17 results on '"van Heemst, D"'
Search Results
2. Skewed X-inactivation is common in the general female population
- Author
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Shvetsova, E, Sofronova, A, Monajemi, R, Gagalova, K, Draisma, HHM, White, SJ, Santen, GWE, Lopes, SMCDS, Heijmans, BT, Van Meurs, J, Jansen, R, Franke, L, Kielbasa, SM, Den Dunnen, JT, 't Hoen, PAC, Boomsma, DI, Pool, R, Van Dongen, J, Hottenga, JJ, Van Greevenbroek, MMJ, Da Stehouwer, C, Van der Kallen, CJH, Schalkwijk, CG, Wijmenga, C, Zhernakova, S, Tigchelaar, EF, Slagboom, PE, Beekman, M, Deelen, J, Van Heemst, D, Veldink, JH, Van den Berg, LH, Van Duijn, CM, Hofman, BA, Uitterlinden, AG, Jhamai, PM, Verbiest, M, Suchiman, HED, Verkerk, M, Van der Breggen, R, Van Rooij, J, Lakenberg, N, Mei, H, Bot, J, Zhernakova, DV, 't Hof, PV, Deelen, P, Nooren, I, Moed, M, Vermaat, M, Luijk, R, Bonder, MJ, Van Iterson, M, Van Dijk, F, Van Galen, M, Arindrarto, W, Swertz, MA, Van Zwet, EW, Isaacs, A, Francioli, LC, Menelaou, A, Pulit, SL, Palamara, PF, Elbers, CC, Neerincx, PB, Ye, K, Guryev, V, Kloosterman, WP, Abdellaoui, A, Van Leeuwen, EM, Van Oven, M, Li, M, Laros, JF, Karssen, LC, Kanterakis, A, Amin, N, Lameijer, EW, Kattenberg, M, Dijkstra, M, Byelas, H, Van Setten, J, Van Schaik, BD, Nijman, IJ, Renkens, I, Marschall, T, Schonhuth, A, Hehir-Kwa, JY, Handsaker, RE, Polak, P, Sohail, M, Vuzman, D, Hormozdiari, F, Van Enckevort, D, Koval, V, Moed, MH, Van der Velde, KJ, Rivadeneira, F, Estrada, K, Medina-Gomez, C, McCarroll, SA, De Craen, AJ, Suchiman, HE, Oostra, B, Willemsen, G, Platteel, M, Pitts, SJ, Potluri, S, Sundar, P, Cox, DR, Sunyaev, SR, Stoneking, M, De Knijff, P, Kayser, M, Li, Q, Li, Y, Du, Y, Chen, R, Cao, H, Li, N, Cao, S, Wang, J, Bovenberg, JA, Pe'er, I, Van Ommen, GJ, De Bakker, PI, Consortium, Bios, Consortium, Gonl, BIOS consortium, GoNL consortium, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology and Data Science, AII - Inflammatory diseases, APH - Methodology, Experimental Immunology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Personalized Medicine, Biological Psychology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Interne Geneeskunde, RS: CARIM - R3 - Vascular biology, MUMC+: MA Reumatologie (9), MUMC+: MA Nefrologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Hematologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Endocrinologie (9), MUMC+: HVC Pieken Maastricht Studie (9), RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, MUMC+: MA Interne Geneeskunde (3), RS: Carim - B01 Blood proteins & engineering, RS: FHML MaCSBio, RS: CARIM - R1 - Thrombosis and haemostasis, RS: CARIM - R1.01 - Blood proteins & engineering, Biochemie, Psychiatry, VU University medical center, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Internal Medicine, Epidemiology, Genetic Identification, and Clinical Genetics
- Subjects
Netherlands Twin Register (NTR) ,Male ,0301 basic medicine ,Receptors, Cytoplasmic and Nuclear/genetics ,CHROMOSOME-INACTIVATION ,BIOS consortium ,Receptors, Cytoplasmic and Nuclear ,Septins/genetics ,Population genetics ,GoNL consortium ,Population/genetics ,Negative selection ,0302 clinical medicine ,X Chromosome Inactivation ,Receptors ,Non-U.S. Gov't ,Genetics (clinical) ,Netherlands ,Genetics & Heredity ,Genetics ,education.field_of_study ,Membrane Glycoproteins ,Dosage compensation ,DMD LOCUS ,Research Support, Non-U.S. Gov't ,Receptors, Peptide/genetics ,Intracellular Signaling Peptides and Proteins ,Peptide/genetics ,Single Nucleotide ,CARRIERS ,TRANSLOCATION ,VARIABILITY ,Female ,Life Sciences & Biomedicine ,EXPRESSION ,Biochemistry & Molecular Biology ,Receptors, Peptide ,Population ,ADRENOLEUKODYSTROPHY ,Biology ,Research Support ,Polymorphism, Single Nucleotide ,Article ,X-inactivation ,DUCHENNE MUSCULAR-DYSTROPHY ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Journal Article ,Humans ,Polymorphism ,Allele ,education ,Skewed X-inactivation ,Gene ,0604 Genetics ,Calcium-Binding Proteins/genetics ,Science & Technology ,CONSEQUENCES ,Calcium-Binding Proteins ,Membrane Glycoproteins/genetics ,030104 developmental biology ,Cytoplasmic and Nuclear/genetics ,PATTERNS ,Intracellular Signaling Peptides and Proteins/genetics ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,Septins ,030217 neurology & neurosurgery - Abstract
X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants.
- Published
- 2019
3. Defining the role of common variation in the genomic and biological architecture of adult human height
- Author
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Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, 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, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Hirschhorn, J, Frayling, T, Medical Research Council (MRC), APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., Merlini, PA., Berzuini, C., Bernardinelli, L., Peyvandi, F., Tubaro, M., Celli, P., Ferrario, M., Fetiveau, R., Marziliano, N., Casari, G., Galli, M., Ribichini, F., Rossi, M., Bernardi, F., Zonzin, P., Piazza, A., Yee, J., Friedlander, Y., Marrugat, J., Lucas, G., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Mooser, V., Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Psychiatry, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Wood, Ar, Pers, Th, Chu, Ay, Buchkovich, Ml, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Locke, Ae, Randall, Jc, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Zhao, Jh, Ehret, Gb, Feitosa, Mf, Fraser, Rm, Justice, Ae, Kleber, Me, Lui, Jc, MATEO LEACH, I, MEDINA GOMEZ, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Strawbridge, Rj, Sung, Yj, VAN DER LAAN, Sw, VAN SETTEN, J, VAN VLIET OSTAPTCHOUK, Jv, Arnlöv, J, Arscott, Gm, Bennett, Aj, Bolton, Jl, Boyd, Ha, Buckley, Bm, Caspersen, Ih, CLAUDI BOEHM, S, Daw, Ew, DE JONG, Pa, Denny, Jc, DHONUKSHE RUTTEN, R, Garcia, Me, Grammer, Tb, DE GROOT, Lc, Groves, Cj, Hartman, Ca, HEARD COSTA, Nl, Henders, Ak, Hillege, Hl, Hlatky, Ma, HOUWING DUISTERMAAT, Jj, James, Al, Johansson, A, Kho, An, Magnusson, Pk, Mcardle, Wl, Mckenzie, Ca, Mclaren, Pj, Monda, Kl, Morken, Ma, MÜLLER NURASYID, M, Musk, Aw, Nolte, Im, Nöthen, Mm, Rayner, Nw, Robertson, Nr, Rose, Lm, Schumacher, Fr, Scott, Ra, Smit, Jh, Smith, Av, Stanton, Av, Stott, Dj, Stringham, Hm, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Tyrer, Jp, VAN DIJK, S, VAN SCHOOR, Nm, VAN DER VELDE, N, VAN HEEMST, D, VAN OORT, Fv, Vermeulen, Sh, Vonk, Jm, Waite, Ll, Wilkens, Lr, Wojczynski, Mk, Wright, Af, Bakker, Sj, Bergman, Rn, Boomsma, Di, Bornstein, Sr, Brown, Mj, Caulfield, Mj, Crawford, Dc, Cupples, La, DE FAIRE, U, DEN RUIJTER, Hm, Eriksson, Jg, Forouhi, Ng, Gansevoort, Rt, Gejman, Pv, Haas, Dw, Harris, Tb, Hattersley, At, Heath, Ac, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hovingh, Gk, Humphries, Se, Hunt, Sc, Jacobs, Kb, Jarvelin, Mr, Jula, Am, Kastelein, Jj, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Kraja, At, Lakka, Ta, LE MARCHAND, L, Madden, Pa, Manunta, Paolo, Matise, Tc, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pramstaller, Pp, Price, Jf, Raitakari, Ot, Rao, Dc, Rice, Tk, Samani, Nj, Sarzynski, Ma, Schwarz, Pe, Shuldiner, Ar, Stolk, Rp, Tardif, Jc, Vohl, Mc, ELECTRONIC MEDICAL RECORDS AND GENOMICS, Consortium, Migen, Consortium, Page, Consortium, LIFELINES COHORT, Study, Asselbergs, Fw, Assimes, Tl, Boehm, Bo, Bottinger, Ep, Chambers, Jc, Chanock, Sj, DE BAKKER, Pi, Franks, Pw, Groop, Lc, Haiman, Ca, Hayes, Mg, Hunter, Dj, Jukema, Jw, Kaplan, Rc, Martin, Ng, Munroe, Pb, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Powell, Je, Ridker, Pm, Rotter, Ji, Saaristo, Te, Slagboom, Pe, Spector, Td, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, North, Ke, Strachan, Dp, Berndt, Si, Borecki, Ib, Mccarthy, Mi, Uitterlinden, Ag, VAN DUIJN, Cm, Willer, Cj, Price, Al, Loos, Rj, Weedon, Mn, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., Medina-Gomez C., Nalls M.A., Nyholt D.R., Palmer C.D., Pasko D., Pechlivanis S., Prokopenko I., Ried J.S., Ripke S., Shungin D., Stancakova A., Strawbridge R.J., Sung Y.J., Tanaka T., Teumer A., Trompet S., Van Der Laan S.W., Van Setten J., Van Vliet-Ostaptchouk J.V., Wang Z., Yengo L., Zhang W., Afzal U., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., Caspersen I.H., Chines P.S., Clarke R., Claudi-Boehm S., Cooper M., Daw E.W., De Jong P.A., Deelen J., Delgado G., Denny J.C., Dhonukshe-Rutten R., Dimitriou M., Doney A.S.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler J., Hall P., Haller T., Hallmans G., Hannemann A., Hartman C.A., Hassinen M., Hayward C., Heard-Costa N.L., Helmer Q., Hemani G., Henders A.K., Hillege H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.
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Netherlands Twin Register (NTR) ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,Electronic Medical Records and Genomics (eMEMERGEGE) Consortium ,Medizin ,Genome-wide association study ,Adult ,Analysis of Variance ,Body Height/genetics ,European Continental Ancestry Group/genetics ,Genetic Variation/genetics ,Genetics, Population ,Genome-Wide Association Study/methods ,Humans ,Oligonucleotide Array Sequence Analysis ,Polymorphism, Single Nucleotide/genetics ,heritability ,0302 clinical medicine ,Genome-wide ,SNPS ,snps ,Genetics & Heredity ,ddc:616 ,Genetics ,Medical And Health Sciences ,0303 health sciences ,education.field_of_study ,variants ,GENETIC-VARIATION ,Biological Sciences ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,body height ,genetic-variation ,Life Sciences & Biomedicine ,Single Nucleotide/genetics ,Human ,European Continental Ancestry Group ,Population ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,NO ,complex traits ,03 medical and health sciences ,Genetic variation ,heritability, adult, height ,Polymorphism ,Human height ,PAGEGE Consortium ,education ,Gene ,VLAG ,030304 developmental biology ,Global Nutrition ,Wereldvoeding ,genome-wide association study ,Science & Technology ,Whites ,Oligonucleotide Array Sequence Analysi ,MUTATIONS ,COMPLEX TRAITS ,ta1184 ,Klinisk medicin ,population genetics ,Genetic Variation ,Heritability ,ta3121 ,mutations ,Genetic architecture ,Body Height ,genetic variation ,MIGen Consortium ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Clinical Medicine ,030217 neurology & neurosurgery ,height ,LifeLines Cohort Study ,Developmental Biology ,Genome-Wide Association Study - Abstract
Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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- 2014
4. A SNP panel for identification of DNA and RNA specimens
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Yousefi, Soheil, Abbassi-Daloii, Tooba, Kraaijenbrink, Thirsa, Vermaat, Martijn, Mei, Hailiang, van't Hof, Peter, van Iterson, Maarten, Zhernakova, Daria V., Claringbould, Annique, Franke, Lude, 't Hart, Leen M., Slieker, Roderick C., van der Heijden, Amber, de Knijff, Peter, 't Hoen, Peter A. C., Jansen, R., van Meurs, J., Heijmans, B.T., Boomsma, D.I., van Dongen, J., Hottenga, Jouke-Jan, Slagboom, P.E., Suchiman, H. Eka D., van Zwet, Erik W., 't Hoen, P., Pool, R., van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, C., Zhernakova, A., Tigchelaar, E.F., Beekman, M, Deelen, J, van Heemst, D., Veldink, J H., van den Berg, L.H., van Duijn, C.M., Hofman, B. A., Uitterlinden, A. G., Jhamai, P. Mila, Verbiest, M., Verkerk, M., van der Breggen, Ruud, van Rooij, J., Lakenberg, N., Mei, H., Bot, J., Zhernakova, D. V., Van't Hof, P., Deelen, P., Nooren, I., Moed, M., Vermaat, M., Bonder, M.J., van Dijk, F., van Galen, M., Arindrarto, Wibowo, Kielbasa, Szymon M., Swertz, Morris A., Isaacs, A., Franke, L., Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology and Data Science, APH - Aging & Later Life, General practice, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome, Interne Geneeskunde, MUMC+: HVC Pieken Maastricht Studie (9), and MUMC+: MA Interne Geneeskunde (3)
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0301 basic medicine ,Netherlands Twin Register (NTR) ,BLOOD ,INDIVIDUAL IDENTIFICATION ,Individuality ,Linkage Disequilibrium ,0302 clinical medicine ,Gene Frequency ,MARKERS ,Genotype ,Ethnicity ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Mix up samples ,Genetics ,education.field_of_study ,CODIS CORE LOCI ,High-Throughput Nucleotide Sequencing ,16. Peace & justice ,Justice and Strong Institutions ,DNA profiling ,POPULATIONS ,DNA microarray ,MESSENGER-RNA ,Biotechnology ,Research Article ,Biobanking ,Patient Identification Systems ,SDG 16 - Peace ,lcsh:QH426-470 ,lcsh:Biotechnology ,Population ,UNITED-STATES ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,VALIDATION ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,lcsh:TP248.13-248.65 ,Journal Article ,SNP ,Humans ,030216 legal & forensic medicine ,Genetic Testing ,Genetic variation ,education ,Genotyping ,Forensics ,SDG 16 - Peace, Justice and Strong Institutions ,DNA ,DNA Fingerprinting ,Minor allele frequency ,FORENSIC IDENTIFICATION ,lcsh:Genetics ,030104 developmental biology ,Genetics, Population ,RNA ,MULTIPLEX ,Sample tracking ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] - Abstract
Background SNP panels that uniquely identify an individual are useful for genetic and forensic research. Previously recommended SNP panels are based on DNA profiles and mostly contain intragenic SNPs. With the increasing interest in RNA expression profiles, we aimed for establishing a SNP panel for both DNA and RNA-based genotyping. Results To determine a small set of SNPs with maximally discriminative power, genotype calls were obtained from DNA and blood-derived RNA sequencing data belonging to healthy, geographically dispersed, Dutch individuals. SNPs were selected based on different criteria like genotype call rate, minor allele frequency, Hardy–Weinberg equilibrium and linkage disequilibrium. A panel of 50 SNPs was sufficient to identify an individual uniquely: the probability of identity was 6.9 × 10− 20 when assuming no family relations and 1.2 × 10− 10 when accounting for the presence of full sibs. The ability of the SNP panel to uniquely identify individuals on DNA and RNA level was validated in an independent population dataset. The panel is applicable to individuals from European descent, with slightly lower power in non-Europeans. Whereas most of the genes containing the 50 SNPs are expressed in various tissues, our SNP panel needs optimization for other tissues than blood. Conclusions This first DNA/RNA SNP panel will be useful to identify sample mix-ups in biomedical research and for assigning DNA and RNA stains in crime scenes to unique individuals. Electronic supplementary material The online version of this article (10.1186/s12864-018-4482-7) contains supplementary material, which is available to authorized users.
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- 2018
5. Effect of intranasally administered insulin on cerebral blood flow and perfusion; a randomized experiment in young and older adults
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Rudi G. J. Westendorp, van Opstal Am, Iris Postmus, van der Grond J, van Heemst D, and Abimbola A. Akintola
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Adult ,Male ,continuous arterial spin labelling (CASL) ,magnetic resonance imaging (MRI) ,medicine.medical_treatment ,intranasal insulin ,Thalamus ,cerebral blood flow ,030209 endocrinology & metabolism ,Placebo ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,phase contrast MR angiography ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Administration, Intranasal ,Aged ,business.industry ,aging ,Age Factors ,Brain ,Cell Biology ,Middle Aged ,Crossover study ,Peripheral ,Cerebral blood flow ,Anesthesia ,Cerebrovascular Circulation ,Nasal administration ,Female ,business ,Perfusion ,030217 neurology & neurosurgery ,Magnetic Resonance Angiography ,Research Paper - Abstract
Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin (40IU) on cerebral blood flow (CBF) and perfusion in older (60-69 years, n=11) and younger (20-26 years, n=8) adults. Changes in CBF through the major cerebropetal arteries were assessed via phase contrast MR-angiography, and regional cortical tissue perfusion via pseudo-continuous arterial spin labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68.28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults. Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin (40IU) on cerebral blood flow (CBF) and perfusion in older (60-69 years, n=11) and younger (20-26 years, n=8) adults. Changes in CBF through the major cerebropetal arteries were assessed via phase contrast MR-angiography, and regional cortical tissue perfusion via pseudo-continuous arterial spin labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68.28±6.75 mL/100g/min versus 63.31±6.84 mL/100g/min, P=0.003). Thus, intranasal insulin improved tissue perfusion of the occipital cortical brain region and the thalamus in older adults.
