, MJ, Raitakari, O, Boomsma, DI, Gieger, C, van der Harst, P, Hicks, AA, Kraft, P, Sinisalo, J, Knekt, P, Johannesson, M, Magnusson, PKE, Hamsten, A, Schmidt, R, Borecki, IB, Vartiainen, E, Becker, DM, Bharadwaj, D, Mohlke, KL, Boehnke, M, van Duijn, Cornelia M., Sanghera, DK, Teumer, A, Zeggini, E, Metspalu, A, Gasparini, P, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, DJ, Ciullo, M, Spector, Tim D., Hayward, C, Dupuis, J, Loos, RJF, Wright, AF, Chandak, GR, Vollenweider, P, Shuldiner, AR, Ridker, PM, Rotter, JI, Sattar, N, Gyllensten, U, North, KE, Pirastu, M, Psaty, Bruce M., Weir, DR, Laakso, M, Gudnason, V, Takahashi, A, Chambers, JC, Kooner, JS, Strachan, DP, Campbell, H, Hirschhorn, JN, Perola, M, Polasek, O, and Wilson, JF
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders(1), and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness(2). However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power(3,4). Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 x 10(-300), 2.1 x 10(-6), 2.5 x 10(-10) and 1.8 x 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples(5,6), no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection(7), this study provides evidence that increased stature and cognitive function have been positively sele
Published: 2015

49. Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease

Author: Sabater-Lleal, M., Huang, J., Chasman, D., Naitza, S., Dehghan, A., Johnson, A.D., Teumer, A., Reiner, A.P., Folkersen, L., Basu, S., Rudnicka, A.R., Trompet, S., Malarstig, A., Baumert, J., Bis, J.C., Guo, X.Q., Hottenga, J.J., Shin, S.Y., Lopez, L.M., Lahti, J., Tanaka, T., Yanek, L.R., Oudot-Mellakh, T., Wilson, J.F., Navarro, P., Huffman, J.E., Zemunik, T., Redline, S., Mehra, R., Pulanic, D., Rudan, I., Wright, A.F., Kolcic, I., Polasek, O., Wild, S.H., Campbell, H., Curb, J.D., Wallace, R., Liu, S.M., Eaton, C.B., Becker, D.M., Becker, L.C., Bandinelli, S., Raikkonen, K., Widen, E., Palotie, A., Fornage, M., Green, D., Gross, M., Davies, G., Harris, S.E., Liewald, D.C., Starr, J.M., Williams, F.M.K., Grant, P.J., Spector, T.D., Strawbridge, R.J., Silveira, A., Sennblad, B., Rivadeneira, F., Uitterlinden, A.G., Franco, O.H., Hofman, A., Dongen, J. van, Willemsen, G., Boomsma, D.I., Yao, J., Jenny, N.S., Haritunians, T., McKnight, B., Lumley, T., Taylor, K.D., Rotter, J.I., Psaty, B.M., Peters, A., Gieger, C., Illig, T., Grotevendt, A., Homuth, G., Volzke, H., Kocher, T., Goel, A., Franzosi, M.G., Seedorf, U., Clarke, R., Steri, M., Tarasov, K.V., Sanna, S., Schlessinger, D., Stott, D.J., Sattar, N., Buckley, B.M., Rumley, A., Lowe, G.D., McArdle, W.L., Chen, M.H., Tofler, G.H., Song, J., Boerwinkle, E., Folsom, A.R., Rose, L.M., Franco-Cereceda, A., Teichert, M., Ikram, M.A., Mosley, T.H., Bevan, S., Dichgans, M., Rothwell, P.M., Sudlow, C.L.M., Hopewell, J.C., Chambers, J.C., Saleheen, D., Kooner, J.S., Danesh, J., Nelson, C.P., Erdmann, J., Reilly, M.P., Kathiresan, S., Schunkert, H., Morange, P.E., Ferrucci, L., Eriksson, J.G., Jacobs, D., Deary, I.J., Soranzo, N., Witteman, J.C.M., Geus, E.J.C. de, Tracy, R.P., Hayward, C., Koenig, W., Cucca, F., Jukema, J.W., Eriksson, P., Seshadri, S., Markus, H.S., Watkins, H., Samani, N.J., Wallaschofski, H., Smith, N.L., Tregouet, D., Ridker, P.M., Tang, W.H., Strachan, D.P., Hamsten, A., O'Donnell, C.J., VTE Consortium, STROKE Consortium, WTCCC2, CD4 Consortium, CARDIoGRAM Consortium, Epidemiology, Cell biology, Urology, Internal Medicine, Immunology, Radiology & Nuclear Medicine, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
