Author: "Gieger, C." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Gieger, C."' showing total 1,233 results

Start Over Author "Gieger, C."

1,233 results on '"Gieger, C."'

1. Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author: Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, Ong, KK, Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, and Ong, KK
Abstract: Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Published: 2024

2. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author: Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., Medici, M., Sterenborg, R.B.T.M., Steinbrenner, I., Li, Yong, Bujnis, M.N., Naito, T., Marouli, E., Galesloot, T.E., Babajide, O., Andreasen, L., Astrup, A., Åsvold, B.O., Bandinelli, S., Beekman, M., Beilby, J.P., Bork-Jensen, J., Boutin, T., Brody, J.A., Brown, S.J., Brumpton, B., Campbell, P.J., Cappola, A.R., Ceresini, G., Chaker, L., Chasman, D.I., Concas, M.P., Coutinho de Almeida, Rodrigo, Cross, S.M., Cucca, F., Deary, I.J., Kjaergaard, A.D., Echouffo Tcheugui, J.B., Ellervik, C., Eriksson, J.G., Ferrucci, L., Freudenberg, J., Fuchsberger, C., Gieger, C., Giulianini, F., Gögele, M., Graham, S.E., Grarup, N., Gunjača, I., Hansen, T., Harding, B.N., Harris, S.E., Haunsø, S., Hayward, C., Hui, J., Ittermann, T., Jukema, J.W., Kajantie, E., Kanters, J.K., Kårhus, L.L., Kiemeney, L.A.L.M., Kühnel, B., Lahti, J., Langenberg, C., Lapauw, B., Leese, G., Li, Shuo, Liewald, D.C.M., Linneberg, A., Lominchar, J.V.T., Luan, Jian'an, Martin, N.G., Matana, A., Meima, M.E., Meitinger, T., Meulenbelt, I., Mitchell, B.D., Møllehave, L.T., Mora, S., Naitza, S., Nauck, M., Netea-Maier, R.T., Noordam, R., Nursyifa, C., Okada, Y., Onano, S., Papadopoulou, A., Palmer, C.N.A., Pattaro, C., Pedersen, O., Peters, A., Pietzner, M., Polašek, O., Pramstaller, P.P., Psaty, B.M., Punda, A., Ray, D., Redmond, P., Richards, J.B., Ridker, P.M., Russ, T.C., Ryan, K.A., Olesen, M.S., Schultheiss, U.T., Selvin, E., Siddiqui, M.K., Teumer, A., and Medici, M.
Abstract: Contains fulltext : 304858.pdf (Publisher’s version ) (Open Access), To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.
Published: 2024

3. A Fecal Metabolite Signature of Impaired Fasting Glucose: Results From Two Independent Population-Based Cohorts

Author: Nogal, A, Tettamanzi, F, Dong, Q, Louca, P, Visconti, A, Christiansen, C, Breuninger, T, Linseisen, J, Grallert, H, Wawro, N, Asnicar, F, Wong, K, Baleanu, A, Michelotti, G, Segata, N, Falchi, M, Peters, A, Franks, P, Bagnardi, V, Spector, T, Bell, J, Gieger, C, Valdes, A, Menni, C, Nogal A., Tettamanzi F., Dong Q., Louca P., Visconti A., Christiansen C., Breuninger T., Linseisen J., Grallert H., Wawro N., Asnicar F., Wong K., Baleanu A. -F., Michelotti G. A., Segata N., Falchi M., Peters A., Franks P. W., Bagnardi V., Spector T. D., Bell J. T., Gieger C., Valdes A. M., Menni C., Nogal, A, Tettamanzi, F, Dong, Q, Louca, P, Visconti, A, Christiansen, C, Breuninger, T, Linseisen, J, Grallert, H, Wawro, N, Asnicar, F, Wong, K, Baleanu, A, Michelotti, G, Segata, N, Falchi, M, Peters, A, Franks, P, Bagnardi, V, Spector, T, Bell, J, Gieger, C, Valdes, A, Menni, C, Nogal A., Tettamanzi F., Dong Q., Louca P., Visconti A., Christiansen C., Breuninger T., Linseisen J., Grallert H., Wawro N., Asnicar F., Wong K., Baleanu A. -F., Michelotti G. A., Segata N., Falchi M., Peters A., Franks P. W., Bagnardi V., Spector T. D., Bell J. T., Gieger C., Valdes A. M., and Menni C.
Abstract: Prediabetes is a metabolic condition associated with gut mi-crobiome composition, although mechanisms remain elu-sive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicoti-nate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02–5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16–1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97–8], P = 0.0002). Although these are host-produced me-tabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset.
Published: 2023

4. Meta-GWAS identifies FADS2 a novel locus for PCSK9 concentrations

Author: Kheirkhah, A., primary, Schachtl-Rieß, J., additional, Lamina, C., additional, Di Maio, S., additional, Koller, A., additional, Schönherr, S., additional, Coassin, S., additional, Forer, L., additional, Schultheiß, U.T., additional, Sekula, P., additional, Kotsis, F., additional, Gieger, C., additional, Peters, A., additional, Köttgen, A., additional, Eckardt, K.-U., additional, and Kronenberg, F., additional
Published: 2023
Full Text: View/download PDF

5. Methylglyoxal – a central metabolic factor in restless legs syndrome?

Author: Harrer, P., primary, Folberth, J., additional, Zhao, C., additional, Schormair, B., additional, Tilch, E., additional, Gieger, C., additional, Peters, A., additional, Oexle, K., additional, Schwaninger, M., additional, and Winkelmann, J., additional
Published: 2022
Full Text: View/download PDF

6. An epigenome-wide association study meta-analysis of educational attainment

Author: Linnér, R Karlsson, Marioni, R E, Rietveld, C A, Simpkin, A J, Davies, N M, Watanabe, K, Armstrong, N J, Auro, K, Baumbach, C, Bonder, M J, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, McRae, A F, Mandaviya, P R, Seppälä, I, Wang, Y, Baglietto, L, Binder, E B, Harris, S E, Hodge, A M, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, K A, Medland, S E, Metspalu, A, Milani, L, Milne, R L, Pattie, A, Pedersen, N L, Peters, A, Polidoro, S, Räikkönen, K, Severi, G, Starr, J M, Stolk, L, Waldenberger, M, Consortium, B IOS, Eriksson, J G, Esko, T, Franke, L, Gieger, C, Giles, G G, Hägg, S, Jousilahti, P, Kaprio, J, Kähönen, M, Lehtimäki, T, Martin, N G, van Meurs, J BC, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, O T, Sachdev, P S, Taskesen, E, Uitterlinden, A G, Vineis, P, Wijmenga, C, Wright, M J, Relton, C, Smith, G Davey, Deary, I J, Koellinger, P D, and Benjamin, D J
Published: 2017
Full Text: View/download PDF

7. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author: Jaworek, T, Xu, H, Gaynor, BJ, Cole, JW, Rannikmae, K, Stanne, TM, Tomppo, L, Abedi, V, Amouyel, P, Armstrong, ND, Attia, J, Bell, S, Benavente, OR, Boncoraglio, GB, Butterworth, A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez, J, Chen, Z, Chong, M, Cruchaga, C, Cushman, M, Danesh, J, Debette, S, Duggan, DJ, Durda, JP, Engstrom, G, Enzinger, C, Faul, JD, Fecteau, NS, Fernandez-Cadenas, I, Gieger, C, Giese, A-K, Grewal, RP, Grittner, U, Havulinna, AS, Heitsch, L, Hochberg, MC, Holliday, E, Hu, J, Ilinca, A, INVENT Consortium, Irvin, MR, Jackson, RD, Jacob, MA, Janssen, RR, Jimenez-Conde, J, Johnson, JA, Kamatani, Y, Kardia, SL, Koido, M, Kubo, M, Lange, L, Lee, J-M, Lemmens, R, Levi, CR, Li, J, Li, L, Lin, K, Lopez, H, Luke, S, Maguire, J, McArdle, PF, McDonough, CW, Meschia, JF, Metso, T, Muller-Nurasyid, M, O'Connor, TD, O'Donnell, M, Peddareddygari, LR, Pera, J, Perry, JA, Peters, A, Putaala, J, Ray, D, Rexrode, K, Ribases, M, Rosand, J, Rothwell, PM, Rundek, T, Ryan, KA, Sacco, RL, Salomaa, V, Sanchez-Mora, C, Schmidt, R, Sharma, P, Slowik, A, Smith, JA, Smith, NL, Wassertheil-Smoller, S, Soederholm, M, Stine, OC, Strbian, D, Sudlow, CL, Tatlisumak, T, Terao, C, Thijs, V, Torres-Aguila, NP, Tregouet, D-A, Tuladhar, AM, Veldink, JH, Walters, RG, Weir, DR, Woo, D, Worrall, BB, Hong, CC, Ross, O, Zand, R, Leeuw, F-ED, Lindgren, AG, Pare, G, Anderson, CD, Markus, HS, Jern, C, Malik, R, Dichgans, M, Mitchell, BD, Kittner, SJ, and Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)
Subjects: Neurology & Neurosurgery, 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
Abstract: BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). DISCUSSION: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
Published: 2022

8. The effect of the LPA variant P.THR3888PRO on lipoprotein(a) and coronary artery disease is modified by the LPA KIV-2 splice site variant 4925g>A

Author: Grüneis, R., primary, Lamina, C., additional, Di Maio, S., additional, Schönherr, S., additional, Zöscher, P., additional, Forer, L., additional, Peters, A., additional, Gieger, C., additional, Köttgen, A., additional, Kronenberg, F., additional, and Coassin, S., additional
Published: 2022
Full Text: View/download PDF

9. Assessment of the association of exposure to polycyclic aromatic hydrocarbons, oxidative stress, and inflammation: A cross-sectional study in Augsburg, Germany

Author: Wu, Xiao, primary, Cao, Xin, additional, Lintelmann, Jutta, additional, Peters, Annette, additional, Koenig, Wolfgang, additional, Zimmermann, Ralf, additional, Schneider, Alexandra, additional, Wolf, Kathrin, additional, Peters, A., additional, Schwettmann, L., additional, Leidl, R., additional, Heier, M., additional, Linkohr, B., additional, Grallert, H., additional, Gieger, C., additional, and Linseisen, J., additional
Published: 2022
Full Text: View/download PDF

10. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Author: Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., Hoed, Marcel Den, Wang, Zhe, Emmerich, A., Pillon, N.J., Moore, T., Hemerich, D., Cornelis, M.C., Mazzaferro, E., Broos, S., Ahluwalia, T.S., Bartz, T.M., Bentley, A.R., Bielak, L.F., Chong, M., Chu, A.Y., Berry, D., Dorajoo, R., Dueker, N.D., Kasbohm, E., Feenstra, B., Feitosa, M.F., Gieger, C., Graff, M, Hall, L.M., Haller, T., Hartwig, F.P., Hillis, D.A., Huikari, V., Heard-Costa, N., Holzapfel, C., Jackson, A.U., Johansson, Å., Jørgensen, A.M., Kaakinen, M.A., Karlsson, R., Kerr, K.F., Kim, Boram, Koolhaas, C.M., Kutalik, Z., Lagou, V., Lind, P.A., Lorentzon, M., Lyytikäinen, L.P., Mangino, M., Metzendorf, C., Monroe, K.R., Pacolet, A., Pérusse, L., Pool, R., Richmond, R.C., Rivera, N.V., Robiou-du-Pont, S., Schraut, K.E., Schulz, C.A., Stringham, H.M., Tanaka, T., Teumer, A., Turman, C., Most, P.J. van der, Vanmunster, M., Rooij, F.J. van, Vliet-Ostaptchouk, J.V. Van, Zhang, Xiaoshuai, Zhao, J.H., Zhao, W, Balkhiyarova, Z., Balslev-Harder, M.N., Baumeister, S.E., Beilby, J., Blangero, J., Boomsma, D.I., Brage, S., Braund, P.S., Brody, J.A., Bruinenberg, M., Ekelund, U., Liu, C.T., Cole, J.W., Collins, F.S., Cupples, L.A., Esko, T., Enroth, S., Faul, J.D., Fernandez-Rhodes, L., Fohner, A.E., Franco, O.H., Galesloot, T.E., Gordon, S.D.S., Grarup, N., Hartman, C.A., Heiss, G., Hui, J., Illig, T., Jago, R., James, A., Joshi, P.K., Jung, T., Kähönen, M., Kilpeläinen, T.O., Koh, W.P., Kolcic, I., Kiemeney, L.A.L.M., Loos, R.J.F., and Hoed, Marcel Den
Abstract: Contains fulltext : 282313.pdf (Publisher’s version ) (Open Access), Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II(A) muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Published: 2022

11. Uncovering the Contribution of Moderate-Penetrance Susceptibility Genes to Breast Cancer by Whole-Exome Sequencing and Targeted Enrichment Sequencing of Candidate Genes in Women of European Ancestry.

Author: Dumont, M, Weber-Lassalle, N, Joly-Beauparlant, C, Ernst, C, Droit, A, Feng, B-J, Dubois, S, Collin-Deschesnes, A-C, Soucy, P, Vallée, M, Fournier, F, Lemaçon, A, Adank, MA, Allen, J, Altmüller, J, Arnold, N, Ausems, MGEM, Berutti, R, Bolla, MK, Bull, S, Carvalho, S, Cornelissen, S, Dufault, MR, Dunning, AM, Engel, C, Gehrig, A, Geurts-Giele, WRR, Gieger, C, Green, J, Hackmann, K, Helmy, M, Hentschel, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Horváth, J, Ikram, MA, Kaulfuß, S, Keeman, R, Kuang, D, Luccarini, C, Maier, W, Martens, JWM, Niederacher, D, Nürnberg, P, Ott, C-E, Peters, A, Pharoah, PDP, Ramirez, A, Ramser, J, Riedel-Heller, S, Schmidt, G, Shah, M, Scherer, M, Stäbler, A, Strom, TM, Sutter, C, Thiele, H, van Asperen, CJ, van der Kolk, L, van der Luijt, RB, Volk, AE, Wagner, M, Waisfisz, Q, Wang, Q, Wang-Gohrke, S, Weber, BHF, Genome Of The Netherlands Project, Ghs Study Group, Devilee, P, Tavtigian, S, Bader, GD, Meindl, A, Goldgar, DE, Andrulis, IL, Schmutzler, RK, Easton, DF, Schmidt, MK, Hahnen, E, Simard, J, Dumont, M, Weber-Lassalle, N, Joly-Beauparlant, C, Ernst, C, Droit, A, Feng, B-J, Dubois, S, Collin-Deschesnes, A-C, Soucy, P, Vallée, M, Fournier, F, Lemaçon, A, Adank, MA, Allen, J, Altmüller, J, Arnold, N, Ausems, MGEM, Berutti, R, Bolla, MK, Bull, S, Carvalho, S, Cornelissen, S, Dufault, MR, Dunning, AM, Engel, C, Gehrig, A, Geurts-Giele, WRR, Gieger, C, Green, J, Hackmann, K, Helmy, M, Hentschel, J, Hogervorst, FBL, Hollestelle, A, Hooning, MJ, Horváth, J, Ikram, MA, Kaulfuß, S, Keeman, R, Kuang, D, Luccarini, C, Maier, W, Martens, JWM, Niederacher, D, Nürnberg, P, Ott, C-E, Peters, A, Pharoah, PDP, Ramirez, A, Ramser, J, Riedel-Heller, S, Schmidt, G, Shah, M, Scherer, M, Stäbler, A, Strom, TM, Sutter, C, Thiele, H, van Asperen, CJ, van der Kolk, L, van der Luijt, RB, Volk, AE, Wagner, M, Waisfisz, Q, Wang, Q, Wang-Gohrke, S, Weber, BHF, Genome Of The Netherlands Project, Ghs Study Group, Devilee, P, Tavtigian, S, Bader, GD, Meindl, A, Goldgar, DE, Andrulis, IL, Schmutzler, RK, Easton, DF, Schmidt, MK, Hahnen, E, and Simard, J
Abstract: Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.
Published: 2022

12. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
Published: 2022

13. A saturated map of common genetic variants associated with human height

Author: Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022

14. Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, and Debette, S
Published: 2022

15. Past, Present, and Future of Informed Consent in Pain and Genomics Research: Challenges Facing Global Medical Community

Author: Compagnone, Christian, Schatman, Michael E., Rauck, Richard L., Van Zundert, Jan, Kraus, Monika, Primorac, Dragan, Williams, Frances, Allegri, Massimo, Saccani Jordi, Gloria, Fanelli, Guido, Skelin, A., Perović, D., Houra, K., Granec, D., Minella, C., DeGregori, M., Hong, Jason, Baciarello, M., Marchesini, M., Vanelderen, P., Kovačić, S., Rotim, K., Gieger, C., Aulchenko, Y., Pemberton, I.K., MacDougal, J., and Black, M.
Published: 2017
Full Text: View/download PDF

16. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

Author: Cornelis, M C, Byrne, E M, Esko, T, Nalls, M A, Ganna, A, Paynter, N, Monda, K L, Amin, N, Fischer, K, Renstrom, F, Ngwa, J S, Huikari, V, Cavadino, A, Nolte, I M, Teumer, A, Yu, K, Marques-Vidal, P, Rawal, R, Manichaikul, A, Wojczynski, M K, Vink, J M, Zhao, J H, Burlutsky, G, Lahti, J, Mikkilä, V, Lemaitre, R N, Eriksson, J, Musani, S K, Tanaka, T, Geller, F, Luan, J, Hui, J, Mägi, R, Dimitriou, M, Garcia, M E, Ho, W-K, Wright, M J, Rose, L M, Magnusson, P K E, Pedersen, N L, Couper, D, Oostra, B A, Hofman, A, Ikram, M A, Tiemeier, H W, Uitterlinden, A G, van Rooij, F J A, Barroso, I, Johansson, I, Xue, L, Kaakinen, M, Milani, L, Power, C, Snieder, H, Stolk, R P, Baumeister, S E, Biffar, R, Gu, F, Bastardot, F, Kutalik, Z, Jacobs, Jr, D R, Forouhi, N G, Mihailov, E, Lind, L, Lindgren, C, Michaëlsson, K, Morris, A, Jensen, M, Khaw, K-T, Luben, R N, Wang, J J, Männistö, S, Perälä, M-M, Kähönen, M, Lehtimäki, T, Viikari, J, Mozaffarian, D, Mukamal, K, Psaty, B M, Döring, A, Heath, A C, Montgomery, G W, Dahmen, N, Carithers, T, Tucker, K L, Ferrucci, L, Boyd, H A, Melbye, M, Treur, J L, Mellström, D, Hottenga, J J, Prokopenko, I, Tönjes, A, Deloukas, P, Kanoni, S, Lorentzon, M, Houston, D K, Liu, Y, Danesh, J, Rasheed, A, Mason, M A, Zonderman, A B, Franke, L, Kristal, B S, Karjalainen, J, Reed, D R, Westra, H-J, Evans, M K, Saleheen, D, Harris, T B, Dedoussis, G, Curhan, G, Stumvoll, M, Beilby, J, Pasquale, L R, Feenstra, B, Bandinelli, S, Ordovas, J M, Chan, A T, Peters, U, Ohlsson, C, Gieger, C, Martin, N G, Waldenberger, M, Siscovick, D S, Raitakari, O, Eriksson, J G, Mitchell, P, Hunter, D J, Kraft, P, Rimm, E B, Boomsma, D I, Borecki, I B, Loos, R J F, Wareham, N J, Vollenweider, P, Caporaso, N, Grabe, H J, Neuhouser, M L, Wolffenbuttel, B H R, Hu, F B, Hyppönen, E, Järvelin, M-R, Cupples, L A, Franks, P W, Ridker, P M, van Duijn, C M, Heiss, G, Metspalu, A, North, K E, Ingelsson, E, Nettleton, J A, van Dam, R M, and Chasman, D I
Published: 2015
Full Text: View/download PDF

17. Validation of the 30-year Framingham Risk Score in a German population-based cohort

Author: Rospleszcz, S., Starnecker, F., Linkohr, B., von Scheidt, M., Gieger, C., Schunkert, H., Peters, A., DigiMed Bayern Consortium (Adam, J.), DigiMed Bayern Consortium (Berutti, R.), and DigiMed Bayern Consortium (Brandmaier, S.)
Subjects: Clinical Biochemistry, risk prediction, risk factors, cardiovascular disease, cohort study, calibration, Article, Calibration, Cardiovascular Disease, Cohort Study, Risk Factors, Risk Prediction, ddc
Abstract: The Framingham Risk Score to predict 30-year risk (FRS30y) of cardiovascular disease (CVD) constitutes an important tool for long-term risk prediction. However, due to its complex statistical properties and the paucity of large population-based cohorts with appropriate data, validation of the FRS30y is lacking. A population-based cohort from Southern Germany (N = 3110, 1516 (48.7%) women) was followed up for a median time of 29.5 [18.7, 31.2] years. Discrimination and calibration were assessed for the original, recalibrated and refitted FRS30y version. During follow up, 620 incident CVD events (214 in women) occurred. The FRS30y showed adequate discrimination (original and recalibrated version: Area under the curve (AUC): 78.4 for women and 74.9 for men) but overestimated actual CVD risk (original version: discordance 45.4% for women and 37.3% for men, recalibrated version: 37.6% and 28.6%, respectively). Refitting showed substantial improvement in neither discrimination nor calibration. The performance of FRS30y is adequate for long-term CVD risk prediction and could serve as an important tool in risk communication, especially for younger audiences.
Published: 2022

18. Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up

Author: Mook-Kanamori, D. O., Römisch-Margl, W., Kastenmüller, G., Prehn, C., Petersen, A. K., Illig, T., Gieger, C., Wang-Sattler, R., Meisinger, C., Peters, A., Adamski, J., and Suhre, K.
Published: 2014
Full Text: View/download PDF