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- 2017
6. A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function
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McCarthy, M.I., Porcu, E., Medici, M., Pistis, G., Volpato, C.B., Wilson, S.G., Cappola, A.R., Bos, S.D., Deelen, J., den Heijer, M., Freathy, R.M., Lahti, J., Liu, C., Lopez, L.M., Nolte, I.M., O'Connell, J.R., Tanaka, T., Trompet, S., Arnold, A., Bandinelli, S., Beekman, M., Böhringer, S., Brown, S.J., Buckley, B.M., Camaschella, C., de Craen, A.J.M., Davies, G., de Visser, M.C.H., Ford, I., Forsen, T., Frayling, T.M., Fugazzola, L., Gögele, M., Hattersley, A.T., Hermus, A.R., Hofman, A., Houwing-Duistermaat, J.J., Jensen, R.A., Kajantie, E., Kloppenburg, M., Lim, E.M., Masciullo, C., Mariotti, S., Minelli, C., Mitchell, B.D., Nagaraja, R., Netea-Maier, R.T., Palotie, A., Persani, L., Piras, M.G., Psaty, B.M., Räikkönen, K., Richards, J.B., Rivadeneira, F., Sala, C., Sabra, M.M., Sattar, N., Shields, B.M., Soranzo, N., Starr, J.M., Stott, D.J., Sweep, F.C.G.J., Usala, G., van der Klauw, M.M., van Heemst, D., van Mullem, A., H.Vermeulen, S., Visser, W.E., Walsh, J.P., Westendorp, R.G.J., Widen, E., Zhai, G., Cucca, F., Deary, I.J., Eriksson, J.G., Ferrucci, L., Fox, C.S., Jukema, J.W., Kiemeney, L.A., Pramstaller, P.P., Schlessinger, D., Shuldiner, A.R., Slagboom, E.P., Uitterlinden, A.G., Vaidya, B., Visser, T.J., Wolffenbuttel, B.H.R., Meulenbelt, I., Rotter, J.I., Spector, T.D., Hicks, A.A., Toniolo, D., Sanna, S., Peeters, R.P., Naitza, S., Internal Medicine, Clinical Genetics, Public Health, Epidemiology, Internal medicine, ICaR - Circulation and metabolism, Behavioural Sciences, Clinicum, Department of General Practice and Primary Health Care, Children's Hospital, Lastentautien yksikkö, Institute for Molecular Medicine Finland, Haartman Institute (-2014), Department of Medical and Clinical Genetics, Diabetes and Obesity Research Program, Developmental Psychology Research Group, Genomics of Neurological and Neuropsychiatric Disorders, Genomic Discoveries and Clinical Translation, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Porcu, E, Medici, M, Pistis, G, Volpato, Cb, Wilson, Sg, Cappola, Ar, Bos, Sd, Deelen, J, DEN HEIJER, M, Freathy, Rm, Lahti, J, Liu, C, Lopez, Lm, Nolte, Im, O'Connell, Jr, Tanaka, T, Trompet, S, Arnold, A, Bandinelli, S, Beekman, M, Böhringer, S, Brown, Sj, Buckley, Bm, Camaschella, Clara, DE CRAEN, Aj, Davies, G, DE VISSER, Mc, Ford, I, Forsen, T, Frayling, Tm, Fugazzola, L, Gögele, M, Hattersley, At, Hermus, Ar, Hofman, A, HOUWING DUISTERMAAT, Jj, Jensen, Ra, Kajantie, E, Kloppenburg, M, Lim, Em, Masciullo, C, Mariotti, S, Minelli, C, Mitchell, Bd, Nagaraja, R, NETEA MAIER, Rt, Palotie, A, Persani, L, Piras, Mg, Psaty, Bm, Räikkönen, K, Richards, Jb, Rivadeneira, F, Sala, C, Sabra, Mm, Sattar, N, Shields, Bm, Soranzo, N, Starr, Jm, Stott, Dj, Sweep, Fc, Usala, G, VAN DER KLAUW, Mm, VAN HEEMST, D, VAN MULLEM, A, Vermeulen, Sh, Visser, We, Walsh, Jp, Westendorp, Rg, Widen, E, Zhai, G, Cucca, F, Deary, Ij, Eriksson, Jg, Ferrucci, L, Fox, C, Jukema, Jw, Kiemeney, La, Pramstaller, Pp, Schlessinger, D, Shuldiner, Ar, Slagboom, Ep, Uitterlinden, Ag, Vaidya, B, Visser, Tj, Wolffenbuttel, Bh, Meulenbelt, I, Rotter, Ji, Spector, Td, Hicks, Aa, Toniolo, D, Sanna, S, Peeters, Rp, and Naitza, S.
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Male ,Cancer Research ,endocrine system diseases ,Factor binding protein 5 ,Thyroid Gland ,FACTOR BINDING PROTEIN-5 ,Thyrotropin ,Genome-wide association study ,Expression ,Aetiology, screening and detection [ONCOL 5] ,Growth ,Hyperthyroidism ,CLEFT-PALATE ,Serum TSH ,0302 clinical medicine ,Euthyroid ,Genetics (clinical) ,0303 health sciences ,Sex Characteristics ,factor binding protein-S ,Thyroid ,3. Good health ,medicine.anatomical_structure ,Phenotype ,NFIA ,Cleft palate ,GROWTH ,Genome wide Association ,Female ,Thyroid function ,hormones, hormone substitutes, and hormone antagonists ,Research Article ,Signal Transduction ,EXPRESSION ,medicine.medical_specialty ,endocrine system ,lcsh:QH426-470 ,cleft-palate ,515 Psychology ,education ,030209 endocrinology & metabolism ,Biology ,Polymorphism, Single Nucleotide ,Molecular epidemiology [NCEBP 1] ,03 medical and health sciences ,Thyroid-stimulating hormone ,Hypothyroidism ,SERUM TSH ,Internal medicine ,medicine ,Genetics ,Humans ,Hormonal regulation Translational research [IGMD 6] ,GENOME-WIDE ASSOCIATION ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Health aging / healthy living Cardiovascular diseases [IGMD 5] ,030304 developmental biology ,Molecular epidemiology Aetiology, screening and detection [NCEBP 1] ,Polymorphism, Genetic ,THYROTROPIN ,HORMONE PATHWAY GENES ,Hormonal regulation [IGMD 6] ,R1 ,Thyroxine ,Common variation ,lcsh:Genetics ,Endocrinology ,HYPOTHYROIDISM ,Hormone pathway genes ,genome-wide association ,Hormonal regulation Aetiology, screening and detection [IGMD 6] ,3111 Biomedicine ,COMMON VARIATION ,Hormone ,FOXE1 ,Genome-Wide Association Study ,Developmental Biology - Abstract
Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism., Author Summary Levels of thyroid hormones are tightly regulated by TSH produced in the pituitary, and even mild alterations in their concentrations are strong indicators of thyroid pathologies, which are very common worldwide. To identify common genetic variants associated with the highly heritable markers of thyroid function, TSH and FT4, we conducted a meta-analysis of genome-wide association studies in 26,420 and 17,520 individuals, respectively, of European ancestry with normal thyroid function. Our analysis identified 26 independent genetic variants regulating these traits, several of which are new, and confirmed previously detected polymorphisms affecting TSH (within the PDE8B gene and near CAPZB, MAF/LOC440389, and NR3C2) and FT4 (within DIO1) levels. Gender-specific differences in the genetic effects of several variants for TSH and FT4 levels were identified at several loci, which offer clues to understand the known sexual dimorphism in thyroid function and pathology. Of particular clinical interest, we show that TSH-associated loci contribute not only to normal variation, but also to TSH values outside reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings add to the developing landscape of the regulation of thyroid homeostasis and the consequences of genetic variation for thyroid related diseases.
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- 2013
7. Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited
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Deelen J., Beekman M., Uh H. -W., Helmer Q., Kuningas M., Christiansen L., Kremer D., van der Breggen R., Suchiman H. E. D., Lakenberg N., van den Akker E. B., Passtoors W. M., Tiemeier H., van Heemst D., de Craen A. J., Rivadeneira F., de Geus E. J., Perola M., van der Ouderaa F. J., Gunn D. A., Boomsma D. I., Uitterlinden A. G., Christensen K., van Duijn C. M., Heijmans B. T., Houwing-Duistermaat J. J., Westendorp R. G. J., Slagboom P. E., Epidemiology, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Biological Psychology, EMGO+ - Mental Health, Deelen J., Beekman M., Uh H.-W., Helmer Q., Kuningas M., Christiansen L., Kremer D., van der Breggen R., Suchiman H.E.D., Lakenberg N., van den Akker E.B., Passtoors W.M., Tiemeier H., van Heemst D., de Craen A.J., Rivadeneira F., de Geus E.J., Perola M., van der Ouderaa F.J., Gunn D.A., Boomsma D.I., Uitterlinden A.G., Christensen K., van Duijn C.M., Heijmans B.T., Houwing-Duistermaat J.J., Westendorp R.G.J., and Slagboom P.E.
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Adult ,Male ,Netherlands Twin Register (NTR) ,Longevity ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Cohort Studies ,Apolipoproteins E ,Genetic ,SDG 3 - Good Health and Well-being ,Alzheimer Disease ,Humans ,Genetic Predisposition to Disease ,genetics ,Longitudinal Studies ,human ,Aged ,apolipoprotein E ,Aged, 80 and over ,genome-wide association study ,Genome, Human ,Forkhead Box Protein O3 ,aging ,Forkhead Transcription Factors ,Original Articles ,aging apolipoprotein E genetics genome-wide association study human longevity apolipoprotein-e genotype growth-factor-i human longevity leiden longevity familial longevity alzheimers-disease nonagenarian siblings exceptional longevity depressive disorder artery-disease ,Middle Aged ,humanities ,Genetic Loci ,Case-Control Studies ,Female ,Proto-Oncogene Proteins c-akt - Abstract
By studying the loci that contribute to human longevity, we aim to identify mechanisms that contribute to healthy aging. To identify such loci, we performed a genome-wide association study (GWAS) comparing 403 unrelated nonagenarians from long-living families included in the Leiden Longevity Study (LLS) and 1670 younger population controls. The strongest candidate SNPs from this GWAS have been analyzed in a meta-analysis of nonagenarian cases from the Rotterdam Study, Leiden 85-plus study, and Danish 1905 cohort. Only one of the 62 prioritized SNPs from the GWAS analysis (P
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- 2011
8. Variation in the human TP53 gene affects old age survival and cancer mortality
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van Heemst, D, Mooijaart, S P, Beekman, M, Schreuder, J, de, Craen AJ, Brandt, B W, Slagboom, P E, Westendorp, R G, group, Long Life study, and Preventive Dentistry
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Aging ,medicine.medical_specialty ,Arginine ,media_common.quotation_subject ,Longevity ,Biology ,Biochemistry ,Mice ,Endocrinology ,Atrophy ,Neoplasms ,Internal medicine ,Genotype ,Genetics ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Prospective cohort study ,Molecular Biology ,Aged ,media_common ,Aged, 80 and over ,Polymorphism, Genetic ,Cancer ,Cell Biology ,Genes, p53 ,medicine.disease ,Ageing ,Apoptosis - Abstract
Longevity may depend on a balance between tumor suppression and tissue renewal mechanisms [Campisi, J., 2003. Cancer and ageing: rival demons? Nat. Rev. Cancer 3 (5), 339-349]. Mice with constitutively activated p53 are almost cancer free but their life span is reduced and accompanied by early tissue atrophy [Tyner et al., 2002. p53 mutant mice that display early ageing-associated phenotypes. Nature 415 (6867) 45-53]. Replacement of arginine (Arg) by proline (Pro) at position 72 of human p53 decreases its apoptotic potential [Dumont et al., 2003. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 33 (3), 357-365] providing a tool to test for a similar trade-off in humans. Using a formal meta-analysis of the published literature we show that carriers of the TP53 codon 72 Pro/Pro genotype have an increased cancer risk compared to Arg/Arg carriers (p
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- 2005
9. Variation in the SHC1 gene and longevity in humans
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Mooijaart, S P, van Heemst, D, Schreuder, J, van Gerwen, S, Beekman, M, Brandt, B W, Slagboom, P Eline, Westendorp, R G, Group, 'Long Life' Study, and Preventive Dentistry
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Adult ,Male ,Aging ,Candidate gene ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,media_common.quotation_subject ,Longevity ,Physiology ,Biology ,Biochemistry ,Endocrinology ,Gene Frequency ,Polymorphism (computer science) ,Valine ,Genetics ,Humans ,Prospective Studies ,Mortality ,Molecular Biology ,Allele frequency ,media_common ,Adaptor Proteins, Signal Transducing ,Aged ,Netherlands ,Aged, 80 and over ,Polymorphism, Genetic ,Mortality rate ,Genetic Variation ,Cell Biology ,SHC1 ,Survival Analysis ,Adaptor Proteins, Vesicular Transport ,Shc Signaling Adaptor Proteins ,Cohort ,Female ,Follow-Up Studies - Abstract
Mice in which the p66 SHC specific region of the SHC gene is deleted live 30% longer without apparent disease. These mice have lower levels of oxidative stress and apoptosis, both of which have been linked to old age survival in man. This makes SHC1 an important candidate gene for longevity in humans. We found no variations in the p66 specific region of the SHC1 gene in 30 young and 30 extreme long-lived subjects. Thus in man, no common sequence variations occur in p66 specific region of the SHC1 gene. In two independent cohorts of respectively 730 and 563 subjects aged 85 and over, we tested the only known non-synonymous polymorphism, Met 410 Val, for association with longevity using a prospective follow-up design. In the first cohort, we found increasing valine allele frequency in three strata of increasing age at death (2.8–5.2%). Moreover, compared to Met/Met carriers, mortality rate was a factor of 0.71 (95% CI 0.45–1.13) reduced for Met/Val carriers in the combined cohorts, with similar risk estimates in both cohorts. Low valine allele frequency resulted, however, in low power to detect statistical significance. These data suggest that an association between the Met 410 Val polymorphism and longevity in humans may exist.