Subjects: Male, Netherlands Twin Register (NTR), Pathology, Myocardial Infarction, Genome-wide association study, Coronary Artery Disease, Disease, VARIANTS, 030204 cardiovascular system & hematology, Fibrinogen, Genome, 0302 clinical medicine, Risk Factors, Genotype, ARTERY-DISEASE, GENE-EXPRESSION, Aged, 80 and over, Genetics, INDIVIDUAL PARTICIPANT METAANALYSIS, 0303 health sciences, Hispanic or Latino, Venous Thromboembolism, Middle Aged, 3. Good health, Stroke, Meta-analysis, Medical genetics, Female, HEALTH, Cardiology and Cardiovascular Medicine, medicine.drug, Adult, medicine.medical_specialty, cardiovascular diseases, fibrinogen, gene expression, genome-wide association study, Adolescent, Implementation Science [NCEBP 3], Black People, Polymorphism, Single Nucleotide, White People, Young Adult, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Physiology (medical), medicine, Humans, CORONARY-HEART-DISEASE, HEMOSTASIS, Genetic Predisposition to Disease, Aged, 030304 developmental biology, business.industry, Heritability, GENOTYPES, MYOCARDIAL-INFARCTION, Genetic Loci, RISK-FACTORS, business
Abstract: Background— Estimates of the heritability of plasma fibrinogen concentration, an established predictor of cardiovascular disease, range from 34% to 50%. Genetic variants so far identified by genome-wide association studies explain only a small proportion ( Methods and Results— We conducted a meta-analysis of 28 genome-wide association studies including >90 000 subjects of European ancestry, the first genome-wide association meta-analysis of fibrinogen levels in 7 studies in blacks totaling 8289 samples, and a genome-wide association study in Hispanics totaling 1366 samples. Evaluation for association of single-nucleotide polymorphisms with clinical outcomes included a total of 40 695 cases and 85 582 controls for coronary artery disease, 4752 cases and 24 030 controls for stroke, and 3208 cases and 46 167 controls for venous thromboembolism. Overall, we identified 24 genome-wide significant ( P −8 ) independent signals in 23 loci, including 15 novel associations, together accounting for 3.7% of plasma fibrinogen variation. Gene-set enrichment analysis highlighted key roles in fibrinogen regulation for the 3 structural fibrinogen genes and pathways related to inflammation, adipocytokines, and thyrotrophin-releasing hormone signaling. Whereas lead single-nucleotide polymorphisms in a few loci were significantly associated with coronary artery disease, the combined effect of all 24 fibrinogen-associated lead single-nucleotide polymorphisms was not significant for coronary artery disease, stroke, or venous thromboembolism. Conclusions— We identify 23 robustly associated fibrinogen loci, 15 of which are new. Clinical outcome analysis of these loci does not support a causal relationship between circulating levels of fibrinogen and coronary artery disease, stroke, or venous thromboembolism.