19. Heritability of young- and old-onset ischaemic stroke

Author: Bluher, A., Devan, W. J., Holliday, E. G., Nalls, M., Parolo, S., Bione, S., Giese, A.-K., Boncoraglio, G. B., Maguire, J. M., Müller-Nurasyid, M., Gieger, C., Meschia, J. F., Rosand, J., Rolfs, A., Kittner, S. J., Mitchell, B. D., OʼConnell, J. R., and Cheng, Y.-C.
Published: 2015
Full Text: View/download PDF

20. Genome-wide characterization of a highly penetrant form of hyperlipoprotein(a)emia causatively associated with genetically elevated cardiovascular risk

Author: Chemello, K., primary, Coassin, S., additional, Khantalin, I., additional, Gieger, C., additional, Peters, A., additional, Zschocke, J., additional, Lamina, C., additional, and Lambert, G., additional
Published: 2021
Full Text: View/download PDF

21. Replication of fifteen loci involved in human plasma protein N-glycosylation in 4,802 samples from four cohorts

Author: Sharapov, S.Z., Shadrina, A.S., Tsepilov, Y.A., Elgaeva, E.E., Tiys, E.S., Feoktistova, S.G., Zaytseva, O.O., Vučković, F., Cuadrat, R., Jäger, S., Wittenbecher, C., Karssen, L.C., Timofeeva, M., Tillin, T., Trbojević-Akmačić, I., Štambuk, T., Rudman, N., Krištić, J., Šimunović, J., Momčilović, A., Vilaj, M., Jurić, J., Slana, A., Gudelj, I., Klarić, T., Puljak, L., Skelin, A., Kadić, A.J., Van Zundert, J., Chaturvedi, N., Campbell, H., Dunlop, M., Farrington, S.M., Doherty, M., Dagostino, C., Gieger, C., Allegri, M., Williams, F., Schulze, M.B., Lauc, G., and Aulchenko, Y.S.
Subjects: Genetic Association Study, Glycosylation, Locus, Replication, Total Plasma N-glycome
Abstract: Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identified by three previous GWAS of human plasma proteome N-glycosylation. However, the possibility that some of these loci are false positives needs to be eliminated by replication studies, which have been limited so far. Here, we use the largest set of samples so far (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen were replicated in our study. For the remaining locus (near the KREMEN1 gene) the replication power was low, and hence replication results were inconclusive. The very high replication rate highlights the general robustness of the GWAS findings as well as the high standards adopted by the community that studies genetic regulation of protein glycosylation. The fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode glycosyltransferases: MGAT5, B3GAT1, FUT8, FUT6, ST6GAL1, B4GALT1, ST3GAL4, and MGAT3. The remaining seven loci offer starting points for further functional follow-up investigation into molecules and mechanisms that regulate human protein N-glycosylation in vivo.
Published: 2021

22. Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Author: Zhou, B, Carrillo-Larco, Rm, Danaei, G, Riley, Lm, Paciorek, Cj, Stevens, Ga, Gregg, Ew, Bennett, Je, Solomon, B, Singleton, Rk, Sophiea, Mk, Iurilli, Mlc, Lhoste, Vpf, Cowan, Mj, Savin, S, Woodward, M, Balanova, Y, Cifkova, R, Damasceno, A, Elliott, P, Farzadfar, F, He, J, Ikeda, N, Kengne, Ap, Khang, Yh, Kim, Hc, Laxmaiah, A, Lin, Hh, Maira, Pm, Miranda, Jj, Neuhauser, H, Sundstrom, J, Varghese, C, Widyahening, Is, Zdrojewski, T, Ezzati, M, Abarca-Gomez, L, Abdeen, Za, Rahim, Hfa, Abu-Rmeileh, Nm, Acosta-Cazares, B, Adams, Rj, Aekplakorn, W, Afsana, K, Afzal, S, Agdeppa, Ia, Aghazadeh-Attari, J, Aguilar-Salinas, Ca, Agyemang, C, Ahmad, Na, Ahmadi, A, Ahmadi, N, Ahmadizar, F, Ahmed, Sh, Ahrens, W, Ajlouni, K, Al-Raddadi, R, Alarouj, M, Albuhairan, F, Aldhukair, S, Ali, Mm, Alkandari, A, Alkerwi, A, Allin, K, Aly, E, Amarapurkar, Dn, Amougou, N, Amouyel, P, Andersen, Lb, Anderssen, Sa, Anjana, Rm, Ansari-Moghaddam, A, Ansong, D, Aounallah-Skhiri, H, Araujo, J, Ariansen, I, Aris, T, Arku, Re, Arlappa, N, Aryal, Kk, Aspelund, T, Assah, Fk, Assuncao, Mcf, Auvinen, J, Avdicova, M, Azevedo, A, Azimi-Nezhad, M, Azizi, F, Azmin, M, Babu, Bv, Bahijri, S, Balakrishna, N, Bamoshmoosh, M, Banach, M, Banadinovic, M, Bandosz, P, Banegas, Jr, Baran, J, Barbagallo, Cm, Barcelo, A, Barkat, A, Barreto, M, Barros, Ajd, Barros, Mvg, Bartosiewicz, A, Basit, A, Bastos, Jld, Bata, I, Batieha, Am, Batyrbek, A, Baur, La, Beaglehole, R, Belavendra, A, Ben Romdhane, H, Benet, M, Benson, Ls, Berkinbayev, S, Bernabe-Ortiz, A, Bettiol, H, Bezerra, J, Bhagyalaxmi, A, Bhargava, Sk, Bia, D, Biasch, K, Lele, Ecb, Bikbov, Mm, Bista, B, Bjerregaard, P, Bjertness, E, Bjertness, Mb, Bjorkelund, C, Bloch, Kv, Blokstra, A, Bo, S, Bobak, M, Boeing, H, Boggia, Jg, Boissonnet, Cp, Bojesen, Se, Bongard, V, Bonilla-Vargas, A, Bopp, M, Borghs, H, Bovet, P, Boyer, Cb, Braeckman, L, Brajkovich, I, Branca, F, Breckenkamp, J, Brenner, H, Brewster, Lm, Briceno, Y, Brito, M, Bruno, G, Bueno-de-Mesquita, Hb, Bueno, G, Bugge, A, Burns, C, Bursztyn, M, de Leon, Ac, Cacciottolo, J, Cameron, C, Can, G, Candido, Apc, Capanzana, Mv, Capkova, N, Capuano, E, Capuano, V, Cardoso, Vc, Carlsson, Ac, Carvalho, J, Casanueva, Ff, Censi, L, Cervantes-Loaiza, M, Chadjigeorgiou, Ca, Chamukuttan, S, Chan, Aw, Chan, Q, Chaturvedi, Hk, Chaturvedi, N, Chee, Ml, Chen, Cj, Chen, Ff, Chen, Hs, Chen, Sh, Chen, Zm, Cheng, Cy, Cheraghian, B, Dekkaki, Ic, Chetrit, A, Chien, Kl, Chiolero, A, Chiou, St, Chirita-Emandi, A, Chirlaque, Md, Cho, B, Christensen, K, Christofaro, Dg, Chudek, J, Cinteza, E, Claessens, F, Clarke, J, Clays, E, Cohen, E, Concin, H, Cooper, C, Coppinger, Tc, Costanzo, S, Cottel, D, Cowell, C, Craig, Cl, Crampin, Ac, Crujeiras, Ab, Cruz, Jj, Csilla, S, Cui, Lf, Cureau, Fv, Cuschieri, S, D'Arrigo, G, D'Orsi, E, Dallongeville, J, Dankner, R, Dantoft, Tm, Dauchet, L, Davletov, K, De Backer, G, De Bacquer, D, De Curtis, A, de Gaetano, G, De Henauw, S, de Oliveira, Pd, De Ridder, D, De Smedt, D, Deepa, M, Deev, Ad, Degennaro, V, Delisle, H, Demarest, S, Dennison, E, Deschamps, V, Dhimal, M, Di Castelnuovo, Af, Dias-da-Costa, Js, Diaz, A, Dickerson, Tt, Dika, Z, Djalalinia, S, Htp, Do, Dobson, Aj, Donfrancesco, C, Donoso, Sp, Doring, A, Dorobantu, M, Dorr, M, Doua, K, Dragano, N, Drygas, W, Duante, Ca, Duboz, P, Duda, Rb, Dulskiene, V, Dushpanova, A, Dzakula, A, Dzerve, V, Dziankowska-Zaborszczyk, E, Eddie, R, Eftekhar, E, Eggertsen, R, Eghtesad, S, Eiben, G, Ekelund, U, El-Khateeb, M, El Ati, J, Eldemire-Shearer, D, Eliasen, M, Elosua, R, Erasmus, Rt, Erbel, R, Erem, C, Eriksen, L, Eriksson, Jg, Escobedo-de la Pena, J, Eslami, S, Esmaeili, A, Evans, A, Faeh, D, Fakhretdinova, Aa, Fall, Ch, Faramarzi, E, Farjam, M, Fattahi, Mr, Fawwad, A, Felix-Redondo, Fj, Felix, Sb, Ferguson, Ts, Fernandes, Ra, Fernandez-Berges, D, Ferrante, D, Ferrao, T, Ferrari, M, Ferrario, Mm, Ferreccio, C, Ferreira, Hs, Ferrer, E, Ferrieres, J, Figueiro, Th, Fink, G, Fischer, K, Foo, Lh, Forsner, M, Fouad, Hm, Francis, Dk, Grego, Franco, Frikke-Schmidt, R, Frontera, G, Fuchs, Fd, Fuchs, Sc, Fujita, Y, Fumihiko, M, Furdela, V, Furer, A, Furusawa, T, Gaciong, Z, Galbarczyk, A, Galenkamp, H, Galvano, F, Gao, Jl, Gao, P, Garcia-de-la-Hera, M, Garcia, P, Gareta, D, Garnett, Sp, Gaspoz, Jm, Gasull, M, Gazzinelli, A, Gehring, U, Geleijnse, Jm, George, R, Ghanbari, A, Ghasemi, E, Gheorghe-Fronea, Of, Ghimire, A, Gialluisi, A, Giampaoli, S, Gieger, C, Gill, Tk, Giovannelli, J, Gironella, G, Giwercman, A, Gkiouras, K, Goldberg, M, Goldsmith, Ra, Gomez, Lf, Gomula, A, da