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- 2004
10. New genetic loci link adipose and insulin biology to body fat distribution
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Shungin, Dmitry, Winkler, Thomas W, Workalemahu, Tsegaselassie, Hartman, Catharina A, Duncan, Emma L, Ntzani, Evangelia E, Oei, Ling, Albagha, Omar M E, Amin, Najaf, Kemp, John P, Koller, Daniel L, Li, Guo, Liu, Ching-Ti, Minster, Ryan L, Hassinen, Maija, Moayyeri, Alireza, Vandenput, Liesbeth, Willner, Dana, Xiao, Su-Mei, Yerges-Armstrong, Laura M, Zheng, Hou-Feng, Alonso, Nerea, Eriksson, Joel, Kammerer, Candace M, Kaptoge, Stephen K, Hayward, Caroline, Leo, Paul J, Thorleifsson, Gudmar, Wilson, Scott G, Wilson, James F, Aalto, Ville, Alen, Markku, Aragaki, Aaron K, Aspelund, Thor, Center, Jacqueline R, Dailiana, Zoe, Heikkilä, Kauko, Duggan, David J, Garcia, Melissa, Garcia-Giralt, Natàlia, Giroux, Sylvie, Hallmans, Göran, Hocking, Lynne J, Husted, Lise Bjerre, Jameson, Karen A, Khusainova, Rita, Kim, Ghi Su, Herzig, Karl-Heinz, Kooperberg, Charles, Koromila, Theodora, Kruk, Marcin, Laaksonen, Marika, Lacroix, Andrea Z, Lee, Seung Hun, Leung, Ping C, Lewis, Joshua R, Masi, Laura, Mencej-Bedrac, Simona, Helmer, Quinta, Nguyen, Tuan V, Nogues, Xavier, Patel, Millan S, Prezelj, Janez, Rose, Lynda M, Scollen, Serena, Siggeirsdottir, Kristin, Smith, Albert V, Svensson, Olle, Trompet, Stella, Hillege, Hans L, Trummer, Olivia, van Schoor, Natasja M, Woo, Jean, Zhu, Kun, Balcells, Susana, Brandi, Maria Luisa, Buckley, Brendan M, Cheng, Sulin, Christiansen, Claus, Cooper, Cyrus, Holmen, Oddgeir, Dedoussis, George, Ford, Ian, Frost, Morten, Goltzman, David, González-Macías, Jesús, Kähönen, Mika, Karlsson, Magnus, Khusnutdinova, Elza, Koh, Jung-Min, Kollia, Panagoula, Hunt, Steven C, Langdahl, Bente Lomholt, Leslie, William D, Lips, Paul, Ljunggren, Östen, Lorenc, Roman S, Marc, Janja, Mellström, Dan, Obermayer-Pietsch, Barbara, Olmos, José M, Pettersson-Kymmer, Ulrika, Isaacs, Aaron, Reid, David M, Riancho, José A, Ridker, Paul M, Rousseau, François, Slagboom, P Eline, Tang, Nelson L S, Urreizti, Roser, Van Hul, Wim, Viikari, Jorma, Zarrabeitia, María T, Wu, Joseph M W, Ittermann, Till, Aulchenko, Yurii S, Castano-Betancourt, Martha, Grundberg, Elin, Herrera, Lizbeth, Ingvarsson, Thorvaldur, Johannsdottir, Hrefna, Kwan, Tony, Li, Rui, Luben, Robert, Medina-Gómez, Carolina, James, Alan L, Palsson, Stefan Th, Reppe, Sjur, Rotter, Jerome I, Sigurdsson, Gunnar, van Meurs, Joyce B J, Verlaan, Dominique, Williams, Frances M K, Wood, Andrew R, Zhou, Yanhua, Gautvik, Kaare M, Johansson, Ingegerd, Pastinen, Tomi, Raychaudhuri, Soumya, Cauley, Jane A, Chasman, Daniel I, Clark, Graeme R, Cummings, Steven R, Danoy, Patrick, Dennison, Elaine M, Eastell, Richard, Eisman, John A, Juliusdottir, Thorhildur, Gudnason, Vilmundur, Hofman, Albert, Jackson, Rebecca D, Jones, Graeme, Jukema, J Wouter, Khaw, Kay-Tee, Lehtimäki, Terho, Liu, Yongmei, Lorentzon, Mattias, McCloskey, Eugene, Kalafati, Ioanna-Panagiota, Mitchell, Braxton D, Nandakumar, Kannabiran, Nicholson, Geoffrey C, Oostra, Ben A, Peacock, Munro, Pols, Huibert A P, Prince, Richard L, Raitakari, Olli, Reid, Ian R, Robbins, John, Kinnunen, Leena, Sambrook, Philip N, Sham, Pak Chung, Shuldiner, Alan R, Tylavsky, Frances A, van Duijn, Cornelia M, Wareham, Nick J, Cupples, L Adrienne, Econs, Michael J, Evans, David M, Harris, Tamara B, Koenig, Wolfgang, Kung, Annie Wai Chee, Psaty, Bruce M, Reeve, Jonathan, Spector, Timothy D, Streeten, Elizabeth A, Zillikens, M Carola, Thorsteinsdottir, Unnur, Ohlsson, Claes, Karasik, David, Richards, J Brent, Kooner, Ishminder K, Brown, Matthew A, Stefansson, Kari, Uitterlinden, André G, Ralston, Stuart H, Ioannidis, John P A, Kiel, Douglas P, Rivadeneira, Fernando, Sandholm, Niina, Salem, Rany M, McKnight, Amy Jayne, Kratzer, Wolfgang, Brennan, Eoin P, Forsblom, Carol, Isakova, Tamara, McKay, Gareth J, Williams, Winfred W, Sadlier, Denise M, Mäkinen, Ville-Petteri, Swan, Elizabeth J, Palmer, Cameron, Boright, Andrew P, Lamina, Claudia, Ahlqvist, Emma, Deshmukh, Harshal A, Keller, Benjamin J, Huang, Huateng, Ahola, Aila, Fagerholm, Emma, Gordin, Daniel, Harjutsalo, Valma, He, Bing, Heikkilä, Outi, Buchkovich, Martin L, Leander, Karin, Hietala, Kustaa, Kytö, Janne, Lahermo, Päivi, Lehto, Markku, Österholm, Anne-May, Parkkonen, Maija, Pitkäniemi, Janne, Rosengård-Bärlund, Milla, Saraheimo, Markku, Sarti, Cinzia, Lee, Nanette R, Söderlund, Jenny, Soro-Paavonen, Aino, Syreeni, Anna, Thorn, Lena M, Tikkanen, Heikki, Tolonen, Nina, Tryggvason, Karl, Tuomilehto, Jaakko, Wadén, Johan, Gill, Geoffrey V, Lichtner, Peter, Prior, Sarah, Guiducci, Candace, Mirel, Daniel B, Taylor, Andrew, Hosseini, Mohsen, Parving, Hans-Henrik, Rossing, Peter, Tarnow, Lise, Ladenvall, Claes, Alhenc-Gelas, François, Lind, Lars, Lefebvre, Pierre, Rigalleau, Vincent, Roussel, Ronan, Tregouet, David-Alexandre, Maestroni, Anna, Maestroni, Silvia, Falhammar, Henrik, Gu, Tianwei, Möllsten, Anna, Cimponeriu, Dan, Lindström, Jaana, Mihai, Ioana, Mota, Maria, Mota, Eugen, Serafinceanu, Cristian, Stavarachi, Monica, Hanson, Robert L, Nelson, Robert G, Kretzler, Matthias, Colhoun, Helen M, Panduru, Nicolae Mircea, Lobbens, Stéphane, Gu, Harvest F, Brismar, Kerstin, Zerbini, Gianpaolo, Hadjadj, Samy, Marre, Michel, Groop, Leif, Lajer, Maria, Bull, Shelley B, Waggott, Daryl, Paterson, Andrew D, Savage, David A, Bain, Stephen C, Martin, Finian, Hirschhorn, Joel N, Godson, Catherine, Florez, Jose C, Groop, Per-Henrik, Maxwell, Alexander P, Willer, Cristen J, Schmidt, Ellen M, Mach, François, Sengupta, Sebanti, Peloso, Gina M, Gustafsson, Stefan, Kanoni, Stavroula, Ganna, Andrea, Chen, Jin, Mora, Samia, Beckmann, Jacques S, Bragg-Gresham, Jennifer L, Magnusson, Patrik Ke, Chang, Hsing-Yi, Demirkan, Ayşe, Den Hertog, Heleen M, Do, Ron, Donnelly, Louise A, Ehret, Georg B, Esko, Tõnu, Feitosa, Mary F, Ferreira, Teresa, Fischer, Krista, Mahajan, Anubha, Fontanillas, Pierre, Fraser, Ross M, Freitag, Daniel F, Gurdasani, Deepti, Hyppönen, Elina, Jackson, Anne U, Johansson, Åsa, Johnson, Toby, Heard-Costa, Nancy L, McArdle, Wendy L, Kaakinen, Marika, Kettunen, Johannes, Kleber, Marcus E, Li, Xiaohui, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K E, Mangino, Massimo, Mihailov, Evelin, Montasser, May E, Menni, Cristina, Müller-Nurasyid, Martina, Nolte, Ilja M, O'Connell, Jeffrey R, Palmer, Cameron D, Perola, Markus, Petersen, Ann-Kristin, Sanna, Serena, Saxena, Richa, Service, Susan K, Shah, Sonia, Merger, Sigrun, Sidore, Carlo, Song, Ci, Strawbridge, Rona J, Surakka, Ida, Tanaka, Toshiko, Teslovich, Tanya M, Van den Herik, Evita G, Voight, Benjamin F, Volcik, Kelly A, Waite, Lindsay L, Wong, Andrew, Wu, Ying, Zhang, Weihua, Absher, Devin, Asiki, Gershim, Barroso, Inês, Been, Latonya F, Bolton, Jennifer L, Milani, Lili, Bonnycastle, Lori L, Brambilla, Paolo, Burnett, Mary S, Cesana, Giancarlo, Dimitriou, Maria, Doney, Alex S F, Döring, Angela, Elliott, Paul, Epstein, Stephen E, Eyjolfsson, Gudmundur Ingi, Mills, Rebecca, Gigante, Bruna, Goodarzi, Mark O, Grallert, Harald, Gravito, Martha L, Groves, Christopher J, Hartikainen, Anna-Liisa, Hernandez, Dena, Hicks, Andrew A, Holm, Hilma, Hung, Yi-Jen, Illig, Thomas, Jones, Michelle R, Kaleebu, Pontiano, Kastelein, John J P, Kim, Eric, Klopp, Norman, Komulainen, Pirjo, Monda, Keri L, Kumari, Meena, Langenberg, Claudia, Lin, Shih-Yi, Loos, Ruth J F, Meisinger, Christa, Mooijaart, Simon P, Müller, Gabrielle, Nagaraja, Ramaiah, Narisu, Narisu, Nieminen, Tuomo V M, Nsubuga, Rebecca N, Olafsson, Isleifur, Ong, Ken K, Palotie, Aarno, Papamarkou, Theodore, Pomilla, Cristina, Mühleisen, Thomas W, Pouta, Anneli, Rader, Daniel J, Reilly, Muredach P, Rudan, Igor, Ruokonen, Aimo, Samani, Nilesh, Scharnagl, Hubert, Seeley, Janet, Roman, Tamara S, Mulas, Antonella, Silander, Kaisa, Stančáková, Alena, Stirrups, Kathleen, Swift, Amy J, Tiret, Laurence, Uitterlinden, Andre G, van Pelt, L Joost, Vedantam, Sailaja, Wainwright, Nicholas, Wijmenga, Cisca, Müller, Gabriele, Wild, Sarah H, Willemsen, Gonneke, Wilsgaard, Tom, Young, Elizabeth H, Zhao, Jing Hua, Adair, Linda S, 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NourEddine, Van Vliet-Ostaptchouk, Jana V, Hager, Jörg, Hunt, Sarah E, Kang, Hyun M, Kessler, Thorsten, Knowles, Joshua W, Kolovou, Genovefa, Langford, Cordelia, Lokki, Marja-Liisa, Lundmark, Anders, Maouche, Seraya, Nikus, Kjell, Rayner, N William, Rosinger, Silke, Rubin, Diana, Rumpf, Moritz P, Schäfer, Arne, Sivananthan, Mohan, Stewart, Alexandre F R, Tan, Sian-Tsung, Thorgeirsson, Gudmundur, van der Schoot, C Ellen, Wagner, Peter J, Wells, George A, Wild, Philipp S, Ärnlöv, Johan, Basart, Hanneke, Cambien, Francois, Cupples, Adrienne L, Arscott, Gillian M, Diemert, Patrick, Evans, Alun, Ferrario, Marco M, Gauguier, Dominique, Go, Alan S, Goodall, Alison H, Gudnason, Villi, Hazen, Stanley L, Jang, Yangsoo, Kim, Hyo-Soo, Laaksonen, Reijo, Lee, Ji-Young, Ouwehand, Willem H, Parish, Sarah, Park, Jeong E, Bellis, Claire, Schadt, Eric, Shah, Svati H, Stark, Klaus, Trégouët, David-Alexandre, Virtamo, Jarmo, Bennett, Amanda J, Wareham, Nicholas, Zimmermann, Martina E, Nieminen, Markku S, Hengstenberg, Christian, Berne, Christian, Zalloua, Pierre A, Blankenberg, Stefan S, Pers, Tune H, Blüher, Matthias, O'Donnell, Christopher, Roberts, Robert, Schunkert, Heribert, Garnaas, Maija, Böger, Carsten A, Bonnet, Fabrice, Tin, Adrienne, Taliun, Daniel, Li, Man, Gao, Xiaoyi, Gorski, Mathias, Yang, Qiong, Hundertmark, Claudia, Böttcher, Yvonne, Foster, Meredith C, O'Seaghdha, Conall M, Struchalin, Maksim, Gierman, Hinco J, Feitosa, Mary, Atkinson, Elizabeth J, Carba, Delia B, Chouraki, Vincent, Holliday, Elizabeth G, Sorice, Rossella, Kutalik, Zoltan, Deshmukh, Harshal, Chu, Audrey Y, Murgia, Federico, Caspersen, Ida H, Imboden, Medea, Kollerits, Barbara, Schmidt, Helena, Cavalieri, Margherita, Rao, Madhumathi, de Andrade, Mariza, Turner, Stephen T, Ding, Jingzhong, Daw, E Warwick, Freedman, Barry I, Wichmann, H -Erich, Minelli, Cosetta, Wheeler, Heather E, Deelen, Joris, Zaboli, Ghazal, Ellinghaus, David, Nöthlings, Ute, Jacobs, Gunnar, Biffar, Reiner, Endlich, Karlhans, Nauck, 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Surdulescu, G., Travers, ME., Tsaprouni, L., Tsoka, S., Wilk, A., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., Heiss, G., Taylor, K., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Crawford, D., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Ritchie, M., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Peters, U., Anderson, G., Carlson, C., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Stolk, L., He, C., Sulem, P., Barbalic, M., Broer, L., Byrne, EM., Gudbjartsson, DF., McArdle, PF., Porcu, E., van Wingerden, S., Zhuang, W., Albrecht, E., Alizadeh, BZ., Lauc, LB., Broekmans, FJ., Burri, A., Chanock, SJ., Chen, C., Corre, T., Coviello, AD., d'Adamo, P., Davies, G., Deary, IJ., Ebrahim, S., Fauser, BC., Ferreli, L., Folsom, AR., Garcia, ME., Hall, P., Haller, T., Hankinson, SE., Hass, M., Heath, AC., Janssens, AC., Keyzer, J., Lahti, J., Lai, S., Laisk, T., Laven, JS., Liu, J., Lopez, LM., Louwers, YV., Marongiu, M., Klaric, IM., Masciullo, C., McKnight, B., Medland, SE., Melzer, D., Newman, AB., Paré, G., Peeters, PH., Plump, AS., Pop, VJ., Räikkönen, K., Salumets, A., Smith, JA., Stacey, SN., Starr, JM., Stathopoulou, MG., Tenesa, A., Thorand, B., Tryggvadottir, L., Tsui, K., van Dam RM., van Gils CH., van Nierop, P., Vink, JM., Voorhuis, M., Wallaschofski, H., Widen, E., Wijnands-van Gent CJ., Zgaga, L., Zygmunt, M., Arnold, AM., Buring, JE., Crisponi, L., Demerath, EW., Hunter, DJ., Schlessinger, D., Murray, A., Murabito, JM., Visser, JA., Lunetta, KL., Elks, CE., Cousminer, DL., Feenstra, B., Lin, P., van Wingerden SW., Smith, EN., Warrington, NM., Alavere, H., Barroso, I., Berenson, GS., Blackburn, H., Busonero, F., Chen, W., Couper, D., Easton, DF., Foroud, T., Geller, F., Hernandez, DG., Kilpeläinen, TO., Li, S., Melbye, M., Murray, JC., Murray, SS., Nelis, M., Ness, AR., Northstone, K., Pennell, CE., Pharoah, P., Rafnar, T., Rice, JP., Ring, SM., Schork, NJ., Segrè, AV., Sovio, U., Srinivasan, SR., Tammesoo, ML., Tyrer, J., Weedon, MN., Wichmann, H., Young, L., Zhuang, WV., Bierut, LJ., Boyd, HA., Department of Clinical Sciences, Lund University [Lund], Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Department of Odontology, Umeå University, Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Laboratory of Image Science and Technology [Nanjing] (LIST), Southeast University [Jiangsu]-School of Computer Science and Engineering, Limnology, Ecology, Estonian Genome and Medicine, University of Tartu, Institute of Molecular and Cell Biology, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Institute of Medical Informatics, Biometry and Epidemiology, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Genetic Epidemiology Unit, 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(INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Department of Pharmacy Sciences, Creighton University Medical Center, Medical Department III, Universität Leipzig, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Public Health and Clinical Medicine, Medstar Research Institute, Genetics and Pathology, Finnish Institute of Occupational Health, Epidemiology, University Medical Centre Groningen, Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California [Irvine] (UC Irvine), Department of Odontology, Cariology, Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Division of Cardiology, Geneva University Hospital (HUG), Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Anaesthesia and Intensive care, Royal Aberdeen Childrens Hospital, UCL Institute of neurology, UCL Institute of Neurology, Human Genetics, The Wellcome Trust Sanger Institute [Cambridge], 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= University of Helsinki, Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, Department of Pediatrics, Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Department of Public Health, South Ostrobothnia Central Hospital, Department of Clinical and Preventive Medicine, Danube-University Krems, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), Institute of Public Health and Clinical Nutrition, University of Eastern Finland, MRC epidemiology Unit, Institute of Epidemiology, Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Oncology, Queensland Brain Institute, University of Queensland [Brisbane], Harvard Reproductive Sciences Center and Reproductive Endocrine Unit, 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(BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Endocrinology and Metabolism, The Churchill Hospital-Oxford Centre for Diabetes, Landsteiner Laboratory, Clinical Haematology, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Lund University Diabetes Centre-Lund University [Lund], Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Technical University of Denmark [Lyngby] (DTU), Université de Lausanne (UNIL), Universität Duisburg-Essen [Essen], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), University of California [Berkeley], University of California-University of California, Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche 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Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Helmholtz-Zentrum München (HZM), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Internal Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Medical Informatics, Obstetrics & Gynecology, Lund University [Lund]-Lund University Diabetes Centre, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institute of Medicine-University of Gothenburg (GU), Signalisation et Transports Ioniques Membranaires ( STIM ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Technical University of Denmark [Lyngby] ( DTU ), Laboratory of Image Science and Technology [Nanjing] ( LIST ), Department of Medical Epidemiology and Biostatistics ( MEB ), University of Lausanne, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Erasmus MC, Space Sciences Laboratory [Berkeley] ( SSL ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Université de Lille-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of Leipzig, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institute of Epidemiology [Neuherberg] ( EPI ), University of California [Irvine] ( UCI ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Geneva University Hospital ( HUG ), Bonn Universität [Bonn], Indian Institute of Technology Kanpur ( IIT Kanpur ), The University of North Carolina at Chapel Hill, Université de Bonn, Wellcome Trust Sanger Institute, Harvard University School of Public Health, Czech Academy of Sciences [Prague] ( ASCR ), deCODE genetics, University of Groningen [Groningen]-University Medical Center Groningen-Beatrix Children's Hospital-Groningen Research Institute for Asthma and COPD, Yale School of Medicine, National Heart and Lung Institute ( NHLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, University Medical Center Groningen, University of Cambridge [UK] ( CAM ), Wellcome Trust Centre for Human Genetics, University of Pisa [Pisa], University of Cambridge [UK] ( CAM ) -Institute of Metabolic Science, German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), University of Otago, University of Greifswald, University College of London [London] ( UCL ), National Institute for Health and Welfare, Queen's University [Belfast] ( QUB ), University of Hawaii at Manoa ( UHM ), University of Gothenburg ( GU ) -Institute of Medicine, Recherches en Psychopathologie, nouveaux symptômes et lien social ( EA 4050 ), Université de Poitiers-Université de Brest ( UBO ) -Université Catholique de l'Ouest-Université de Rennes 2 ( UR2 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Institut de biologie de Lille - IBL ( IBLI ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Finland Institute for Molecular Medicine ( FIMM ), Georgia Prevention Institute, Netherlands Consortium for Healthy Aging, Helmholtz-Zentrum München ( HZM ), National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Massachusetts General Hospital, Children's Hospital, Boston, Broad Institute, Cambridge, MA, The University of North Carolina at Chapel Hill-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, Shungin D, Winkler TW, Adipogen, Consortium, Cardiogramplusc4d, Consortium, Ckdgen, Consortium, Gefos, Consortium, Genie, Consortium, Glgc, Icbp, International, Endogene Consortium, Lifelines, Cohort Study, Magic, Investigator, Muther, Consortium, Consortium, Page, ReproGen Consortium, Amouyel P, D'Adamo, ADAMO PIO, Gasparini, Paolo, Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Hypponen, Elina, Mohlke, Karen L, ADIPOGEN Consortium, Int Endogene Consortium, Lee Kong Chian School of Medicine (LKCMedicine), Epidemiologie, RS: CARIM - R3.02 - Hypertension and target organ damage, Université de Tours-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), 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, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, 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Smith, J, Stacey, S, Starr, J, Stathopoulou, M, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Wallaschofski, H, Widen, E, Wijnands van Gent, C, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Feenstra, B, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Easton, D, Foroud, T, Geller, F, Kilpeläinen, T, Li, S, Melbye, M, Murray, J, Murray, S, Ness, A, Northstone, K, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segrè, A, Sovio, U, Srinivasan, S, Tammesoo, M, Tyrer, J, Weedon, M, Young, L, Bierut, L, Boyd, H, Psychiatry, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
- Subjects