Published: 2013
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50. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis

Author: Swerdlow, D.I., Holmes, M.V., Kuchenbaecker, K.B., Engmann, J.E.L., Shah, T., Sofat, R., Guo, Y.R., Chung, C., Peasey, A., Ster, R.P., Mooijaart, S.P., Ireland, H.A., Leusink, M., Langenberg, C., Li, K., Palmen, J., Howard, P., Cooper, J.A., Drenos, F., Hardy, J., Nalls, M.A., Li, Y.R., Lowe, G., Stewart, M., Bielinski, S.J., Peto, J., Timpson, N.J., Gallacher, J., Dunlop, M., Houlston, R., Tomlinson, I., Tzoulaki, I., Luan, J., Boer, J.M.A., Forouhi, N.G., Onland-Moret, N.C., Schouw, Y.T. van der, Schnabel, R.B., Hubacek, J.A., Kubinova, R., Baceviciene, M., Tamosiunas, A., Pajak, A., Topor-Madry, R., Malyutina, S.A., Baldassarre, D., Sennblad, B., Tremoli, E., Faire, U. de, Ferrucci, L., Bandenelli, S., Tanaka, T., Meschia, J.F., Singleton, A., Navis, G., Leach, I.M., Bakker, S.J.L., Gansevoort, R.T., Ford, I., Epstein, S.E., Burnett, M.S., Devaney, J.M., Jukema, J.W., Westendorp, R.G.J., Borst, G.J. de, Graaf, Y. van der, Jong, P.A. de, Maitland-van der Zee, A.H., Klungel, O.H., Boer, A. de, Doevendans, P.A., Stephens, J.W., Eaton, C.B., Robinson, J.G., Manson, J.E., Fowkes, F.G.R., Frayling, T.M., Price, J.F., Whincup, P.H., Morris, R.W., Lawlor, D.A., Smith, G.D., Ben-Shlomo, Y., Redline, S., Lange, L.A., Kumari, M., Wareham, N.J., Verschuren, W.M.M., Benjamin, E.J., Whittaker, J.C., Hamsten, A., Dudbridge, F., Delaney, J.A.C., Wong, A., Kuh, D., Hardy, R., Castillo, B.A., Connolly, J.J., Harst, P. van der, Brunner, E.J., Marmot, M.G., Wassel, C.L., Humphries, S.E., Talmud, P.J., Kivimaki, M., Asselbergs, F.W., Voevoda, M., Bobak, M., Pikhart, H., Wilson, J.G., Hakonarson, H., Reiner, A.P., Keating, B.J., Sattar, N., Hingorani, A.D., Casas, J.P., and Interleukin-6 Receptor Mendelian R
Abstract: BACKGROUND: A high circulating concentration of interleukin 6 is associated with increased risk of coronary heart disease. Blockade of the interleukin-6 receptor (IL6R) with a monoclonal antibody (tocilizumab) licensed for treatment of rheumatoid arthritis reduces systemic and articular inflammation. However, whether IL6R blockade also reduces risk of coronary heart disease is unknown. METHODS: Applying the mendelian randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis. FINDINGS: In 40 studies including up to 133,449 individuals, an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9·45%, 95% CI 8·34-10·57) as well as reduced C-reactive protein (decrease per allele 8·35%, 95% CI 7·31-9·38) and fibrinogen concentrations (decrease per allele 0·85%, 95% CI 0·60-1·10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25,458 coronary heart disease cases and 100,740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0·95, 95% CI 0·93-0·97, p=1·53×10(-5)). INTERPRETATION: On the basis of genetic evidence in human beings, IL6R signalling seems to have a causal role in development of coronary heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses. FUNDING: UK Medical Research Council; British Heart Foundation; Rosetrees Trust; US National Heart, Lung, and Blood Institute; Du Pont Pharma; Chest, Heart and Stroke Scotland; Wellcome Trust; Coronary Thrombosis Trust; Northwick Park Institute for Medical Research; UCLH/UCL Comprehensive Medical Research Centre; US National Institute on Aging; Academy of Finland; Netherlands Organisation for Health Research and Development; SANCO; Dutch Ministry of Public Health, Welfare and Sports; World Cancer Research Fund; Agentschap NL; European Commission; Swedish Heart-Lung Foundation; Swedish Research Council; Strategic Cardiovascular Programme of the Karolinska Institutet; Stockholm County Council; US National Institute of Neurological Disorders and Stroke; MedStar Health Research Institute; GlaxoSmithKline; Dutch Kidney Foundation; US National Institutes of Health; Netherlands Interuniversity Cardiology Institute of the Netherlands; Diabetes UK; European Union Seventh Framework Programme; National Institute for Healthy Ageing; Cancer Research UK; MacArthur Foundation.
Published: 2012

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