Silva, Bgc, Goncalves, H, Goncalves, M, Gonzalez-Chica, Da, Gonzalez-Gross, M, Gonzalez-Rivas, Jp, Gonzalez-Villalpando, C, Gonzalez-Villalpando, Me, Gonzalez, Ar, Gorbea, Mb, Gottrand, F, Graff-Iversen, S, Grafnetter, D, Grajda, A, Grammatikopoulou, Mg, Gregor, Rd, Grodzicki, T, Grosso, G, Gruden, G, Df, Gu, Guan, Op, Gudmundsson, Ef, Gudnason, V, Guerrero, R, Guessous, I, Guimaraes, Al, Gulliford, Mc, Gunnlaugsdottir, J, Gunter, Mj, Gupta, Pc, Gupta, R, Gureje, O, Gurzkowska, B, Gutierrez, L, Gutzwiller, F, Ha, S, Hadaegh, F, Haghshenas, R, Hakimi, H, Halkjaer, J, Hambleton, Ir, Hamzeh, B, Hange, D, Hanif, Aam, Hantunen, S, Hao, J, Hardman, Cm, Kumar, Rh, Hashemi-Shahri, Sm, Hata, J, Haugsgjerd, T, Hayes, Aj, Yn, He, Heier, M, Hendriks, Me, Henrique, Rd, Henriques, A, Cadena, Lh, Herrala, S, Heshmat, R, Hill, Ag, Sy, Ho, Sc, Ho, Hobbs, M, Holdsworth, M, Homayounfar, R, Dinc, Gh, Horimoto, Arvr, Hormiga, Cm, Horta, Bl, Houti, L, Howitt, C, Htay, Tt, Htet, As, Htike, Mmt, Yh, Hu, Huerta, Jm, Huhtaniemi, It, Huiart, L, Huisman, M, Husseini, As, Huybrechts, I, Hwalla, N, Iacoviello, L, Iannone, Ag, Ibrahim, Mm, Wong, Ni, Ikram, Ma, Iotova, V, Irazola, Ve, Ishida, T, Isiguzo, Gc, Islam, M, Islam, Sms, Iwasaki, M, Jackson, Rt, Jacobs, Jm, Jaddou, Hy, Jafar, T, James, K, Jamrozik, K, Janszky, I, Janus, E, Jarvelin, Mr, Jasienska, G, Jelakovic, A, Jelakovic, B, Jennings, G, Jha, Ak, Jiang, Cq, Jimenez, Ro, Jockel, Kh, Joffres, M, Johansson, M, Jokelainen, Jj, Jonas, Jb, Jorgensen, T, Joshi, P, Joukar, F, Jozwiak, J, Juolevi, A, Jurak, G, Juresa, V, Kaaks, R, Kafatos, A, Kajantie, Eo, Kalmatayeva, Z, Kalpourtzi, N, Kalter-Leibovici, O, Kampmann, Fb, Kannan, S, Karaglani, E, Karhus, Ll, Karki, Kb, Katibeh, M, Katz, J, Kauhanen, J, Kaur, P, Kavousi, M, Kazakbaeva, Gm, Keil, U, Boker, Lk, Keinanen-Kiukaanniemi, S, Kelishadi, R, Kemper, Hcg, Keramati, M, Kerimkulova, A, Kersting, M, Key, T, Khader, Ys, Khalili, D, Khaw, Kt, Kheiri, B, Kheradmand, M, Khosravi, A, Kiechl-Kohlendorfer, U, Kiechl, S, Killewo, J, Kim, Dw, Kim, J, Klakk, H, Klimek, M, Klumbiene, J, Knoflach, M, Kolle, E, Kolsteren, P, Kontto, Jp, Korpelainen, R, Korrovits, P, Kos, J, Koskinen, S, Kouda, K, Kowlessur, S, Koziel, S, Kratenova, J, Kriaucioniene, V, Kristensen, Pl, Krokstad, S, Kromhout, D, Kruger, Hs, Kubinova, R, Kuciene, R, Kujala, Um, Kulaga, Z, Kumar, Rk, Kurjata, P, Kusuma, Ys, Kutsenko, V, Kuulasmaa, K, Kyobutungi, C, Laatikainen, T, Lachat, C, Laid, Y, Lam, Th, Landrove, O, Lanska, V, Lappas, G, Larijani, B, Latt, Ts, Le Coroller, G, Bao, Kln, Le, THUY DUNG, Lee, J, Lehmann, N, Lehtimaki, T, Lemogoum, D, Levitt, Ns, Yp, Li, Lilly, Cl, Lim, Wy, Lima-Costa, Mf, Lin, X, Lin, Yt, Lind, L, Lingam, V, Linneberg, A, Lissner, L, Litwin, M, Wc, Lo, Loit, Hm, Lopez-Garcia, E, Lopez, T, Lotufo, Pa, Lozano, Je, Lovrencic, Il, Lukrafka, Jl, Luksiene, D, Lundqvist, A, Lundqvist, R, Lunet, N, Lustigova, M, Luszczki, E, Gs, Ma, Ma, J, Machado-Coelho, Gll, Machado-Rodrigues, Am, Macia, E, Macieira, Lm, Madar, Aa, Maggi, S, Magliano, Dj, Magriplis, E, Mahasampath, G, Maire, B, Majer, M, Makdisse, M, Malekzadeh, F, Malekzadeh, R, Malhotra, R, Mallikharjuna, K, Malyutina, Sk, Maniego, Lv, Manios, Y, Mann, Ji, Mansour-Ghanaei, F, Manzato, E, Marcil, A, Margozzini, P, Marild, Sb, Glavic, Mm, Marques-Vidal, P, Marques, Lp, Marrugat, J, Martorell, R, Mascarenhas, Lp, Matasin, M, Mathiesen, Eb, Mathur, P, Matijasevich, A, Matlosz, P, Matsha, Te, Mavrogianni, C, Mbanya, Jcn, Posso, Ajm, Mcfarlane, Sr, Mcgarvey, St, Mclachlan, S, Mclean, Rm, Mclean, Sb, Mcnulty, Ba, Benchekor, Sm, Medzioniene, J, Mehdipour, P, Mehlig, K, Mehrparvar, Ah, Meirhaeghe, A, Meisinger, C, Montano, Cm, Menezes, Amb, Menon, Gr, Mereke, A, Meshram, Ii, Metspalu, A, Meyer, He, Mi, J, Michels, N, Mikkel, K, Milkowska, K, Miller, Jc, Minderico, Cs, Mini, Gk, Mirjalili, Mr, Mirrakhimov, E, Misigoj-Durakovic, M, Modesti, Pa, Moghaddam, Ss, Mohajer, B, Mohamed, Mk, Mohamed, Sf, Mohammad, K, Mohammadi, Mr, Mohammadi, Z, Mohammadifard, N, Mohammadpourhodki, R, Mohan, V, Mohanna, S, Yusoff, Mfm, Mohebbi, I, Mohebi, F, Moitry, M, Mollehave, Lt, Molnar, D, Momenan, A, Mondo, Ck, Monterrubio-Flores, E, Monyeki, Kdk, Moon, Js, Moosazadeh, M, Moreira, Lb, Morejon, A, Moreno, La, Morgan, K, Moschonis, G, Mossakowska, M, Mostafa, A, Mostafavi, Sa, Mota, J, Motlagh, Me, Motta, J, Moura-dos-Santos, Ma, Mridha, Mk, Msyamboza, Kp, Tt, Mu, Muhihi, Aj, Muiesan, Ml, Muller-Nurasyid, M, Murphy, N, Mursu, J, Musa, Ki, Milanovic, Sm, Musil, V, Mustafa, N, Nabipour, I, Naderimagham, S, Nagel, G, Naidu, Bm, Najafi, F, Nakamura, H, Namesna, J, Nang, Eek, Nangia, Vb, Narake, S, Ndiaye, Nc, Neal, Wa, Nejatizadeh, A, Nenko, I, Neovius, M, Neuhauser, Hk, Nguyen, Ct, Nguyen, Nd, Nguyen, Qv, Nguyen, Qn, Nieto-Martinez, Re, Niiranen, Tj, Nikitin, Yp, Ninomiya, T, Nishtar, S, Njelekela, Ma, Noale, M, Noboa, Oa, Noorbala, Aa, Norat, T, Nordendahl, M, Nordestgaard, Bg, Noto, D, Nowak-Szczepanska, N, Al Nsour, M, Nunes, B, O'Neill, Tw, O'Reilly, D, Ochimana, C, Oda, E, Odili, An, Oh, K, Ohara, K, Ohtsuka, R, Olie, V, Olinto, Mta, Oliveira, Io, Omar, Ma, Onat, A, Ong, Sk, Ono, Lm, Ordunez, P, Ornelas, R, Ortiz, Pj, Osmond, C, Ostojic, Sm, Ostovar, A, Otero, Ja, Overvad, K, Owusu-Dabo, E, Paccaud, Fm, Padez, C, Pahomova, E, de Paiva, Km, Pajak, A, Palli, D, Palmieri, L, Pan, Wh, Panda-Jonas, S, Panza, F, Paoli, M, Papandreou, D, Park, Sw, Park, S, Parnell, Wr, Parsaeian, M, Pasquet, P, Patel, Nd, Pavlyshyn, H, Pecin, I, Pednekar, Ms, Pedro, Jm, Peer, N, Peixoto, Sv, Peltonen, M, Pereira, Ac, Peres, Kgda, Peres, Ma, Peters, A, Petkeviciene, J, Peykari, N, Pham, St, Pichardo, Rn, Pigeot, I, Pikhart, H, Pilav, A, Pilotto, L, Pitakaka, F, Piwonska, A, Pizarro, An, Plans-Rubio, P, Polasek, O, Porta, M, Poudyal, A, Pourfarzi, F, Pourshams, A, Poustchi, H, Pradeepa, R, Price, Aj, Price, Jf, Providencia, R, Puhakka, Se, Puiu, M, Punab, M, Qasrawi, Rf, Qorbani, M, Queiroz, D, Bao, Tq, Radic, I, Radisauskas, R, Rahimikazerooni, S, Rahman, M, Raitakari, O, Raj, M, Rakhimova, Em, Rao, Sr, Ramachandran, A, Ramos, E, Rampal, L, Rampal, S, Reina, Dar, Rarra, V, Rech, Cr, Redon, J, Reganit, Pfm, Regecova, V, Revilla, L, Rezaianzadeh, A, Ribeiro, R, Riboli, E, Richter, A, Rigo, F, de