Adipose Tissue/metabolism ,Male ,genetic association ,subcutaneous fat ,Transcription, Genetic ,Adipocytes ,Adipogenesis ,Adipose Tissue ,Age Factors ,Body Mass Index ,Continental Population Groups ,Epigenesis, Genetic ,Europe ,Female ,Genome, Human ,Humans ,Insulin ,Insulin Resistance ,Models, Biological ,Neovascularization, Physiologic ,Obesity ,Polymorphism, Single Nucleotide ,Quantitative Trait Loci ,Sex Characteristics ,Waist-Hip Ratio ,Body Fat Distribution ,Genome-Wide Association Study ,Multidisciplinary ,Insulin Resistance/genetics ,Genome-wide association study ,Continental Population Groups/genetics ,genetic analysis ,heritability ,gene cluster ,Science::Biological sciences::Human anatomy and physiology [DRNTU] ,0302 clinical medicine ,high density lipoprotein cholesterol ,Models ,genetics [Insulin Resistance] ,histone modification ,Age Factor ,insulin receptor ,0303 health sciences ,Adipocyte ,Human/genetics ,CARDIOGRAMplusC4D Consortium ,ADIPOGENIC DIFFERENTIATION ,genetic correlation ,body fat ,Continental Population Group ,priority journal ,5 trisphosphate 3 phosphatase ,GEFOS Consortium ,meta analysis (topic) ,Science & Technology - Other Topics ,ddc:500 ,transcription regulation ,Adipogenesis/genetics ,Single Nucleotide/genetics ,Human ,medicine.medical_specialty ,Waist ,phosphatidylinositol 3 ,European ,ta3111 ,genetic regulation ,Article ,developmental biology ,03 medical and health sciences ,MAGIC Investigators ,transcription initiation site ,SDG 3 - Good Health and Well-being ,Genetic ,genomics ,GLYCEMIC TRAITS ,genetics [Continental Population Groups] ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Physiologic ,genetics [Adipogenesis] ,Adipocytes/metabolism ,Europe/ethnology ,Genome, Human/genetics ,Insulin/metabolism ,Neovascularization, Physiologic/genetics ,Obesity/genetics ,Polymorphism, Single Nucleotide/genetics ,Quantitative Trait Loci/genetics ,Transcription, Genetic/genetics ,Genetic/genetics ,Adipogenesi ,Science & Technology ,adiponectin ,[ SDV ] Life Sciences [q-bio] ,vasculotropin ,genetics [Quantitative Trait Loci] ,ta1184 ,Racial Groups ,ta1182 ,gene mapping ,ta3121 ,triacylglycerol blood level ,medicine.disease ,Biological ,major clinical study ,amino acid sequence ,metabolism [Insulin] ,Endocrinology ,metabolism [Adipocytes] ,genetic loci, insulin, body fat ,GLGC ,International Endogene Consortium ,metabolism [Adipose Tissue] ,Body mass index ,HUMAN HEIGHT ,Epigenesis ,LifeLines Cohort Study ,ReproGen Consortium ,BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA ,tissue level ,Physiologic/genetics ,[SDV]Life Sciences [q-bio] ,Medizin ,Adipose tissue ,low density lipoprotein cholesterol ,PAGE Consortium ,COMMON SNPS ,angiogenesis ,Waist–hip ratio ,genetics [Obesity] ,MESH: Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio ,single nucleotide polymorphism ,fat ,genetic variability ,molecular biology ,body mass index (BMI) ,ethnology [Europe] ,peroxisome proliferator activated receptor ,2. Zero hunger ,Genetics ,Genome ,Single Nucleotide ,waist circumference ,insulin ,phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase ,triacylglycerol ,vasculotropin, developmental biology ,gene expression ,genome ,numerical model, adipocyte ,adipose tissue ,body fat distribution ,body mass ,female ,gene locus ,gene structure ,hip circumference ,human ,insulin resistance ,lipoprotein blood level ,male ,obesity ,protein protein interaction ,sex difference ,waist hip ratio ,Multidisciplinary Sciences ,genetics [Transcription, Genetic] ,genetics [Polymorphism, Single Nucleotide] ,ADIPOGen Consortium ,genetics [Neovascularization, Physiologic] ,Transcription ,SUSCEPTIBILITY LOCI ,General Science & Technology ,ICBP ,030209 endocrinology & metabolism ,Biology ,adipocyte ,MESH : Adipocytes/metabolism Adipogenesis/genetics Adipose Tissue/metabolism* Age Factors Body Fat Distribution* Body Mass Index Continental Population Groups/genetics Epigenesis, Genetic Europe/ethnology Female Genome, Human/genetics Genome-Wide Association Study* Humans Insulin/metabolism* Insulin Resistance/genetics Male Models, Biological Neovascularization, Physiologic/genetics Obesity/genetics Polymorphism, Single Nucleotide/genetics Quantitative Trait Loci/genetics* Sex Characteristics Transcription, Genetic/genetics Waist-Hip Ratio ,MESENCHYMAL STEM-CELLS ,GENIE Consortium ,SEXUAL-DIMORPHISM ,Insulin resistance ,Internal medicine ,medicine ,genetics [Genome, Human] ,ABDOMINAL ADIPOSITY ,Neovascularization ,030304 developmental biology ,FALSE DISCOVERY ,CKDGen Consortium ,Sex Characteristic ,MuTHER Consortium ,numerical model - 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
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- 2015
11. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour
- Author
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Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Johannesson, Magnus, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chris, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, Day, Felix R., Mills, M. C., Tropf, F. C., Brazel, D. M., van Zuydam, N., Vaez, A., Agbessi, M., Ahsan, H., Alves, I., Andiappan, A. K., Arindrarto, W., Awadalla, P., Battle, A., Beutner, F., Jan Bonder, M., Boomsma, D. I., Christiansen, M. W., Claringbould, A., Deelen, P., Esko, T., Fave, M. -J., Franke, L., Frayling, T., Gharib, S. A., Gibson, G., Heijmans, B. T., Hemani, G., Jansen, R., Kahonen, M., Kalnapenkis, A., Kasela, S., Kettunen, J., Kim, Y., Kirsten, H., Kovacs, P., Krohn, K., Kronberg, J., Kukushkina, V., Kutalik, Z., Lee, B., Lehtimaki, T., Loeffler, M., Marigorta, U. M., Mei, H., Milani, L., Montgomery, G. W., Muller-Nurasyid, M., Nauck, M., Nivard, M. G., Penninx, B. W. J. H., Perola, M., Pervjakova, N., Pierce, B. L., Powell, J., Prokisch, H., Psaty, B. M., Raitakari, O. T., Ripatti, S., Rotzschke, O., Rueger, S., Saha, A., Scholz, M., Schramm, K., Seppala, I., Slagboom, E. P., Stehouwer, C. D. A., Stumvoll, M., Sullivan, P., 't Hoen, P. A. C., Teumer, A., Thiery, J., Tong, L., Tonjes, A., van Dongen, J., van Iterson, M., van Meurs, J., Veldink, J. H., Verlouw, J., Visscher, P. M., Volker, U., Vosa, U., Westra, H. -J., Wijmenga, C., Yaghootkar, H., Yang, J., Zeng, B., Zhang, F., van Greevenbroek, M. M. J., Schalkwijk, C. G., Deelen, J., van Heemst, D., van Duijn, C. M., Hofman, B. A., Isaacs, A., Uitterlinden, A. G., Verbiest, M., Suchiman, H. E. D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Bot, J., Zhernakova, D. V., Luijk, R., Bonder, M. J., Swertz, M. A., van Zwet, E. W., Akimova, E. T., Bergmann, S., Boardman, J. D., Buring, J. E., Cesarini, D., Chasman, D. I., Chavarro, J. E., Cocca, M., Concas, M. P., Davey-Smith, G., Davies, G., Deary, I. J., Gaskins, A. J., de Geus, E. J. C., Gieger, C., Girotto, G., Grabe, H. J., Gunderson, E. P., Harris, K. M., Hartwig, F. P., He, C., Homuth, G., Horta, B. L., Jan Hottenga, J., Huang, H., Hyppӧnen, E., Ikram, M. A., Johannesson, M., Kamali, Z., Kavousi, M., Kraft, P., Kuhnel, B., Langenberg, C., Study, L. C., Lind, P. A., Luan, J., Magi, R., Magnusson, P. K. E., Mahajan, A., Martin, N. G., Mbarek, H., Mccarthy, M. I., Mcmahon, G., Mcqueen, M. B., Medland, S. E., Meitinger, T., Metspalu, A., Mihailov, E., Missmer, S. A., Mollegaard, S., Mook-Kanamori, D. O., Morgan, A., van der Most, P. J., de Mutsert, R., Noordam, R., Power, C., Redmond, P., Rich-Edwards, J. W., Ridker, P. M., Rietveld, C. A., Ring, S. M., Rose, L. M., Rueedi, R., Stefansson, K., Stockl, D., Strauch, K., Thurik, A. R., Timpson, N. J., Turman, C., Wareham, N. J., Willemsen, G., Zhao, J. H., Pers, T. H., Snieder, H., Perry, J. R. B., Ong, K. K., den Hoed, M., Barban, N., Day, F. R., Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Hyppӧnen, Elina, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Consortium, eQTLGen, Consortium, BIOS, Consortium, Human Reproductive Behaviour, Mahajan, A, McCarthy, MI, Mills, Melinda C., Tropf, Felix C., Brazel, David M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Marku, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Jori, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthij, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Ikram, M. Arfan, Johannesson, Magnu, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thoma, Metspalu, Andre, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chri, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Dori, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Perry, John R. B., Ong, Ken K., Day, Felix R., Sociology [until 2010], Biological Psychology, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Management and Organisation, Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Neurology, Applied Economics, and Life Course Epidemiology (LCE)
- Subjects
Male ,demography ,genetic variants ,reproductive biology ,externalising behavior ,environmental effects ,Disease ,Genome-wide association studies ,Behavioral Neuroscience ,0302 clinical medicine ,genetics ,media_common ,fertility ,0303 health sciences ,Reproduction ,Incidence (epidemiology) ,Coitus ,Age Factors ,Longevity ,sexual intercourse ,health ,Spermatid differentiation ,Single Nucleotide ,Reproduction/genetics ,3. Good health ,Behavioural genetics ,Parturition/genetics ,Female ,infertility ,Infertility ,genetic variant ,Adolescent ,Social Psychology ,media_common.quotation_subject ,Experimental and Cognitive Psychology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Reproductive biology ,medicine ,Humans ,Polymorphism ,behavioural genetics ,first sexual intercourse ,Genetic Association Studies ,Demography ,030304 developmental biology ,Parturition ,Coitus/physiology ,medicine.disease ,externalising behaviour ,Sexual intercourse ,Fertility ,age ,030217 neurology & neurosurgery ,first birth - Abstract
Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.
- Published
- 2021
12. The trans-ancestral genomic architecture of glycemic traits
- Author
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Albertine J. Oldehinkel, Wieland Kiess, Xueling Sim, Norihiro Kato, Philippe Froguel, Astrid van Hylckama Vlieg, Josée Dupuis, Nanette R. Lee, Symen Ligthart, Harry Campbell, Marta E. Alarcón-Riquelme, P. Eline Slagboom, Massimo Mangino, Tian Xie, Niek Verweij, James B. Meigs, Chaolong Wang, Michael Y. Tsai, Erik Ingelsson, Colin N. A. Palmer, Erik B. van den Akker, Fumihiko Matsuda, Rainer Rauramaa, Yi-Cheng Chang, Lars Lind, Stefan R. Bornstein, Mandy Vogel, Sven Bergmann, Ya X. Wang, Ching-Ti Liu, Annette Schürmann, Michael Boehnke, David J. Porteous, Kazuya Setoh, Qibin Qi, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Claire J. Steves, Jun Liu, Leslie A. Lange, Noël P. Burtt, Diana Kuh, Cassandra N. Spracklen, Ken K. Ong, Charumathi Sabanayagam, Jost B. Jonas, Ele Ferrannini, Lawrence J. Beilin, Qing Duan, Blair H. Smith, Isobel D. Stewart, Alexander P. Reiner, Simon P. Mooijaart, Tim D. Spector, Paul W. Franks, E. Shyong Tai, Mark I. McCarthy, Anna L. Gloyn, D.I. Boomsma, Dennis Raven, Nicholas J. Timpson, Rona J. Strawbridge, George Dedoussis, Susan Redline, Jaeyoung Hong, Harald Grallert, Jagadish Vangipurapu, Rico Rueedi, Diane M. Becker, Marian Beekman, Claudia P. Cabrera, Johannes Waage, Jin Fang Chai, Yii-Der Ida Chen, Graciela E. Delgado, Thibaud S. Boutin, Yang Hai, Yoriko Heianza, Wei Zhao, Andres Metspalu, Tien Yin Wong, Mila Desi Anasanti, Inger Njølstad, Hans Bisgaard, Valeriya Lyssenko, Denis Rybin, Wanqing Wen, Torben Hansen, James F. Wilson, Sameline Grimsgaard, Annette Peters, Michele K. Evans, Damia Noce, Sarah C. Nelson, May E. Montasser, Nan Wang, Geltrude Mingrone, Gudny Eiriksdottir, Nicholas J. Wareham, Fouad Kandeel, Linda S. Adair, Kelvin Lam, Jaana Lindström, Eco J. C. de Geus, Debbie A Lawlor, Sara M. Willems, Xu Lin, Harold Snieder, Matt J. Neville, Naveed Sattar, Chelsea K. Raulerson, Paul M. Ridker, Jer-Yuarn Wu, Weihua Zhang, H. Janaka de Silva, Jana V. van Vliet-Ostaptchouk, Elena Tremoli, Toru Nabika, Jing Hua Zhao, Vilmundur Gudnason, Tao Huang, Robert C. Kaplan, Sohee Han, Mohammad Hadi Zafarmand, Aaron Leong, Yen-Feng Chiu, Kumaraswamy Naidu Chitrala, Ivana Kolcic, Franco Giulianini, Tao Wang, Lu Qi, Stephan J. L. Bakker, Laura J Corbin, Zoltán Kutalik, Bruna Gigante, Willa A. Hsueh, Peter J. van der Most, Tin Louie, Yujie Wang, Stella Trompet, Fernando Rivideneira, Yasumasa Ohyagi, Lynne E. Wagenknecht, Jerry L. Nadler, Michael Stumvoll, Mark O. Goodarzi, Sahoko Ichihara, Jeffrey R. O'Connell, Tomohiro Katsuya, Giorgio Pistis, Alice Stanton, Sirkka Keinänen-Kiukaanniemi, Momoko Horikoshi, Honglan Li, Tanja G. M. Vrijkotte, Caroline Hayward, Karen L. Mohlke, Carola Marzi, Girish N. Nadkarni, Laura J. Rasmussen-Torvik, Alain G. Bertoni, Andrew R. Wood, Annique Claringbould, Mi Yeong Hwang, Hugh Watkins, Heikki A. Koistinen, Mattias Frånberg, Jani Heikkinen, Elizabeth Selvin, Donald W. Bowden, Abbas Dehghan, Christian Fuchsberger, Audrey Y. Chu, Kent D. Taylor, Katherine A. Kentistou, Johanna Kuusisto, Jingyi Tan, Huaixing Li, Eric Boerwinkle, Catharina A. Hartman, Archie Campbell, Kari E. North, Oluf Pedersen, Sölve Elmståhl, Emil V. R. Appel, Chang-Hsun Hsieh, Dennis O. Mook-Kanamori, Rob M. van Dam, Pontiano Kaleebu, Corri Black, Jennifer A. Brody, Bengt Sennblad, Shaofeng Huo, M. Larissa Avilés-Santa, Ruth J. F. Loos, Patricia B. Munroe, Chien-Hsiun Chen, Liang Sun, Zorayr Arzumanyan, Rebecca Rohde, Yasuharu Tabara, Albert V. Smith, Betina H. Thuesen, Niels Grarup, Jorgen Engmann, Tatijana Zemunik, M. Arfan Ikram, Marit E. Jørgensen, Christian Herder, Ching-Yu Cheng, Serena Sanna, Damiano Baldassarre, Tarunveer S. Ahluwalia, Mark J. Caulfield, Anne Ndungu, Carl D. Langefeld, Lisa R. Yanek, Luigi Ferrucci, Ananda R. Wickremasinghe, Raymond Noordam, Trevor A. Mori, Tom Wilsgaard, Mika Kivimäki, Rita R. Kalyani, Alan B. Zonderman, Veronique Vitart, Patricia A. Peyser, Shuiqing Lai, Richa Saxena, Li-Ching Chang, Karin Leander, Wei Huang, Peter Vollenweider, Tanya M. Teslovich, Ying Wu, Shufa Du, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Stephen C. J. Parker, Tamar Sofer, Winfried März, Sharon L.R. Kardia, Peter K. Joshi, Neil R. Robertson, Anny H. Xiang, Fumihiko Takeuchi, N. Amin, Jouke-Jan Hottenga, Carol A. Wang, Stefan Gustafsson, Jung Ho Gong, Penny Gordon-Larsen, Yu-Tang Gao, Abhishek Nag, Gonneke Willemsen, Michael A. Province, Aliki-Eleni Farmaki, Segun Fatumo, Antje Körner, Pim van der Harst, Marie Loh, Kei Hang Katie Chan, Gonçalo R. Abecasis, Nicholette D. Palmer, Simin Liu, Ishminder K. Kooner, Javier Gayán, Arne Astrup, Laura J. Scott, Erwin P. Bottinger, Andrew Wong, Inga Prokopenko, Ping An, Markku Laakso, Matthias Blüher, Susan R. Heckbert, Thomas A. Buchanan, Tatsuaki Matsubara, Andrew P. Morris, Brian H. Chen, Kristi Läll, Teresa Tusie, Timo A. Lakka, Jie Yao, Michael Preuss, Teemu Kuulasmaa, Carlos Lorenzo, Stephen S. Rich, Marie Lauzon, Laura M. Raffield, Pankow S. James, Takahisa Kawaguchi, Kathleen A. Ryan, Wei Zheng, Igor Rudan, Thomas Sparsø, Hugoline G. de Haan, Sandosh Padmanabhan, Richard M. Watanabe, Alicia Huerta-Chagoya, Anette P. Gjesing, Andrew A. Hicks, Richard N. Bergman, Mitsuhiro Yokota, Heather M. Stringham, Bruce M. Psaty, Jian'an Luan, Anuj Goel, Eleanor Wheeler, Masahiro Nakatochi, Young-Jin Kim, Xiao-Ou Shu, Mickaël Canouil, Robert A. Scott, Marika Kaakinen, Mari Nelis, Adolfo Correa, Jaspal S. Kooner, Michiya Igase, Anubha Mahajan, Peter E. H. Schwarz, Craig E. Pennell, Claudia Schurmann, Xiaoran Chai, Ji Chen, Lori L. Bonnycastle, Peter S. Sever, Thorkild I. A. Sørensen, André G. Uitterlinden, Ilja M. Nolte, Gaëlle Marenne, Timothy M. Frayling, Bong-Jo Kim, Kerrin S. Small, Cecilia M. Lindgren, Bernhard O. Böhm, Shih-Yi Lin, Katharina E. Schraut, Cornelia M. van Duijn, Sanghoon Moon, Mark Walker, Chiea Chuen Khor, Ruifang Li-Gao, Qiuyin Cai, Neil Schneiderman, Ko Willems van Dijk, Ozren Polasek, W. Craig Johnson, Dermot F. Reilly, Inês Barroso, Anke Tönjes, Manjinder S. Sandhu, Wen B. Wei, Jose C. Florez, Lorraine Southam, Leif Groop, Lawrence F. Bielak, Peter Kovacs, Jianjun Liu, Jouko Saramies, Helen R. Warren, Man Li, Daniel I. Chasman, Eleftheria Zeggini, Xiaoshuai Zhang, Loic Yengo, Shi Jinxiu, Jirong Long, Xiuqing Guo, Meena Kumari, Leslie J. Raffel, Jill M. Norris, Henrik Vestergaard, Jing He, Peter P. Pramstaller, Diana van Heemst, Kevin Sandow, Marjo-Ritta Jarvelin, Carlos A. Aguilar-Salinas, Peitao Wu, Hortensia Moreno-Macías, Jerome I. Rotter, Kathryn Roll, Frits R. Rosendaal, Bernardo L. Horta, Heming Wang, Fernando Pires Hartwig, Richard A. Jensen, Matti Uusitupa, Rozenn N. Lemaitre, Paul R. H. J. Timmers, Timo Saaristo, Jaakko Tuomilehto, Reedik Mägi, Debashree Ray, J. Wouter Jukema, Claudia Langenberg, Marcus E. Kleber, Francis S. Collins, Klaus Bønnelykke, Lenore J. Launer, Arushi Varshney, Anders Hamsten, European Commission, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanger Institute, Wellcome Trust, Marenne, Gaëlle [0000-0002-4363-7170], Varshney, Arushi [0000-0001-9177-9707], Corbin, Laura J [0000-0002-4032-9500], Parker, Stephen CJ [0000-0001-8122-0117], Langenberg, Claudia [0000-0002-5017-7344], Wheeler, Eleanor [0000-0002-8616-6444], Morris, Andrew P [0000-0002-6805-6014], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Lifelines Cohort Study, Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC), de Haan, H.G., van den Akker, E., van der Most, P.J., de Geus, EJC, van Dam, R.M., van Heemst, D., van Hylckama Vlieg, A., van Willems van Dijk, K., de Silva, H.J., van der Harst, P., van Duijn, C., Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Leif Groop Research Group, HUS Internal Medicine and Rehabilitation, Department of Medicine, Department of Biochemistry and Developmental Biology, Helsinki University Hospital Area, University of Helsinki, Clinicum, Department of Public Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Physiology, AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, APH - Mental Health, Nutrition and Health, APH - Methodology, Epidemiology and Data Science, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Public and occupational health, Epidemiology, Internal Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Cardiovascular Centre (CVC)
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Blood Glucose ,Disease risk ,Multifactorial Inheritance ,Glycated Hemoglobin A ,[SDV]Life Sciences [q-bio] ,Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) ,LOCI ,Genome-wide association study ,Type 2 diabetes ,VARIANTS ,GLUCOSE ,Epigenesis, Genetic ,chemistry.chemical_compound ,0302 clinical medicine ,Mechanisms ,WIDE ASSOCIATION ,genetics ,Gene-expression ,HEMOGLOBIN ,ComputingMilieux_MISCELLANEOUS ,11 Medical and Health Sciences ,GENE-EXPRESSION ,Genetics ,Genetics & Heredity ,0303 health sciences ,INSULIN-RESISTANCE ,Genome ,Loci ,1184 Genetics, developmental biology, physiology ,Variants ,ALSPAC ,Physical Chromosome Mapping ,Life Sciences & Biomedicine ,Human ,Quantitative Trait Loci ,Wide association study ,Biology ,Quantitative trait locus ,Article ,White People ,diseases ,MECHANISMS ,Quantitative Trait ,03 medical and health sciences ,Insulin resistance ,Quantitative Trait, Heritable ,SDG 3 - Good Health and Well-being ,Genetic ,Lifelines Cohort Study ,Diabetes mellitus ,medicine ,Humans ,Hemoglobin ,Heritable ,METAANALYSIS ,Alleles ,030304 developmental biology ,Genetic association ,Glycemic ,Glycated Hemoglobin ,Science & Technology ,Genome, Human ,Whites ,Gene Expression Profiling ,DISEASE RISK ,Settore MED/13 - ENDOCRINOLOGIA ,Insulin-resistance ,06 Biological Sciences ,medicine.disease ,Glucose ,chemistry ,Blood Glucose/genetics ,European Continental Ancestry Group/genetics ,Genome-Wide Association Study ,Glycated Hemoglobin A/metabolism ,Multifactorial Inheritance/genetics ,Quantitative Trait Loci/genetics ,Glycated hemoglobin ,030217 neurology & neurosurgery ,Meta analysis ,Epigenesis ,Developmental Biology - 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-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.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.
- Published
- 2021
13. Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids
- Author
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Bentley, Amy R, Sung, Yun J, Brown, Michael R, Winkler, Thomas W, Kraja, Aldi T, Ntalla, Ioanna, Schwander, Karen, Chasman, Daniel I, Lim, Elise, Deng, Xuan, Guo, Xiuqing, Liu, Jingmin, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Baker, Jenna, Chen, Guanjie, Aschard, Hugues, Bartz, Traci M, Ding, Jingzhong, Dorajoo, Rajkumar, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Zhao, Wei, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Hung, Yi-Jen, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Prins, Bram, Riaz, Muhammad, Robino, Antonietta, Said, M Abdullah, Schupf, Nicole, Scott, Robert A, Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Tzung-Dau, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Xiang, Yong-Bing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Adeyemo, Adebowale, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Arzumanyan, Zorayr, Aung, Tin, Ballantyne, Christie, Barr, R Graham, Bielak, Lawrence F, Boerwinkle, Eric, Bottinger, Erwin P, Broeckel, Ulrich, Brown, Morris, Cade, Brian E, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Christensen, Kaare, Concas, Maria Pina, Connell, John M, de las Fuentes, Lisa, de Silva, H Janaka, de Vries, Paul S, Doumatey, Ayo, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Floyd, James S, Forouhi, Nita G, Forrester, Terrence, Friedlander, Yechiel, Gandin, Ilaria, Gao, He, Ghanbari, Mohsen, Gharib, Sina A, Gigante, Bruna, Giulianini, Franco, Grabe, Hans J, Gu, C Charles, Harris, Tamara B, Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E, Ikram, M Arfan, Jia, Yucheng, Joehanes, Roby, Johnson, Craig, Jonas, Jost Bruno, Justice, Anne E, Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O, Koh, Woon-Puay, Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E, Kritchevsky, Stephen B, Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lehne, Benjamin, Lewis, Cora E, Li, Yize, Liang, Jingjing, Lin, Shiow, Liu, Ching-Ti, Liu, Jianjun, Liu, Kiang, Loh, Marie, Lohman, Kurt K, Louie, Tin, Luzzi, Anna, Magi, Reedik, Mahajan, Anubha, Manichaikul, Ani W, McKenzie, Colin A, Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L, Momozawa, Yukihide, Morris, Andrew P, Murray, Alison D, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, North, Kari E, O'Connell, Jeffrey R, Palmer, Nicholette D, Papanicolau, George J, Pedersen, Nancy L, Peters, Annette, Peyser, Patricia A, Polasek, Ozren, Poulter, Neil, Raitakari, Olli T, Reiner, Alex P, Renstrom, Frida, Rice, Treva K, Rich, Stephen S, Robinson, Jennifer G, Rose, Lynda M, Rosendaal, Frits R, Rudan, Igor, Schmidt, Carsten O, Schreiner, Pamela J, Scott, William R, Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Jennifer A, Snieder, Harold, Starr, John M, Strauch, Konstantin, Stringham, Heather M, Tan, Nicholas YQ, Tang, Hua, Taylor, Kent D, Teo, Yik Ying, Tham, Yih Chung, Tiemeier, Henning, Turner, Stephen T, Uitterlinden, Andre G, van Heemst, Diana, Waldenberger, Melanie, Wang, Heming, Wang, Lan, Wang, Lihua, Wei, Wen Bin, Williams, Christine A, Sr, Wilson Gregory, Wojczynski, Mary K, Yao, Jie, Young, Kristin, Yu, Caizheng, Yuan, Jian-Min, Zhou, Jie, Zonderman, Alan B, Becker, Diane M, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Cooper, Richard S, de Faire, Ulf, Deary, Ian J, Elliott, Paul, Esko, Tonu, Farrall, Martin, Franks, Paul W, Freedman, Barry I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L, Juang, Jyh-Ming Jimmy, Kamatani, Yoichiro, Kammerer, Candace M, Kato, Norihiro, Kooner, Jaspal S, Laakso, Markku, Laurie, Cathy C, Lee, I-Te, Lehtimaki, Terho, Magnusson, Patrik KE, Oldehinkel, Albertine J, Penninx, Brenda WJH, Pereira, Alexandre C, Rauramaa, Rainer, Redline, Susan, Samani, Nilesh J, Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E, Wang, Jun-Sing, Wang, Ya Xing, Wareham, Nicholas J, Watkins, Hugh, Weir, David R, Wickremasinghe, Ananda R, Wu, Tangchun, Zeggini, Eleftheria, Zheng, Wei, Bouchard, Claude, Evans, Michele K, Gudnason, Vilmundur, Kardia, Sharon LR, Liu, Yongmei, Psaty, Bruce M, Ridker, Paul M, van Dam, Rob M, Mook-Kanamori, Dennis O, Fornage, Myriam, Province, Michael A, Kelly, Tanika N, Fox, Ervin R, Hayward, Caroline, van Duijn, Cornelia M, Tai, E Shyong, Wong, Tien Yin, Loos, Ruth JF, Franceschini, Nora, Rotter, Jerome I, Zhu, Xiaofeng, Bierut, Laura J, Gauderman, W James, Rice, Kenneth, Munroe, Patricia B, Morrison, Alanna C, Rao, Dabeeru C, Rotimi, Charles N, Cupples, L Adrienne, Consortium, COGENT-Kidney, Consortium, EPIC-InterAct, Grp, Understanding Soc Sci, Cohort, Lifelines, National Institutes of Health [Bethesda] (NIH), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), The University of Texas Health Science Center at Houston (UTHealth), Universität Regensburg (UR), Queen Mary University of London (QMUL), Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Public Health [Boston], Boston University [Boston] (BU), Los Angeles Biomedical Research Institute (LA BioMed), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Singapore Eye Research Institute [Singapore] (SERI), Duke-NUS Medical School [Singapore], National University of Singapore (NUS), Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Edinburgh, University of Mississippi Medical Center (UMMC), University of Georgia [USA], Leiden University Medical Center (LUMC), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Harvard T.H. Chan School of Public Health, University of Washington [Seattle], Wake Forest University, Genome Institute of Singapore (GIS), Massachusetts General Hospital [Boston], Pennington Biomedical Research Center, Louisiana State University (LSU), Icelandic Heart Association [Kopavogur, Iceland] (IHA), University of Iceland [Reykjavik], University of Michigan [Ann Arbor], University of Michigan System, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Tartu, Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Imperial College London, University of Ioannina, University of Oxford [Oxford], University of Groningen [Groningen], Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), University of Bristol [Bristol], Huazhong University of Science and Technology [Wuhan] (HUST), Universidade de São Paulo Medical School (FMUSP), Case Western Reserve University [Cleveland], University of Southern California (USC), This project was largely supported by a grant from the US National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL118305) and by the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health through the Center for Research on Genomics and Global Health (CRGGH). The CRGGH is supported by the National Human Genome Research Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Center for Information Technology, and the Office of the Director at the National Institutes of Health (Z01HG200362)., Bentley, Ar, Sung, Yj, Brown, Mr, Winkler, Tw, Kraja, At, Ntalla, I, Schwander, K, Chasman, Di, Lim, E, Deng, X, Guo, X, Liu, J, Lu, Y, Cheng, Cy, Sim, X, Vojinovic, D, Huffman, Je, Musani, Sk, Li, C, Feitosa, Mf, Richard, Ma, Noordam, R, Baker, J, Chen, G, Aschard, H, Bartz, Tm, Ding, J, Dorajoo, R, Manning, Ak, Rankinen, T, Smith, Av, Tajuddin, Sm, Zhao, W, Graff, M, Alver, M, Boissel, M, Chai, Jf, Chen, X, Divers, J, Evangelou, E, Gao, C, Goel, A, Hagemeijer, Y, Harris, Se, Hartwig, Fp, He, M, Horimoto, Arvr, Hsu, Fc, Hung, Yj, Jackson, Au, Kasturiratne, A, Komulainen, P, Kühnel, B, Leander, K, Lin, Kh, Luan, J, Lyytikäinen, Lp, Matoba, N, Nolte, Im, Pietzner, M, Prins, B, Riaz, M, Robino, A, Said, Ma, Schupf, N, Scott, Ra, Sofer, T, Stancáková, A, Takeuchi, F, Tayo, Bo, van der Most, Pj, Varga, Tv, Wang, Td, Wang, Y, Ware, Eb, Wen, W, Xiang, Yb, Yanek, Lr, Zhang, W, Zhao, Jh, Adeyemo, A, Afaq, S, Amin, N, Amini, M, Arking, De, Arzumanyan, Z, Aung, T, Ballantyne, C, Barr, Rg, Bielak, Lf, Boerwinkle, E, Bottinger, Ep, Broeckel, U, Brown, M, Cade, Be, Campbell, A, Canouil, M, Charumathi, S, Chen, Yi, Christensen, K, COGENT-Kidney, Consortium, Concas, Mp, Connell, Jm, de Las Fuentes, L, de Silva, Hj, de Vries, P, Doumatey, A, Duan, Q, Eaton, Cb, Eppinga, Rn, Faul, Jd, Floyd, J, Forouhi, Ng, Forrester, T, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, M, Gharib, Sa, Gigante, B, Giulianini, F, Grabe, Hj, Gu, Cc, Harris, Tb, Heikkinen, S, Heng, Ck, Hirata, M, Hixson, Je, Ikram, Ma, EPIC-InterAct, Consortium, Jia, Y, Joehanes, R, Johnson, C, Jonas, Jb, Justice, Ae, Katsuya, T, Khor, Cc, Kilpeläinen, To, Koh, Wp, Kolcic, I, Kooperberg, C, Krieger, Je, Kritchevsky, Sb, Kubo, M, Kuusisto, J, Lakka, Ta, Langefeld, Cd, Langenberg, C, Launer, Lj, Lehne, B, Lewis, Ce, Li, Y, Liang, J, Lin, S, Liu, Ct, Liu, K, Loh, M, Lohman, Kk, Louie, T, Luzzi, A, Mägi, R, Mahajan, A, Manichaikul, Aw, Mckenzie, Ca, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, Kl, Momozawa, Y, Morris, Ap, Murray, Ad, Nalls, Ma, Nauck, M, Nelson, Cp, North, Ke, O'Connell, Jr, Palmer, Nd, Papanicolau, Gj, Pedersen, Nl, Peters, A, Peyser, Pa, Polasek, O, Poulter, N, Raitakari, Ot, Reiner, Ap, Renström, F, Rice, Tk, Rich, S, Robinson, Jg, Rose, Lm, Rosendaal, Fr, Rudan, I, Schmidt, Co, Schreiner, Pj, Scott, Wr, Sever, P, Shi, Y, Sidney, S, Sims, M, Smith, Ja, Snieder, H, Starr, Jm, Strauch, K, Stringham, Hm, Tan, Nyq, Tang, H, Taylor, Kd, Teo, Yy, Tham, Yc, Tiemeier, H, Turner, St, Uitterlinden, Ag, Understanding Society Scientific, Group, van Heemst, D, Waldenberger, M, Wang, H, Wang, L, Wei, Wb, Williams, Ca, Wilson, G Sr, Wojczynski, Mk, Yao, J, Young, K, Yu, C, Yuan, Jm, Zhou, J, Zonderman, Ab, Becker, Dm, Boehnke, M, Bowden, Dw, Chambers, Jc, Cooper, R, de Faire, U, Deary, Ij, Elliott, P, Esko, T, Farrall, M, Franks, Pw, Freedman, Bi, Froguel, P, Gasparini, P, Gieger, C, Horta, Bl, Juang, Jj, Kamatani, Y, Kammerer, Cm, Kato, N, Kooner, J, Laakso, M, Laurie, Cc, Lee, It, Lehtimäki, T, Lifelines, Cohort, Magnusson, Pke, Oldehinkel, Aj, Penninx, Bwjh, Pereira, Ac, Rauramaa, R, Redline, S, Samani, Nj, Scott, J, Shu, Xo, van der Harst, P, Wagenknecht, Le, Wang, J, Wang, Yx, Wareham, Nj, Watkins, H, Weir, Dr, Wickremasinghe, Ar, Wu, T, Zeggini, E, Zheng, W, Bouchard, C, Evans, Mk, Gudnason, V, Kardia, Slr, Liu, Y, Psaty, Bm, Ridker, Pm, van Dam, Rm, Mook-Kanamori, Do, Fornage, M, Province, Ma, Kelly, Tn, Fox, Er, Hayward, C, van Duijn, Cm, Tai, E, Wong, Ty, Loos, Rjf, Franceschini, N, Rotter, Ji, Zhu, X, Bierut, Lj, Gauderman, Wj, Rice, K, Munroe, Pb, Morrison, Ac, Rao, Dc, Rotimi, Cn, Cupples, La., Luan, Jian'an [0000-0003-3137-6337], Pietzner, Maik [0000-0003-3437-9963], Zhao, Jing Hua [0000-0003-4930-3582], Forouhi, Nita [0000-0002-5041-248X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Home Office, Action on Hearing Loss, Imperial College Healthcare NHS Trust- BRC Funding, Medical Research Council (MRC), Universiteit Leiden, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), University of Oxford, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, and APH - Digital Health
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Male ,Linkage disequilibrium ,Blood lipids ,Genome-wide association study ,VARIANTS ,SUSCEPTIBILITY ,Environment interaction ,Genome ,Linkage Disequilibrium ,MESH: Genotype ,0302 clinical medicine ,MESH: Aged, 80 and over ,Genotype ,NICOTINE METABOLISM ,11 Medical and Health Sciences ,Genetics & Heredity ,Aged, 80 and over ,Genetics ,MESH: Aged ,0303 health sciences ,ARCHITECTURE ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,Genotype imputation ,MESH: Middle Aged ,CHOLESTEROL ,Smoking ,MESH: Life Style ,Lifelines Cohort ,Middle Aged ,Lipids ,3. Good health ,ENVIRONMENT INTERACTION ,GENOTYPE IMPUTATION ,RISK LOCI ,METAANALYSIS ,CIGARETTES ,Cholesterol ,MESH: Linkage Disequilibrium ,MESH: Young Adult ,Meta-analysis ,Genome-Wide Association Study/methods ,Smoking/blood ,Medical genetics ,Female ,EPIC-InterAct Consortium ,Life Sciences & Biomedicine ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,Adult ,Metaanalysi ,Understanding Society Scientific Group ,medicine.medical_specialty ,MESH: Smoking ,Adolescent ,Genomics ,COGENT-Kidney Consortium ,Biology ,Nicotine metabolism ,Risk loci ,Metaanalysis ,Cigarettes ,Article ,Young Adult ,03 medical and health sciences ,genomics ,medicine ,Humans ,Linkage Disequilibrium/genetics ,Life Style ,Aged ,030304 developmental biology ,MESH: Adolescent ,Science & Technology ,MESH: Humans ,Lipids/blood ,MESH: Adult ,06 Biological Sciences ,MESH: Lipids ,MESH: Male ,cardiovascular diseases ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,genome-wide association studies ,MESH: Genome-Wide Association Study ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,MESH: Female ,030217 neurology & neurosurgery ,Developmental Biology ,Genome-Wide Association Study - Abstract
The concentrations of high- and low-density lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 novel loci, some of which were detected only because the association differed by smoking status. Additionally, we demonstrated the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings., Editorial summary: A multi-ancestry genome-wide gene-smoking interaction study identifies 13 new loci associated with serum lipids.
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- 2019
14. Effects of Calcium, Magnesium, and Potassium concentrations on ventricular repolarization in unselected individuals
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Pedro Guatimosim Vidigal, Yongmei Liu, Alice Stanton, Kent D. Taylor, Thomas Meitinger, Vilmundur Gudnason, Massimo Mangino, Mario Pirastu, Nilesh J. Samani, Christopher Newton-Cheh, Xiuqing Guo, Bruno H. Stricker, Mortiz F. Sinner, Steven R. Cummings, Jennifer A. Brody, Antonio Luiz Pinho Ribeiro, Mark J. Caulfield, Bryan Kestenbaum, Dennis O. Mook-Kanamori, Jørgen K. Kanters, Kirill V. Tarasov, Martina Müller-Nurasyid, Luana Giatti, Elsayed Z. Soliman, Christian R. Juhl, Nuno R. Zilhão, Harold Snieder, Eric Campana, Mika Kähönen, Ginevra Biino, Raymond Noordam, Jun Ding, Chris H. L. Thio, Jerome I. Rotter, Torben Hansen, M. Abdullah Said, Francesco Cucca, Allan Linneberg, Nona Sotoodehnia, Niels Grarup, Peter S. Sever, James F. Wilson, André G. Uitterlinden, Xia Shen, Luisa Foco, Yong Qian, Christina Ellervik, Diana van Heemst, Antonietta Robino, Henry J. Lin, Konstantin Strauch, Patricia B. Munroe, Nabi Shah, Claus Graff, Daniel S. Evans, Peter J. van der Most, Stefan Weiss, Maria Pina Concas, Reem Salman, Hao Mei, Linda Repetto, Helen R. Warren, Peter K. Joshi, Susan R. Heckbert, Tim D. Spector, Sandhi Maria Barreto, Jie Yao, Marcus Dörr, Eulalia Catamo, Anna F. Dominiczak, Leo-Pekka Lyytikäinen, Giorgia Girotto, Peter P. Pramstaller, Gudny Eiriksdottir, J. Wouter Jukema, Paulo A. Lotufo, Colin N. A. Palmer, Andrew Tinker, James G. Wilson, Mary L. Biggs, Astrid Petersmann, Arie C. Maan, Peter S. Braund, Maria Fernanda Lima-Costa, Paraskevi Christofidou, Sandosh Padmanabhan, Adolfo Correa, Melanie Waldenberger, Alessandro De Grandi, Stefan Kääb, Cristian Pattaro, Annette Peters, William J Young, Alex S. F. Doney, Katharina Schramm, Terho Lehtimäki, Christopher P. Nelson, Martin Gögele, Marten E. van den Berg, Marco Brumat, Pim van der Harst, Niek Verweij, Simona Vaccargiu, Noordam, R, Young, Wj, Salman, R, Kanters, Jk, van den Berg, Me, van Heemst, D, Lin, Hj, Barreto, Sm, Biggs, Ml, Biino, G, Catamo, E, Concas, Mp, Ding, J, Evans, D, Foco, L, Grarup, N, Lyytikäinen, Lp, Mangino, M, Mei, H, van der Most, Pj, Müller-Nurasyid, M, Nelson, Cp, Qian, Y, Repetto, L, Said, Ma, Shah, N, Schramm, K, Vidigal, Pg, Weiss, S, Yao, J, Zilhao, Nr, Brody, Ja, Braund, P, Brumat, M, Campana, E, Christofidou, P, Caulfield, Mj, De Grandi, A, Dominiczak, Af, Doney, Asf, Eiriksdottir, G, Ellervik, C, Giatti, L, Gögele, M, Graff, C, Guo, X, van der Harst, P, Joshi, Pk, Kähönen, M, Kestenbaum, B, Lima-Costa, Mf, Linneberg, A, Maan, Ac, Meitinger, T, Padmanabhan, S, Pattaro, C, Peters, A, Petersmann, A, Sever, P, Sinner, Mf, Shen, X, Stanton, A, Strauch, K, Soliman, Ez, Tarasov, Kv, Taylor, Kd, Thio, Chl, Uitterlinden, Ag, Vaccargiu, S, Waldenberger, M, Robino, A, Correa, A, Cucca, F, Cummings, Sr, Dörr, M, Girotto, G, Gudnason, V, Hansen, T, Heckbert, Sr, Juhl, Cr, Kääb, S, Lehtimäki, T, Liu, Y, Lotufo, Pa, Palmer, Cna, Pirastu, M, Pramstaller, Pp, Ribeiro, Alp, Rotter, Ji, Samani, Nj, Snieder, H, Spector, Td, Stricker, Bh, Verweij, N, Wilson, Jf, Wilson, Jg, Jukema, Jw, Tinker, A, Newton-Cheh, Ch, Sotoodehnia, N, Mook-Kanamori, Do, Munroe, Pb, Warren, Hr., Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), and Epidemiology
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Male ,Cardiac & Cardiovascular Systems ,030204 cardiovascular system & hematology ,ELECTROCARDIOGRAM ,Electrocardiography ,0302 clinical medicine ,cohort studies ,Risk Factors ,Medicine ,Magnesium ,030212 general & internal medicine ,Correlation of Data ,1102 Cardiorespiratory Medicine and Haematology ,RISK ,education.field_of_study ,medicine.diagnostic_test ,ACTION-POTENTIAL DURATION ,ASSOCIATION ,Middle Aged ,COUNCIL ,electrocardiographic intervals ,Cardiovascular Diseases ,Cardiology ,Female ,epidemiology ,Electrical conduction system of the heart ,Cardiology and Cardiovascular Medicine ,Electrophysiologic Techniques, Cardiac ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Population ,electrolytes epidemiology ,meta-analysis ,chemistry.chemical_element ,electrolytes ,Calcium ,QT interval ,1117 Public Health and Health Services ,03 medical and health sciences ,QRS complex ,DISPERSION ,Heart Conduction System ,Internal medicine ,Humans ,PR interval ,education ,Science & Technology ,Cohort Studies ,Electrocardiographic Intervals ,Electrolytes ,Epidemiology ,Meta-analysis ,business.industry ,QT INTERVAL ,RESTING HEART-RATE ,Confidence interval ,REDUCTION ,chemistry ,Cardiovascular System & Hematology ,CONDUCTION ,Asymptomatic Diseases ,Potassium ,Cardiovascular System & Cardiology ,electrocardiographic interval ,business ,cohort studie - Abstract
BACKGROUND Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.OBJECTIVES This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.METHODS Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 +/- 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.RESULTS Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.CONCLUSIONS The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms. (C) 2019 by the American College of Cardiology Foundation.
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- 2019
15. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
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Symen Ligthart, Ahmad Vaez, Urmo Võsa, Maria G. Stathopoulou, Paul S. de Vries, Bram P. Prins, Peter J. Van der Most, Toshiko Tanaka, Elnaz Naderi, Lynda M. Rose, Ying Wu, Robert Karlsson, Maja Barbalic, Honghuang Lin, René Pool, Gu Zhu, Aurélien Macé, Carlo Sidore, Stella Trompet, Massimo Mangino, Maria Sabater-Lleal, John P. Kemp, Ali Abbasi, Tim Kacprowski, Niek Verweij, Albert V. Smith, Tao Huang, Carola Marzi, Mary F. Feitosa, Kurt K. Lohman, Marcus E. Kleber, Yuri Milaneschi, Christian Mueller, Mahmudul Huq, Efthymia Vlachopoulou, Leo-Pekka Lyytikäinen, Christopher Oldmeadow, Joris Deelen, Markus Perola, Jing Hua Zhao, Bjarke Feenstra, Marzyeh Amini, Jari Lahti, Katharina E. Schraut, Myriam Fornage, Bhoom Suktitipat, Wei-Min Chen, Xiaohui Li, Teresa Nutile, Giovanni Malerba, Jian’an Luan, Tom Bak, Nicholas Schork, Fabiola Del Greco M., Elisabeth Thiering, Anubha Mahajan, Riccardo E. Marioni, Evelin Mihailov, Joel Eriksson, Ayse Bilge Ozel, Weihua Zhang, Maria Nethander, Yu-Ching Cheng, Stella Aslibekyan, Wei Ang, Ilaria Gandin, Loïc Yengo, Laura Portas, Charles Kooperberg, Edith Hofer, Kumar B. Rajan, Claudia Schurmann, Wouter den Hollander, Tarunveer S. Ahluwalia, Jing Zhao, Harmen H.M. Draisma, Ian Ford, Nicholas Timpson, Alexander Teumer, Hongyan Huang, Simone Wahl, YongMei Liu, Jie Huang, Hae-Won Uh, Frank Geller, Peter K. Joshi, Lisa R. Yanek, Elisabetta Trabetti, Benjamin Lehne, Diego Vozzi, Marie Verbanck, Ginevra Biino, Yasaman Saba, Ingrid Meulenbelt, Jeff R. O’Connell, Markku Laakso, Franco Giulianini, Patrik K.E. Magnusson, Christie M. Ballantyne, Jouke Jan Hottenga, Grant W. Montgomery, Fernando Rivadineira, Rico Rueedi, Maristella Steri, Karl-Heinz Herzig, David J. Stott, Cristina Menni, Mattias Frånberg, Beate St. Pourcain, Stephan B. Felix, Tune H. Pers, Stephan J.L. Bakker, Peter Kraft, Annette Peters, Dhananjay Vaidya, Graciela Delgado, Johannes H. Smit, Vera Großmann, Juha Sinisalo, Ilkka Seppälä, Stephen R. Williams, Elizabeth G. Holliday, Matthijs Moed, Claudia Langenberg, Katri Räikkönen, Jingzhong Ding, Harry Campbell, Michele M. Sale, Yii-Der I. Chen, Alan L. James, Daniela Ruggiero, Nicole Soranzo, Catharina A. Hartman, Erin N. Smith, Gerald S. Berenson, Christian Fuchsberger, Dena Hernandez, Carla M.T. Tiesler, Vilmantas Giedraitis, David Liewald, Krista Fischer, Dan Mellström, Anders Larsson, Yunmei Wang, William R. Scott, Matthias Lorentzon, John Beilby, Kathleen A. Ryan, Craig E. Pennell, Dragana Vuckovic, Beverly Balkau, Maria Pina Concas, Reinhold Schmidt, Carlos F. Mendes de Leon, Erwin P. Bottinger, Margreet Kloppenburg, Lavinia Paternoster, Michael Boehnke, A.W. Musk, Gonneke Willemsen, David M. Evans, Pamela A.F. Madden, Mika Kähönen, Zoltán Kutalik, Magdalena Zoledziewska, Ville Karhunen, Stephen B. Kritchevsky, Naveed Sattar, Genevieve Lachance, Robert Clarke, Tamara B. Harris, Olli T. Raitakari, John R. Attia, Diana van Heemst, Eero Kajantie, Rossella Sorice, Giovanni Gambaro, Robert A. Scott, Andrew A. Hicks, Luigi Ferrucci, Marie Standl, Cecilia M. Lindgren, John M. Starr, Magnus Karlsson, Lars Lind, Jun Z. Li, John C. Chambers, Trevor A. Mori, Eco J.C.N. de Geus, Andrew C. Heath, Nicholas G. Martin, Juha Auvinen, Brendan M. Buckley, Anton J.M. de Craen, Melanie Waldenberger, Konstantin Strauch, Thomas Meitinger, Rodney J. Scott, Mark McEvoy, Marian Beekman, Cristina Bombieri, Paul M. Ridker, Karen L. Mohlke, Nancy L. Pedersen, Alanna C. Morrison, Dorret I. Boomsma, John B. Whitfield, David P. Strachan, Albert Hofman, Peter Vollenweider, Francesco Cucca, Marjo-Riitta Jarvelin, J. Wouter Jukema, Tim D. Spector, Anders Hamsten, Tanja Zeller, André G. Uitterlinden, Matthias Nauck, Vilmundur Gudnason, Lu Qi, Harald Grallert, Ingrid B. Borecki, Jerome I. Rotter, Winfried März, Philipp S. Wild, Marja-Liisa Lokki, Michael Boyle, Veikko Salomaa, Mads Melbye, Johan G. Eriksson, James F. Wilson, Brenda W.J.H. Penninx, Diane M. Becker, Bradford B. Worrall, Greg Gibson, Ronald M. Krauss, Marina Ciullo, Gianluigi Zaza, Nicholas J. Wareham, Albertine J. Oldehinkel, Lyle J. Palmer, Sarah S. Murray, Peter P. Pramstaller, Stefania Bandinelli, Joachim Heinrich, Erik Ingelsson, Ian J. Deary, Reedik Mägi, Liesbeth Vandenput, Pim van der Harst, Karl C. Desch, Jaspal S. Kooner, Claes Ohlsson, Caroline Hayward, Terho Lehtimäki, Alan R. Shuldiner, Donna K. Arnett, Lawrence J. Beilin, Antonietta Robino, Philippe Froguel, Mario Pirastu, Tine Jess, Wolfgang Koenig, Ruth J.F. Loos, Denis A. Evans, Helena Schmidt, George Davey Smith, P. Eline Slagboom, Gudny Eiriksdottir, Andrew P. Morris, Bruce M. Psaty, Russell P. Tracy, Ilja M. Nolte, Eric Boerwinkle, Sophie Visvikis-Siest, Alex P. Reiner, Myron Gross, Joshua C. Bis, Lude Franke, Oscar H. Franco, Emelia J. Benjamin, Daniel I. Chasman, Josée Dupuis, Harold Snieder, Abbas Dehghan, Behrooz Z. Alizadeh, H. Marike Boezen, Gerjan Navis, Marianne Rots, Morris Swertz, Bruce H.R. Wolffenbuttel, Cisca Wijmenga, Emelia Benjamin, Tarunveer Singh Ahluwalia, James Meigs, Russell Tracy, Josh Bis, Nathan Pankratz, Alex Rainer, James G. Wilson, Josee Dupuis, Bram Prins, Urmo Vaso, Maria Stathopoulou, Terho Lehtimaki, Yalda Jamshidi, Sophie Siest, Andre G. Uitterlinden, Mohammadreza Abdollahi, Renate Schnabel, Ursula M. Schick, Aldi Kraja, Yi-Hsiang Hsu, Daniel S. Tylee, Alyson Zwicker, Rudolf Uher, George Davey-Smith, Andrew Hicks, Cornelia M. van Duijn, Cavin Ward-Caviness, J. Rotter, Ken Rice, Leslie Lange, Eco de Geus, Kari Matti Makela, David Stacey, Johan Eriksson, Tim M. Frayling, Eline P. Slagboom, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University Medical Center Groningen [Groningen] (UMCG), University of Isfahan, University of Tartu, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The University of Texas Health Science Center at Houston (UTHealth), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Split, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Process & Energy Laboratory, Delft University of Technology (TU Delft), Grand Lyon : communauté urbaine de Lyon, Interuniversity Cardiology Institute Netherlands, Department of Twin Research and Genetic Epidemiology, King's College London, London, Huazhong University of Science and Technology [Wuhan] (HUST), Division of Statistical Genomics, Washington University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Institut fuer Theoretische Physik (Institut fuer Theoretische Physik), Universität Heidelberg [Heidelberg] = Heidelberg University, Molecular Epidemiology, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Mahidol University [Bangkok], Northwest A and F University, Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biophysics, CNR, Naples, Università degli studi di Verona = University of Verona (UNIVR), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], University of Maryland School of Medicine, University of Maryland System, Institut National de l'Environnement Industriel et des Risques (INERIS), Institute of Pop. Genetics, CNR, Sassari, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, IT University of Copenhagen (ITU), Robertson Centre for Biostatistics, University of Glasgow, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, King‘s College London, Jinan University [Guangzhou], Institute of Oceanology [China], School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Shardna life science Pula Cagliari, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Medstar Research Institute, Department of Cardiology, Ernst-Moritz-Arndt University, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Department of Internal Medicine, University of Groningen and University Medical Center Groningen, Department of Epidemiology, Harvard School of Public Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Metacohorts Consortium, INEOS Technologies (SWITZERLAND), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, University of Edinburgh, School of Population Health [Crawley, Western Australia], The University of Western Australia (UWA), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), The Scripps Translational Science Institute and Scripps Health, Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, Centre for Population Health Sciences, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Luleå University of Technology (LUT), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Austrian Institute of Technology [Vienna] (AIT), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), Department of Rheumatology and Clinical Epidemiology [Leiden University Medical Center] (LUMC), Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden-Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Virginia, Tampere University Hospital, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Department of Pathological Biochemistry, Royal Infirmary, Oxford University, University of Oxford, University of Newcastle [Callaghan, Australia] (UoN), Department of neurology, Institute of Metabolic Science, MRC, The Wellcome Trust Centre for Human Genetics [Oxford], Uppsala Universitet [Uppsala], QIMR Berghofer Medical Research Institute, Institute of Genetic Epidemiology [Neuherberg, Germany], Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Schizophrenia Research Institute [Sydney], Department of Genetics, University of North Carolina System (UNC)-University of North Carolina System (UNC), Vrije Universiteit Brussel (VUB), Population Health Sciences and Education, St George's University of London, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Health Sciences and Biocenter Oulu, University of Oulu, Medizinische Klinik und Poliklinik, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institute of Clinical Chemistry and Laboratory Medicine, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Departments of Epidemiology and Nutrition, Institute of Epidemiology [Neuherberg] (EPI), Medical University Graz, Transplantation Laboratory [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], CLinical Psychology, Genetics and Pathology, Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Center For Narcolepsy, Stanford University, Centre for Bone and Arthritis Research, University of Gothenburg (GU)-Institute of Medicine, MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh, University of Maryland School of Medicine [Baltimore, MD, USA], Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Stockholm], Stockholm University, University of Bristol [Bristol], Universiteit Leiden, Department of Epidemiology, University of Washington, University of Washington [Seattle], Department of Epidemiology [Rotterdam], University of Groningen [Groningen], Dutch Initiative on Crohn and Colitis (ICC), Icelandic Heart Association [Kopavogur, Iceland] (IHA), Department of Physiology and Biophysics [Jackson, MS, USA], University of Southern Mississippi (USM), Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Department of Social Medicine, School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Medicine [Aurora, CO, USA], University of Colorado [Denver], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Mathematical Institute [Oxford] (MI), Institute of Psychiatry, Psychology & Neuroscience, King's College London, LifeLines Cohort Study, CHARGE Inflammation Working Group, Ligthart, S., Vaez, A., Vosa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., Van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., Wu, Y., Karlsson, R., Barbalic, M., Lin, H., Pool, R., Zhu, G., Mace, A., Sidore, C., Trompet, S., Mangino, M., Sabater-Lleal, M., Kemp, J. P., Abbasi, A., Kacprowski, T., Verweij, N., Smith, A. V., Huang, T., Marzi, C., Feitosa, M. F., Lohman, K. K., Kleber, M. E., Milaneschi, Y., Mueller, C., Huq, M., Vlachopoulou, E., Lyytikainen, L. -P., Oldmeadow, C., Deelen, J., Perola, M., Zhao, J. H., Feenstra, B., Alizadeh, B. Z., Boezen, H. M., Franke, L., van der Harst, P., Navis, G., Rots, M., Snieder, H., Swertz, M., Wolffenbuttel, B. H. R., Wijmenga, C., Amini, M., Benjamin, E., Chasman, D. I., Dehghan, A., Ahluwalia, T. S., Meigs, J., Tracy, R., Bis, J., Eiriksdottir, G., Pankratz, N., Gross, M., Rainer, A., Wilson, J. G., Psaty, B. M., Dupuis, J., Prins, B., Vaso, U., Stathopoulou, M., Lehtimaki, T., Koenig, W., Jamshidi, Y., Siest, S., Uitterlinden, A. G., Abdollahi, M., Schnabel, R., Schick, U. M., Nolte, I. M., Kraja, A., Hsu, Y. -H., Tylee, D. S., Zwicker, A., Uher, R., Davey-Smith, G., Morrison, A. C., Hicks, A., van Duijn, C. M., Ward-Caviness, C., Boerwinkle, E., Rotter, J., Rice, K., Lange, L., de Geus, E., Morris, A. P., Makela, K. M., Stacey, D., Eriksson, J., Frayling, T. M., Slagboom, E. P., Lahti, J., Schraut, K. E., Fornage, M., Suktitipat, B., Chen, W. -M., Li, X., Nutile, T., Malerba, G., Luan, J., Bak, T., Schork, N., Del Greco, M. F., Thiering, E., Mahajan, A., Marioni, R. E., Mihailov, E., Ozel, A. B., Zhang, W., Nethander, M., Cheng, Y. -C., Aslibekyan, S., Ang, W., Gandin, I., Yengo, L., Portas, L., Kooperberg, C., Hofer, E., Rajan, K. B., Schurmann, C., den Hollander, W., Zhao, J., Draisma, H. H. M., Ford, I., Timpson, N., Teumer, A., Huang, H., Wahl, S., Liu, Y., Huang, J., Uh, H. -W., Geller, F., Joshi, P. K., Yanek, L. R., Trabetti, E., Lehne, B., Vozzi, D., Verbanck, M., Biino, G., Saba, Y., Meulenbelt, I., O'Connell, J. R., Laakso, M., Giulianini, F., Magnusson, P. K. E., Ballantyne, C. M., Hottenga, J. J., Montgomery, G. W., Rivadineira, F., Rueedi, R., Steri, M., Herzig, K. -H., Stott, D. J., Menni, C., Franberg, M., S, t. Pourcain B., Felix, S. B., Pers, T. H., Bakker, S. J. L., Kraft, P., Peters, A., Vaidya, D., Delgado, G., Smit, J. H., Grossmann, V., Sinisalo, J., Seppala, I., Williams, S. R., Holliday, E. G., Moed, M., Langenberg, C., Raikkonen, K., Ding, J., Campbell, H., Sale, M. M., Chen, Y. -D. I., James, A. L., Ruggiero, D., Soranzo, N., Hartman, C. A., Smith, E. N., Berenson, G. S., Fuchsberger, C., Hernandez, D., Tiesler, C. M. T., Giedraitis, V., Liewald, D., Fischer, K., Mellstrom, D., Larsson, A., Wang, Y., Scott, W. R., Lorentzon, M., Beilby, J., Ryan, K. A., Pennell, C. E., Vuckovic, D., Balkau, B., Concas, M. P., Schmidt, R., Mendes de Leon, C. F., Bottinger, E. P., Kloppenburg, M., Paternoster, L., Boehnke, M., Musk, A. W., Willemsen, G., Evans, D. M., Madden, P. A. F., Kahonen, M., Kutalik, Z., Zoledziewska, M., Karhunen, V., Kritchevsky, S. B., Sattar, N., Lachance, G., Clarke, R., Harris, T. B., Raitakari, O. T., Attia, J. R., van Heemst, D., Kajantie, E., Sorice, R., Gambaro, G., Scott, R. A., Hicks, A. A., Ferrucci, L., Standl, M., Lindgren, C. M., Starr, J. M., Karlsson, M., Lind, L., Li, J. Z., Chambers, J. C., Mori, T. A., de Geus, E. J. C. N., Heath, A. C., Martin, N. G., Auvinen, J., Buckley, B. M., de Craen, A. J. M., Waldenberger, M., Strauch, K., Meitinger, T., Scott, R. J., Mcevoy, M., Beekman, M., Bombieri, C., Ridker, P. M., Mohlke, K. L., Pedersen, N. L., Boomsma, D. I., Whitfield, J. B., Strachan, D. P., Hofman, A., Vollenweider, P., Cucca, F., Jarvelin, M. -R., Jukema, J. W., Spector, T. D., Hamsten, A., Zeller, T., Nauck, M., Gudnason, V., Qi, L., Grallert, H., Borecki, I. B., Rotter, J. I., Marz, W., Wild, P. S., Lokki, M. -L., Boyle, M., Salomaa, V., Melbye, M., Eriksson, J. G., Wilson, J. F., Penninx, B. W. J. H., Becker, D. M., Worrall, B. B., Gibson, G., Krauss, R. M., Ciullo, M., Zaza, G., Wareham, N. J., Oldehinkel, A. J., Palmer, L. J., Murray, S. S., Pramstaller, P. P., Bandinelli, S., Heinrich, J., Ingelsson, E., Deary, I. J., Magi, R., Vandenput, L., Desch, K. C., Kooner, J. S., Ohlsson, C., Hayward, C., Shuldiner, A. R., Arnett, D. K., Beilin, L. J., Robino, A., Froguel, P., Pirastu, M., Jess, T., Loos, R. J. F., Evans, D. A., Schmidt, H., Slagboom, P. E., Tracy, R. P., Visvikis-Siest, S., Reiner, A. P., Bis, J. C., Franco, O. H., Benjamin, E. J., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Epidemiology, Internal Medicine, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), VU University medical center, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Universität Heidelberg [Heidelberg], University of Verona (UNIVR), Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IT University of Copenhagen, Technical University of Denmark [Lyngby] (DTU), Consiglio Nazionale delle Ricerche (CNR), University of Virginia [Charlottesville], Université de Lausanne (UNIL), University of Oxford [Oxford], University of Newcastle [Australia] (UoN), Centre d'économie industrielle i3 (CERNA i3), Centre National de la Recherche Scientifique (CNRS)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Helmholtz-Zentrum München (HZM), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Universitätsmedizin der Johannes-Gutenberg Universität Mainz, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Cardiff University-Medical Research Council, University of California-University of California, and DE CARVALHO, Philippe
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0301 basic medicine ,Male ,Netherlands Twin Register (NTR) ,Bipolar Disorder ,LD SCORE REGRESSION ,[SDV]Life Sciences [q-bio] ,Genome-wide association study ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Body Mass Index ,inflammatory disorder ,80 and over ,WIDE ASSOCIATION ,EPIDEMIOLOGY ,ta318 ,International HapMap Project ,Child ,Genetics (clinical) ,2. Zero hunger ,Genetics ,Genetics & Heredity ,Aged, 80 and over ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,C-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biology ,system biology ,DEPICT ,Mendelian Randomization Analysis ,11 Medical And Health Sciences ,Middle Aged ,C-reactive protein ,coronary artery disease ,genome-wide association study ,inflammation ,inflammatory disorders ,Mendelian randomization ,schizophrenia ,Adolescent ,Adult ,Aged ,Biomarkers ,C-Reactive Protein ,Female ,Genetic Loci ,Genome-Wide Association Study ,Humans ,Inflammation ,Liver ,Metabolic Networks and Pathways ,Schizophrenia ,Young Adult ,3. Good health ,[SDV] Life Sciences [q-bio] ,Medical genetics ,Biomarker (medicine) ,Life Sciences & Biomedicine ,Human ,medicine.medical_specialty ,CHARGE Inflammation Working Group ,Biology ,IMMUNITY ,ta3111 ,Article ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,medicine ,CORONARY-HEART-DISEASE ,Mendelian Randomization Analysi ,1000 Genomes Project ,METAANALYSIS ,Genetic association ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Science & Technology ,ta1184 ,Metabolic Networks and Pathway ,Biomarker ,INSTRUMENTS ,06 Biological Sciences ,030104 developmental biology ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,LifeLines Cohort Study - Abstract
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
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- 2018
16. Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age
- Author
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Doris Lechner, Miriam Capri, Stefan Böhringer, Stefan Schreiber, Gonneke Willemsen, Paolo Garagnani, Irene Maeve Rea, Andres Metspalu, Palmi V. Jonsson, Thomas B. L. Kirkwood, Lene Christiansen, Fernando Rivadeneira, Giuseppina Rose, J. Wouter Jukema, Serena Dato, Owen A. Ross, Almut Nebel, Cornelia M. van Duijn, Gary Saunders, Bernard Jeune, David J. Stott, Jeanine J. Houwing-Duistermaat, A. Murphy, Anton J. M. de Craen, Friederike Flachsbart, Karen Andersen-Ranberg, Albert Hofman, Ian Ford, Ellen A. Nohr, Giuseppe Passarino, Krista Fischer, Elisa Cevenini, Carmen Martin-Ruiz, Jutta Gampe, Iris Postmus, Christopher P. Nelson, Stefano Salvioli, Alberto Montesanto, Mark Lathrop, Marianne Nygaard, Marie E. Breen, Jennifer Harrow, Hae-Won Uh, Erik B. van den Akker, Thorkild I. A. Sørensen, André G. Uitterlinden, Alexander Viktorin, Bastiaan T. Heijmans, Susan E. McNerlan, Quinta Helmer, Naveed Sattar, Claudio Franceschi, Eco J. C. de Geus, E. Mihailov, Jouke-Jan Hottenga, Qihua Tan, Kari Stefansson, Yoichiro Kamatani, Paolina Crocco, Henning Tiemeier, Stella Trompet, Patrik K. E. Magnusson, Marian Beekman, Riin Tamm, Amke Caliebe, Maris Alver, Femke-Anouska Heinsen, Pilar Galan, Daníel F. Guðbjartsson, Joris Deelen, Linda Broer, Ruud van der Breggen, Kristin L. Ayers, Anna M. Bennet, Dorret I. Boomsma, P. Eline Slagboom, Kaare Christensen, Diana van Heemst, Joanna Collerton, Karen Davies, Rudi G. J. Westendorp, Hélène Blanché, Lavinia Paternoster, Nilesh J. Samani, Hreinn Stefansson, Simon P. Mooijaart, Heather J. Cordell, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), LeidenUniversity Medical Centre, Department of Epidemiology, The Netherlands Cancer Institute, Institute of Genetic Medicine, Newcastle University [Newcastle], National Institute of Public Health, University of Southern Denmark (SDU), Department of Clinical Genetics, Odense University Hospital, Fondation Jean Dausset - Centre d’Étude du Polymorphisme Humain, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Tartu, Institute of Molecular and Cell Biology, Department of Gerontology and Geriatrics, Leiden University Medical Center (LUMC), deCODE genetics [Reykjavik], Christian-Albrechts University of Kiel, University of Calabria, Delft University of Technology (TU Delft), Department of Cardiovascular Sciences, Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospitals Leicester, Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], School of Medicine, Dentistry and Biomedical Sciences [Belfast], Queen's University [Belfast] (QUB), University of Iowa [Iowa City], DIMES: Department of Experimental, Diagnostic and Specialty Medicine, Bologna University Hospital, Institute for Ageing and Health, University of Glasgow, Max Planck Institute for Demographic Research (MPIDR), Max-Planck-Gesellschaft, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), EMGO Institute for Health and Care Research, VU University Amsterdam Medical Center, Landspitali National University Hospital of Iceland, University of Iceland, McGill University = Université McGill [Montréal, Canada], Genome Quebec Innovation Centre, Institut de Génomique, Belfast Health and Social Care Trust, Estonian Biocentre, Partenaires INRAE, Aarhus University [Aarhus], School of Social and Community Medicine, Erasmus University Rotterdam, Mayo Clinic, BHF Glasgow Cardiovascular Research Centre, University Medical Center Schleswig-Holstein, Institute of Cardiovascular and Medical Sciences, Sophia Children's Hospital, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Augustinus Foundation, Avera Institute for Human Genetics (AIHG), AXA Research Fund, Belfast City Hospital Trust Fund, Biobanking and Biomolecular Resources Research Infrastructure (BBMRI -NL) [184.021.007], Biotechnology and Biological Sciences Research Council (BBSRC), Bristol-Myers Squibb, Center for Inherited Disease Research (CIDR), Centre for Medical Systems Biology (CMSB), CERA Foundation, Commissariat a L'Energie Atomique (CEA)-Centre National de Genotypage (CNG), Danish Agency for Science, Technology and Innovation (DASTI)/The Danish Council for Independent Research (DCIR) [11-107308], Danish National Research Foundation (DNRF), Department of Health and Social Services (Northern Ireland), DFG-Cluster of Excellence 'Inflammation at Interfaces', Dunhill Medical Trust [R124/0509], Egmont Foundation, Estonian Science Foundation [7859], Estonian Government [SF0180142s08], European Research Council (ERC) [230374], European Science Foundation (ESF) [EU/QLRT-2001-01254], European Union [FP5-QLK6-CY-2001-00128, FP6-LIFESCIHEALTH-36894, FP6-LSH M-CT-2004-503270, FP7-HEALTH-2007-B-223004, FP7-HEALTH-F4-2007-201413, FP7-HEALTH-F4-2008-202047, FP7-HEALTH-2009-single-stage-242244, FP7-HEALTH-2010-two-stage-259679], Fondation Caisse d'Epargne Rhone-Alpes Lyon CERAL, Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health (NIMH) [MH081802], GenomEUtwin [EU/QLRT-2001-01254, QLG2-CT-2002-01254], Guy's & St Thomas' NHS Foundation Trust, Health Foundation, Heart and Lung foundation [20070481], Innovation-Oriented Research Program on Genomics (SenterNovem) [IGE05007], Institut National de la Recherche Agronomique (INRA), Institut National de la Sante et de la Recherche Medicale (INSERM), King's College London, Medical Research Council (MRC) [G0500997, G0601333], Ministere de l'Enseignement superieur et de la Recherche (MESR), National Institutes of Health (NIH)/National Institute of Aging (NIA) [P01AG08761, R01D0042157-01A, U01DK066134], National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre, NBIC BioAssist [NWO-NBIC/BioAssist/RK/2008.024], Netherlands Consortium for Healthy Ageing (NCHA) [050-060-810], Netherlands Genomics Initiative (NGI), Netherlands Heart Foundation (NHF) [2001 D 032], Netherlands Organization for Scientific Research (NWO, MagW/ZonMW) [904-61-090, 904-61-193, 480-04-004, 400-05-717, Spinozapremie 56-464-14192, 175.010.2005.011, 911-03-012, 985-10-002, Addiction-31160008, Middelg-root-911-09-032], Netspar - Living longer for a good health, NHS North of Tyne (Newcastle Primary Care Trust), Pharmacy Foundation, Regione Autonoma della Sardegna, Rutgers University Cell and DNA Repository [NIMH U24 MH068457-06], Swedish Research Council [M-2005-1112], Tampere University Hospital and Academy of Finland, Danish Interdisciplinary Research Council, Health Foundation (Helsefonden), Ministry for Higher Education, National Program for Research Infrastructure [09-063256], March of Dimes Birth Defects Foundation, Swedish Foundation for Strategic Research (SSF), Unilever Discover Colworth, Universite Paris 13, University of Tartu [SP1GVAR-ENG], Velux Foundation, VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA), Wellcome Trust [084762, 085475, 087436], IDEAL [FP7-HEALTH-2010-two-stage-259679], Research and Education into Ageing-0153, European Regional Development Fund, Deelen J, Beekman M, Uh HW, Broer L, Ayers KL, Tan Q, Kamatani Y, Bennet AM, Tamm R, Trompet S, Guðbjartsson DF, Flachsbart F, Rose G, Viktorin A, Fischer K, Nygaard M, Cordell HJ, Crocco P, van den Akker EB, Böhringer S, Helmer Q, Nelson CP, Saunders GI, Alver M, Andersen-Ranberg K, Breen ME, van der Breggen R, Caliebe A, Capri M, Cevenini E, Collerton JC, Dato S, Davies K, Ford I, Gampe J, Garagnani P, de Geus EJ, Harrow J, van Heemst D, Heijmans BT, Heinsen FA, Hottenga JJ, Hofman A, Jeune B, Jonsson PV, Lathrop M, Lechner D, Martin-Ruiz C, McNerlan SE, Mihailov E, Montesanto A, Mooijaart SP, Murphy A, Nohr EA, Paternoster L, Postmus I, Rivadeneira F, Ross OA, Salvioli S, Sattar N, Schreiber S, Stefánsson H, Stott DJ, Tiemeier H, Uitterlinden AG, Westendorp RG, Willemsen G, Samani NJ, Galan P, Sørensen TI, Boomsma DI, Jukema JW, Rea IM, Passarino G, de Craen AJ, Christensen K, Nebel A, Stefánsson K, Metspalu A, Magnusson P, Blanché H, Christiansen L, Kirkwood TB, van Duijn CM, Franceschi C, Houwing-Duistermaat JJ, Slagboom PE., Leiden Univ, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands [ 2 ] Leiden Univ, Netherlands Consortium Healthy Ageing, NL-2300 RC Leiden, Netherlands [ 3 ] Leiden Univ, Dept Med Stat & Bioinformat, NL-2300 RC Leiden, Netherlands [ 4 ] Leiden Univ, Dept Cardiol, NL-2300 RC Leiden, Netherlands [ 5 ] Leiden Univ, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands [ 6 ] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands [ 7 ] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands [ 8 ] Newcastle Univ, Int Ctr Life, Inst Med Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England [ 9 ] Univ So Denmark, Inst Publ Hlth, DK-5000 Odense C, Denmark [ 10 ] Univ So Denmark, Inst Clin Res, Dept Gynecol & Obstet, DK-5000 Odense C, Denmark [ 11 ] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark [ 12 ] Odense Univ Hosp, Clin Biochem & Pharmacol, DK-5000 Odense C, Denmark [ 13 ] Fdn Jean Dausset CEPH, F-75010 Paris, France [ 14 ] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden [ 15 ] Univ Tartu, Estonian Genome Ctr, Tartu 51010, Estonia [ 16 ] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia [ 17 ] deCODE Genet, Populat Gen, IS-101 Reykjavik, Iceland [ 18 ] Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany [ 19 ] Univ Kiel, Inst Med Informat & Stat, D-24105 Kiel, Germany [ 20 ] Univ Calabria, Dept Biol Ecol & Earth Sci, I-87036 Arcavacata Di Rende, Italy [ 21 ] Delft Univ Technol, Delft Bioinformat Lab, NL-2600 GA Delft, Netherlands [ 22 ] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England [ 23 ] Glenfield Hosp, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester LE3 9QP, Leics, England [ 24 ] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England [ 25 ] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Belfast BT9 7BL, Antrim, North Ireland [ 26 ] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA [ 27 ] Univ Bologna, Dept Expt Diagnost & Specialty Med, I-40126 Bologna, Italy [ 28 ] Univ Bologna, Interdepartmental Ctr L Galvani, I-40126 Bologna, Italy [ 29 ] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 5PL, Tyne & Wear, England [ 30 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow G12 8QQ, Lanark, Scotland [ 31 ] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8QQ, Lanark, Scotland [ 32 ] Max Planck Inst Demograf Forsch, Lab Stat Demog, D-18057 Rostock, Germany [ 33 ] Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands [ 34 ] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, NL-1081 BT Amsterdam, Netherlands [ 35 ] Landspitali Univ Hosp, IS-101 Reykjavik, Iceland [ 36 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland [ 37 ] CEA, Inst Genom, F-91057 Evry, France [ 38 ] McGill Univ, Montreal, PQ H3G 1A4, Canada [ 39 ] Genome Quebec Innovat Ctr, Montreal, PQ H3G 1A4, Canada [ 40 ] Belfast Hlth & Social Care Trust, Cytogenet Lab, Belfast BT8 8BH, Antrim, North Ireland [ 41 ] Estonian Bioctr, EE-51010 Tartu, Estonia [ 42 ] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark [ 43 ] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol BS8 2BN, Avon, England [ 44 ] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA [ 45 ] Univ Glasgow, Fac Med, BHF Glasgow Cardiovasc Res Ctr, Glasgow G12 8TA, Lanark, Scotland [ 46 ] Univ Kiel, PopGen Biobank, D-24105 Kiel, Germany [ 47 ] Univ Hosp Schleswig Holstein, D-24105 Kiel, Germany [ 48 ] Sophia Childrens Univ Hosp, Erasmus Med Ctr, Dept Child & Adolescent Psychiat, NL-3000 CA Rotterdam, Netherlands [ 49 ] Univ Paris 04, UREN, U557, INSERM, F-93017 Bobigny, France [ 50 ] U1125 Inra, F-93017 Bobigny, France [ 51 ] Cnam, F-93017 Bobigny, France [ 52 ] Univ Paris 13, CRNH IdF, F-93017 Bobigny, France [ 53 ] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr, DK-2200 Copenhagen N, Denmark [ 54 ] Inst Prevent Med, DK-2000 Copenhagen, Denmark [ 55 ] Frederiksberg Univ Hosp, DK-2000 Copenhagen, Denmark [ 56 ] Interuniv Cardiol Inst Netherlands, NL-3501 DG Utrecht, Netherlands [ 57 ] Bellaria Hosp, IRCCS Inst Neurol Sci, I-40139 Bologna, Italy [ 58 ] CNR, ISOF, I-40129 Bologna, Italy, Epidemiology, Surgery, Internal Medicine, Child and Adolescent Psychiatry / Psychology, ProdInra, Migration, Vrije Universiteit Amsterdam [Amsterdam] (VU), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), VU University Amsterdam, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes
- Subjects
Male ,Netherlands Twin Register (NTR) ,Disease/genetics ,Lífslíkur ,Longevity/genetics ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Genetic Linkage ,Genome-wide association study ,0302 clinical medicine ,Prospective Studies ,Genetics (clinical) ,Genetics ,Aged, 80 and over ,0303 health sciences ,education.field_of_study ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Association Studies Articles ,Age Factors ,Chromosome Mapping ,Genetic Loci/physiology ,General Medicine ,3. Good health ,Europe ,Phenotype ,Cardiovascular Diseases ,Hypertension ,Chromosomes, Human, Pair 5 ,Female ,Human Longevity, genetics, meta-analysis ,Aging/genetics ,Cardiology and Cardiovascular Medicine ,HUMAN AGING ,Longevity ,European Continental Ancestry Group ,Population ,HUMAN GENETICS ,Single-nucleotide polymorphism ,Locus (genetics) ,Biology ,FAMILIAL LONGEVITY ,White People ,03 medical and health sciences ,Gene mapping ,SDG 3 - Good Health and Well-being ,Cardiovascular Diseases/genetics ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,Allele ,education ,Molecular Biology ,Aged ,030304 developmental biology ,Genetic association ,Öldrun ,Genome, Human ,Arfgengi ,Minor allele frequency ,Ageing ,Genetic Loci ,Chromosomes, Human, Pair 19 ,Hypertension/genetics ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Genome-Wide Association Study - Abstract
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. The genetic contribution to the variation in human lifespan is ∼ 25%. Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality. We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16 121 younger controls (
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- 2014
17. Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals
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Seppo Koskinen, Christian Herder, Daniel I. Chasman, Andrew R. Wood, Jonna L. Grimsby, J.F. Wilson, Day Inm., Massimo Mangino, Gonneke Willemsen, Robert W. Mahley, Cristian Pattaro, Nicole L. Glazer, T.B. Harris, Irene Pichler, M S Sandhu, D. van Heemst, Christine Proença, Martha Ganser, Robert A. Hegele, Richa Saxena, Eleftheria Zeggini, Markku Laakso, Peter Kraft, Judith B. Borja, Karen L. Mohlke, J B Richards, de Geus Ejc., Robert Sladek, Cristen J. Willer, Samy Hadjadj, S.M. Boekholdt, Gina M. Peloso, Kijoung Song, Sutapa Mukherjee, Gudmar Thorleifsson, Winston Hide, Mark I. McCarthy, Ruth E. Pakyz, Marian Beekman, Ayellet V. Segrè, Inga Prokopenko, Ping An, George Dedoussis, Danielle Posthuma, Jeanette Erdmann, Simon J. Griffin, Nilesh J. Samani, Inke R. König, Frank B. Hu, Lokki M-L., David M. Evans, Xiaohui Li, Valgerdur Steinthorsdottir, Aimo Ruokonen, A Pouta, Kerrin S. Small, Cecilia M. Lindgren, O Le Bacquer, Xijing Han, Florian Kronenberg, E Katsareli, Christian Dina, S. Gabriel, Jochen Spranger, James S. Pankow, M. Kloppenburg, Penninx Bwjh., Torben Hansen, Josh Smith, Jennie Hui, Gordon H. Williams, Mark Seielstad, Ingrid B. Borecki, Weihua Zhang, Peter P. Pramstaller, Stephen J. Sharp, Neil R. Robertson, Zee Ryl., Mike Sampson, Angela Silveira, C.M. van Duijn, Anders Hamsten, Peter Shrader, Denis Rybin, Chen Y-Di., Gunnar Sigurdsson, Michael Stumvoll, Russel Tracy, Mark O. Goodarzi, Göran Hallmans, Michael R. Erdos, Valeriya Lyssenko, Juha Saharinen, Sven Bergmann, Jeffrey R. O'Connell, Debbie A Lawlor, Thomas Meitinger, Yvonne Böttcher, Jérôme Delplanque, Sarah G. Buxbaum, Silvia Naitza, Shah Ebrahim, Graham A. Hitman, Angelo Scuteri, Aroon D. Hingorani, Heribert Schunkert, François Pattou, Claudia Lamina, A L Elliott, Sekar Kathiresan, Dawn M. Waterworth, Jennifer A. Brody, Thomas Quertermous, Leena Peltonen, Josephine M. Egan, Daniel J. Rader, J F Peden, Yarnell Jwg., Daniel S. 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Havulinna, Toby Johnson, Samuli Ripatti, Erik Ingelsson, Mario A. Morken, Carl G. P. Platou, Anke Tönjes, Qi Sun, Narisu Narisu, S J Bumpstead, Jose M. Ordovas, Alan B. Feranil, L Groop, P Chines, Sara M. Willems, Perry Jrb., Matthew A. Allison, Jan Scott, Cécile Lecoeur, Kastelein Jjp., Herman A. Taylor, Anyuan Cao, Christopher J. Groves, Lincoln D. Stein, Laura J. Scott, John Beilby, Kristin G. Ardlie, Christopher S. Franklin, Yoav Ben-Shlomo, B M Shields, N J Timpson, Marco Orrù, Amélie Bonnefond, Kiran Musunuru, Murielle Bochud, Udo Seedorf, Yongmei Liu, Guillaume Lettre, Lee J-Y., Alan R. Shuldiner, Ryan P. Welch, David J. Hunter, John Whitfield, Klaus Strassburger, Khaw K-T., Hartikainen A-L., Gunnar Sigurðsson, Lu Qi, Richard N. Bergman, G M Lathrop, Sigrid W. Fouchier, T van Herpt, David S. Siscovick, Igor Rudan, Richard M. Watanabe, Themistocles L. Assimes, Nicholas G. Martin, Ozren Polasek, Dhiraj Varma, K Kim, Oliver Hofmann, Nicholas D. Hastie, S Bumpstead, Jose C. 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Voight, Wolfgang Rathmann, Mark Walker, Markus Perola, M. A. Province, Veikko Salomaa, James B. Meigs, George Davey Smith, Robert Clarke, Gerard Waeber, Stefania Bandinelli, Sally L. Ricketts, Kaisa Silander, Loos Rjf., Amanda J. Bennett, John C. Chambers, Marilyn C. Cornelis, L A Cupples, Andrew T. Hattersley, M Sandhu, Marju Orho-Melander, C M van Duijn, Olli T. Raitakari, David Meyre, Ida Surakka, Jouke-Jan Hottenga, Uh H-W., Kari Stefansson, David Melzer, P E Slagboom, Kristian Midthjell, Robert K. Semple, James P. Pirruccello, Aloysius G Lieverse, Åsa Johansson, Michael Roden, Felicity Payne, Eric J.G. Sijbrands, N P Burtt, David R. Hillman, Michael Marmot, Todd Green, Eric E. Schadt, Sijbrands Ejg., Tien Yin Wong, Coin Ljm., K B Boström, Olov Rolandsson, A D Morris, David Altshuler, Harald Grallert, L C Groop, Alan F. Wright, Karen Kapur, Xueling Sim, Philippe Froguel, K O Kyvik, T. Lauritzen, Linda S. 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Kloppenburg, M, Adair, L, Borja, Jb, DIAGRAM+, Consortium, Magic, Consortium, Glgc, Investigator, Muther, Consortium, Wilson, Jg, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, Tm, Allison, Ma, Redline, S, Buxbaum, Sg, Mohlke, Kl, Meulenbelt, I, Ballantyne, Cm, Dedoussis, Gv, Hu, Fb, Liu, Y, Paulweber, B, Spector, Td, Slagboom, Pe, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, Jc, Salomaa, V, Eriksson, Jg, Frayling, Tm, Hicks, Aa, Lehtimäki, T, Smith, Gd, Siscovick, D, Kronenberg, F, van Duijn, C, Loos, Rj, Waterworth, Dm, Meigs, Jb, Dupuis, J, Richards, Jb, Voight, Bf, Scott, Lj, Steinthorsdottir, V, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, 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Hveem, K, Laakso, M, Morris, Ad, Palmer, Cn, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Pedersen, O, Barroso, I, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Altshuler, D, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Elliott, P, Rybin, D, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Lajunen, T, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Diagram, Consortium, Giant, Consortium, Global B., Pgen Consortium, Borecki, Ib, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Serrano Ríos, M, Lind, L, Palmer, Lj, Hu FB, 1st, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Procardis, Consortium, Buchanan, Ta, Valle, Tt, Rotter, Ji, Penninx, Bw, Boomsma, Di, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Peltonen, L, Mooser, V, Magic, Investigator, Glgc, Consortium, Musunuru, K, Smith, Av, Edmondson, Ac, Stylianou, Im, Koseki, M, Pirruccello, Jp, Chasman, Di, Johansen, Ct, Fouchier, Sw, Peloso, Gm, Barbalic, M, Ricketts, Sl, Bis, Jc, Feitosa, Mf, Orho Melander, M, Melander, O, Li, X, Cho, Y, Go, Mj, Kim, Yj, Lee, Jy, Park, T, Kim, K, Sim, X, Ong, Rt, Croteau Chonka, Dc, Lange, La, Smith, Jd, Ziegler, A, Zhang, W, Zee, Ry, Whitfield, Jb, Thompson, Jr, Surakka, I, Smit, Jh, Sinisalo, J, Scott, J, Saharinen, J, Sabatti, C, Rose, Lm, Roberts, R, Rieder, M, Parker, An, Pare, G, O'Donnell, Cj, Nieminen, M, Nickerson, Da, Montgomery, Gw, Mcardle, W, Masson, D, Martin, Ng, Marroni, F, Lucas, G, Luben, R, Lokki, Ml, Lettre, G, Launer, Lj, Lakatta, Eg, Laaksonen, R, König, Ir, Khaw, Kt, Kaplan, Lm, Johansson, Å, Janssens, Ac, Igl, W, Hovingh, Gk, Hengstenberg, C, Havulinna, A, Hastie, Nd, Harris, Tb, Haritunians, T, Hall, A, Groop, Lc, Gonzalez, E, Freimer, Nb, Erdmann, J, Ejebe, Kg, Döring, A, Dominiczak, Af, Demissie, S, de Faire, U, Caulfield, Mj, Boekholdt, Sm, Assimes, Tl, Quertermous, T, Seielstad, M, Wong, Ty, Tai, E, Feranil, Ab, Kuzawa, Cw, Taylor HA, Jr, Gabriel, Sb, Holm, H, Gudnason, V, Krauss, Rm, Ordovas, Jm, Munroe, Pb, Tall, Ar, Hegele, Ra, Kastelein, Jj, Schadt, Ee, Strachan, Dp, Reilly, Mp, Samani, Nj, Schunkert, H, Cupples, La, Ridker, Pm, Rader, Dj, Kathiresan, S., Medical Research Council (MRC), Perry, John [0000-0001-6483-3771], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Semple, Robert [0000-0001-6539-3069], Griffin, Simon [0000-0002-2157-4797], Barroso, Ines [0000-0001-5800-4520], Soranzo, Nicole [0000-0003-1095-3852], Wheeler, Eleanor [0000-0002-8616-6444], Luan, Jian'an [0000-0003-3137-6337], Forouhi, Nita [0000-0002-5041-248X], Sharp, Stephen [0000-0003-2375-1440], Sovio, Ulla [0000-0002-0799-1105], Zhao, Jing Hua [0000-0003-4930-3582], Luben, Robert [0000-0002-5088-6343], Khaw, Kay-Tee [0000-0002-8802-2903], Sandhu, Manjinder [0000-0002-2725-142X], Apollo - University of Cambridge Repository, Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Lifestyle, Overweight and Diabetes, Other departments, Experimental Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Human genetics, Psychiatry, NCA - Attention & Cognition, EMGO - Lifestyle, overweight and diabetes, Lääketieteen yksikkö - School of Medicine, University of Tampere, Institute for Molecular Medicine Finland, Hjelt Institute (-2014), Clinicum, Department of General Practice and Primary Health Care, Department of Public Health, Haartman Institute (-2014), Transplantation Laboratory, Biostatistics Helsinki, Quantitative Genetics, Complex Disease Genetics, Genetic Epidemiology, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Olson, J., Kronmal, R., Robbins, J., Chaves, PH., Burke, G., Kuller, LH., Tracy, R., Gottdiener, J., Prineas, R., Becker, JT., Enright, P., Klein, R., and O'Leary, DH.
- Subjects
Netherlands Twin Register (NTR) ,Male ,Insulin Resistance/genetics ,VARIANTS ,0302 clinical medicine ,POPULATION ,African Americans ,blood/genetics ,0303 health sciences ,education.field_of_study ,Adiponectin/blood ,Adiponectin/genetics ,Asian Continental Ancestry Group ,Cholesterol, HDL/genetics ,Diabetes Mellitus, Type 2/genetics ,European Continental Ancestry Group ,Female ,Gene Expression ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Glucose Tolerance Test ,Humans ,Metabolic Networks and Pathways ,Polymorphism, Single Nucleotide ,Waist-Hip Ratio ,Global B Pgen Consortium ,MAGIC investigators ,3. Good health ,Cholesterol ,Medicine ,Adiponectin ,Type 2 ,medicine.medical_specialty ,HDL ,Biolääketieteet - Biomedicine ,Single-nucleotide polymorphism ,DIAGRAM Consortium ,White People ,Molecular Genetics ,GLGC Consortium ,03 medical and health sciences ,Asian People ,SDG 3 - Good Health and Well-being ,GIANT Consortium ,Diabetes Mellitus ,Genetics ,DIAGRAM+ Consortium ,GENOME-WIDE ASSOCIATION ,Polymorphism ,education ,Biology ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,0604 Genetics ,Science & Technology ,GLGC Investigators ,nutritional and metabolic diseases ,ta3121 ,medicine.disease ,Obesity ,Black or African American ,blood/genetics, African Americans, Asian Continental Ancestry Group, Cholesterol ,genetics, Diabetes Mellitus ,genetics, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance ,genetics, Male, Metabolic Networks and Pathways, Polymorphism ,Single Nucleotide, Waist-Hip Ratio ,Endocrinology ,Diabetes Mellitus, Type 2 ,Developmental Biology ,Type 2/genetics ,Cancer Research ,Type 2 diabetes ,QH426-470 ,030204 cardiovascular system & hematology ,LIPID CONCENTRATIONS ,GENETICS & HEREDITY ,Genetics (clinical) ,RISK ,2. Zero hunger ,INSULIN-RESISTANCE ,Glucose tolerance test ,medicine.diagnostic_test ,MAGIC Consortium ,Single Nucleotide ,ADIPOSE-TISSUE ,CORONARY-ARTERY-DISEASE ,Life Sciences & Biomedicine ,Research Article ,Clinical Research Design ,GENETIC-BASIS ,Population ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,ddc:610 ,030304 developmental biology ,RECEPTOR ,Cholesterol, HDL ,Human Genetics ,HDL/genetics ,3121 General medicine, internal medicine and other clinical medicine ,MuTHER Consortium ,3111 Biomedicine ,Procardis Consortium ,Insulin Resistance - Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p, Author Summary Serum adiponectin levels are highly heritable and are inversely correlated with the risk of type 2 diabetes (T2D), coronary artery disease, stroke, and several metabolic traits. To identify common genetic variants associated with adiponectin levels and risk of T2D and metabolic traits, we conducted a meta-analysis of genome-wide association studies of 45,891 multi-ethnic individuals. In addition to confirming that variants at the ADIPOQ and CDH13 loci influence adiponectin levels, our analyses revealed that 10 new loci also affecting circulating adiponectin levels. We demonstrated that expression levels of several genes in these candidate regions are associated with serum adiponectin levels. Using a powerful novel method to assess the contribution of the identified variants with other traits using summary-level results from large-scale GWAS consortia, we provide evidence that the risk alleles for adiponectin are associated with deleterious changes in T2D risk and metabolic syndrome traits (triglycerides, HDL, post-prandial glucose, insulin, and waist-to-hip ratio), demonstrating that the identified loci, taken together, impact upon metabolic disease.
- Published
- 2012
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