Wit, Tfr, Ritti-Dias, Rm, Robitaille, C, Rodriguez-Artalejo, F, Rodriguez-Perez, Md, Rodriguez-Villamizar, La, Roggenbuck, U, Rojas-Martinez, R, Romaguera, D, Romeo, El, Rosengren, A, Roy, Jgr, Rubinstein, A, Ruidavets, Jb, Ruiz-Betancourt, Bs, Ruiz-Castell, M, Rusakova, Ia, Russo, P, Rutkowski, M, Sabanayagam, C, Sabbaghi, H, Sachdev, Hs, Sadjadi, A, Safarpour, Ar, Safi, S, Safiri, S, Saidi, O, Sakarya, S, Saki, N, Salanave, B, Martinez, Es, Salmeron, D, Salomaa, V, Salonen, Jt, Salvetti, M, Sanchez-Abanto, J, Sans, S, Santos, Da, Santos, Is, Santos, Lc, Santos, Mp, Santos, R, Saramies, Jl, Sardinha, Lb, Sarganas, G, Sarrafzadegan, N, Sathish, T, Saum, Ku, Savva, S, Sawada, N, Sbaraini, M, Scazufca, M, Schaan, Bd, Schargrodsky, H, Schipf, S, Schmidt, Co, Schnohr, P, Schottker, B, Schramm, S, Schultsz, C, Schutte, Ae, Sebert, S, Sein, Aa, Sen, A, Senbanjo, Io, Sepanlou, Sg, Servais, J, Shalnova, Sa, Shamah-Levy, T, Shamshirgaran, M, Shanthirani, Cs, Sharafkhah, M, Sharma, Sk, Shaw, Je, Shayanrad, A, Shayesteh, Aa, Shi, Zm, Shibuya, K, Shimizu-Furusawa, H, Shin, Dw, Shirani, M, Shiri, R, Shrestha, N, Si-Ramlee, K, Siani, A, Siantar, R, Sibai, Am, Silva, Crd, Silva, Das, Simon, M, Simons, J, Simons, La, Sjostrom, M, Slowikowska-Hilczer, J, Slusarczyk, P, Smeeth, L, Hk, So, Soares, Fc, Sobngwi, E, Soderberg, S, Soemantri, A, Sofat, R, Solfrizzi, V, Somi, Mh, Sonestedt, E, Song, Y, Sorensen, Tia, Sorgjerd, Ep, Soric, M, Jerome, Cs, Soumare, A, Sparboe-Nilsen, B, Sparrenberger, K, Staessen, Ja, Starc, G, Stavreski, B, Steene-Johannessen, J, Stehle, P, Stein, Ad, Stergiou, Gs, Stessman, J, Stieber, J, Stockl, D, Stocks, T, Stokwiszewski, J, Stronks, K, Strufaldi, Mw, Suka, M, Sun, Ca, Sung, Yt, Suriyawongpaisal, P, Rg, Sy, Syddall, He, Sylva, Rc, Szklo, M, Tai, Es, Tammesoo, Ml, Tamosiunas, A, Tan, Ej, Tang, X, Tanser, F, Tao, Y, Tarawneh, Mr, Tarqui-Mamani, Cb, Taylor, A, Taylor, J, Tebar, Wr, Tell, Gs, Tello, T, Tham, Yc, Thankappan, Kr, Theobald, H, Theodoridis, X, Thijs, L, Thinggaard, M, Thomas, N, Thorand, B, Thuesen, Bh, Timmermans, Ej, Tjandrarini, Dh, Tjonneland, A, Toft, U, Tolonen, Hk, Tolstrup, Js, Topbas, M, Topor-Madry, R, Tormo, Mj, Tornaritis, Mj, Torrent, M, Torres-Collado, L, Touloumi, G, Traissac, P, Triantafyllou, A, Trichopoulos, D, Trichopoulou, A, Trinh, Oth, Trivedi, A, Tshepo, L, Tsugane, S, Tuliakova, Am, Tulloch-Reid, Mk, Tullu, F, Tuomainen, Tp, Tuomilehto, J, Turley, Ml, Twig, G, Tynelius, P, Tzourio, C, Ueda, P, Ugel, E, Ulmer, H, Uusitalo, Hmt, Valdivia, G, Valvi, D, van Dam, Rm, van den Born, Bj, Van der Heyden, J, van der Schouw, Yt, Van Herck, K, Minh, Hv, Van Schoor, Nm, van Valkengoed, Igm, van Zutphen, Em, Vanderschueren, D, Vanuzzo, D, Varbo, A, Vasan, Sk, Vega, T, Veidebaum, T, Velasquez-Melendez, G, Veronesi, G, Verschuren, Wmm, Verstraeten, R, Victora, Cg, Viet, L, Villalpando, S, Vineis, P, Vioque, J, Virtanen, Jk, Visvikis-Siest, S, Viswanathan, B, Vlasoff, T, Vollenweider, P, Voutilainen, A, Wade, An, Walton, J, Wambiya, Eoa, Bebakar, Wmw, Mohamud, Wnw, Wanderley, Rd, Wang, Md, Wang, Nl, Wang, Q, Wang, Xj, Wang, Yx, Wang, Yw, Wannamethee, Sg, Wareham, N, Wei, Wb, Weres, A, Werner, B, Whincup, Ph, Widhalm, K, Wiecek, A, Wilks, Rj, Willeit, J, Willeit, P, Williams, Ea, Wilsgaard, T, Wojtyniak, B, Wong-McClure, Ra, Wong, A, Wong, Ty, Woo, J, Fc, Wu, Sl, Wu, Wyszynska, J, Hq, Xu, Xu, L, Yaacob, Na, Yan, Wl, Yang, L, Yang, Xg, Yang, Y, Yasuharu, T, Xw, Ye, Yiallouros, Pk, Yoosefi, M, Yoshihara, A, You, Sl, Younger-Coleman, No, Yusoff, Af, Zainuddin, Aa, Zakavi, Sr, Zamani, F, Zambon, S, Zampelas, A, Zapata, Me, Zaw, Kk, Zejglicova, K, Vrkic, Tz, Zeng, Y, Zhang, Lx, Zhang, Zy, Zhao, D, Zhao, Mh, Zhen, Sq, Zheng, Yf, Zholdin, B, Zhu, D, Zins, M, Zitt, E, Zocalo, Y, Zoghlami, N, Cisneros, Jz, Borghs, Herman, Claessens, Frank, Staessen, Jan, Thijs, Lutgarde, Vanderschueren, Dirk, Zhang, Zhen-Yu, Imperial Coll London, Harvard TH Chan Sch Publ Hlth, WHO, Univ Calif Berkeley, Univ New South Wales, Natl Med Res Ctr Therapy & Prevent Med, Charles Univ Prague, Thomayer Hosp, Eduardo Mondlane Univ, Noncommunicable Dis Res Ctr, Tulane Univ, Natl Inst Biomed Innovat Hlth & Nutr, South African Med Res Council, Seoul Natl Univ, Yonsei Univ, ICMR Natl Inst Nutr, Natl Taiwan Univ, Pontificia Univ Catolica Chile, Univ Peruana Cayetano Heredia, Robert Koch Inst, Uppsala Univ, Univ Indonesia, Med Univ Gdansk, Univ Ghana, Caja Costarricense Seguro Social, Al Quds Univ, Qatar Univ, Birzeit Univ, Inst Mexicano Seguro Social, Flinders Univ S Australia, Mahidol Univ, BRAC Univ, Univ Copenhagen, Copenhagen Univ Hosp, Food & Nutr Res Inst, Urmia Univ Med Sci, Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Univ Amsterdam, Minist Hlth, Modeling Hlth Res Ctr, Shahid Sadoughi Univ Med Sci, Erasmus MC, Univ Oslo, Leibniz Inst Prevent Res & Epidemiol BIPS, Natl Ctr Diabet Endocrinol & Genet, King Abdulaziz Univ, Dasman Diabet Inst, Aldara Hosp & Med Ctr, King Abdullah Int Med Res Ctr, Luxembourg Inst Hlth, Bispebjerg, Frederiksberg Univ Hosp, WHO Reg Off Eastern Mediterranean, Bombay Hosp & Med Res Ctr, CNRS, Univ Lille, Lille Univ Hosp, Western Norway Univ Appl Sci, Norwegian Sch Sport Sci, Madras Diabet Res Fdn, Zahedan Univ Med Sci, Kwame Nkrumah Univ Sci & Technol, Natl Inst Publ Hlth, Univ Porto, Norwegian Inst Publ Hlth, Univ Massachusetts, Abt Associates Inc, Univ Iceland, Univ Yaounde I, Univ Fed Pelotas, Univ Oulu, Oulu Univ Hosp, Banska Bystr Reg Author Publ Hlth, Neyshabur Univ Med Sci, Res Inst Endocrine Sci, Indian Council Med Res, Univ Sci & Technol, Med Univ Lodz, Univ Zagreb, Univ Autonoma Madrid CIBERESP, Univ Rzeszow, Univ Palermo, Pan Amer Hlth Org, Mohammed V Univ Rabat, Natl Inst Hlth Doutor Ricardo Jorge, NOVA Univ Lisbon, Univ Pernambuco, Baqai Inst Diabetol & Endocrinol, Universidade Federal de Santa Catarina (UFSC), Dalhousie Univ, Jordan Univ Sci & Technol, Al Farabi Kazakh Natl Univ, Univ Sydney, Univ Auckland, Christian Med Coll Vellore, Univ Tunis El Manar, Cafam Univ Fdn, Univ Utah, Kazakh Natl Med Univ, Lithuanian Univ Hlth Sci, Universidade de São Paulo (USP), BJ Med Coll, Sunder Lal Jain Hosp, Univ Republica, Univ Strasbourg, Inst Med Res & Med Plant Studies, Ufa Eye Res Inst, Nepal Hlth Res Council, Univ Southern Denmark, Univ Gothenburg, Universidade Federal do Rio de Janeiro (UFRJ), Natl Inst Publ Hlth & Environm, Univ Turin, UCL, German Inst Human Nutr, Ctr Educ Med & Invest Clin, Toulouse Univ, Univ Zurich, Univ Hosp KU Leuven, Unisante, Univ Ghent, Univ Cent Venezuela, Bielefeld Univ, German Canc Res Ctr, Univ Andres, Inst Politecn Lisboa, Univ Zaragoza, Univ Coll Copenhagen, Munster Technol Univ, Hadassah Univ, Univ La Laguna, Univ Malta, Canadian Fitness & Lifestyle Res Inst, Istanbul Univ Cerrahpasa, Univ Fed Juiz de Fora, Gaetano Fucito Hosp, Karolinska Inst, Santiago Compostela Univ, Council Agr Res & Econ, Res & Educ Inst Child Hlth, India Diabet Res Fdn, Duke NUS Med Sch, ICMR Natl Inst Med Stat, Singapore Eye Res Inst, Acad Sinica, Capital Inst Pediat, Duke Univ, Kailuan Gen Hosp, Univ Oxford, Ahvaz Jundishapur Univ Med Sci, Gertner Inst Epidemiol & Hlth Policy Res, Univ Bern, Minist Hlth & Welf, Victor Babes Univ Med & Pharm Timisoara, CIBER Epidemiol & Salud Publ, Universidade Estadual Paulista (UNESP), Med Univ Silesia, Carol Davila Univ Med & Pharm, Katholieke Univ Leuven, STAT Canada, Agcy Prevent & Social Med, Univ Southampton, IRCCS Neuromed, Inst Pasteur, Malawi Epidemiol & Intervent Res Unit, CIBEROBN, Univ Autonoma Madrid, Univ Debrecen, Univ Fed Rio Grande do Sul, CNR, Geneva Univ Hosp, Innovating Hlth Int, Univ Montreal, Sciensano, French Publ Hlth Agcy, Mediterranea Cardioctr, Univ Vale Rio dos Sinos, Natl Council Sci & Tech Res, Minist Hlth & Med Educ, Natl Inst Nutr, Univ Queensland, Ist Super Sanita, Univ Cuenca, Helmholtz Zentrum Munchen, Univ Med Greifswald, Minist Sante & Hyg Publ, Univ Hosp Dusseldorf, Natl Inst Cardiol, IRL 3189 ESS, Beth Israel Deaconess Med Ctr, Harvard Med Sch, Scuola Super Sant Anna, Univ Latvia, Minist Hlth & Med Serv, Hormozgan Univ Med Sci, Univ Tehran Med Sci, Univ Skovde, Natl Inst Nutr & Food Technol, Univ West Indies, Inst Hosp Mar Invest Med, CIBERCV, Univ Stellenbosch, Univ Duisburg Essen, Karadeniz Tech Univ, Univ Helsinki, Mashhad Univ Med Sci, Rafsanjan Univ Med Sci, Queens Univ Belfast, Tabriz Univ Med Sci, Fasa Univ Med Sci, Shiraz Univ Med Sci, Baqai Med Univ, Ctr Salud Villanueva Norte, Hosp Don Benito Villanueva de la Serena, Univ Insubria, Univ Fed Alagoas, Swiss Trop & Publ Hlth Inst, Univ Basel, Univ Tartu, Univ Sains Malaysia, Umea Univ, Universidade Federal de São Paulo (UNIFESP), Hosp Univ Son Espases, Hosp Clin Porto Alegre, Kindai Univ, Kyoto Univ, I Horbachevsky Ternopil Natl Med Univ, Tel Aviv Univ, Hebrew Univ Jerusalem, Med Univ Warsaw, Jagiellonian Univ Med Coll, Univ Catania, Peking Univ, Wuqu Kawoq, Africa Hlth Res Inst, Univ Geneva, Universidade Federal de Minas Gerais (UFMG), Univ Utrecht, Wageningen Univ, Med Res Fdn, BP Koirala Inst Hlth Sci, Univ Adelaide, Lund Univ, Aristotle Univ Thessaloniki, Inst Natl Sante & Rech Med, Paris Univ, Pontificia Univ Javeriana, PASs Hirszfeld Inst Immunol & Expt Therapy, Univ Agostinho Neto, Univ Politecn Madrid, Int Clin Res Ctr, Ctr Estudios Diabet AC, Univ Autonoma Santo Domingo, Natl Inst Hyg Epidemiol & Microbiol, Inst Clin & Expt Med, Childrens Mem Hlth Inst, Int Hellen Univ, Natl Ctr Cardiovasc Dis, Iceland Heart Assoc, Univ ICESI, Univ Estadual Montes Claros, Kings Coll London, Int Agcy Res Canc, Healis Sekhsaria Inst Publ Hlth, Eternal Heart Care Ctr & Res Inst, Univ Ibadan, Inst Clin Effectiveness & Hlth Policy, Natl Hlth Insurance Serv, Prevent Metab Disorders Res Ctr, Danish Canc Soc Res Ctr, Kermanshah Univ Med Sci, BRAC James P Grant Sch Publ Hlth, Univ Eastern Finland, Beijing Inst Ophthalmol, Universidade Federal de Pernambuco (UFPE), Kyushu Univ, Univ Bergen, Chinese Ctr Dis Control & Prevent, Joep Lange Inst, Chron Dis Res Ctr, Univ Hong Kong, Chinese Univ Hong Kong, Univ Western Australia, French Natl Res Inst Sustainable Dev, Celal Bayar Univ, Fdn Oftalmol Santander, Univ Oran 1, Minist Hlth & Sports, Sante Publ France, Vrije Univ Amsterdam Med Ctr, Amer Univ Beirut, Cairo Univ, Med Univ Varna, Univ Tokyo, Universidade Estadual de Maringá (UEM), Hosp Sick Children, Deakin Univ, Tokyo Metropolitan Inst Gerontol, Hadassah Univ Med Ctr, Norwegian Univ Sci & Technol, Univ Melbourne, Univ Hosp Ctr Zagreb, Heart Fdn, Guangzhou 12th Hosp, Univ Eugenio Maria Hostos, Simon Fraser Univ, Inst Mol & Clin Ophthalmol Basel, WHO Country Off, Guilan Univ Med Sci, Univ Opole, Finnish Inst Hlth & Welf, Univ Ljubljana, Univ Crete, Natl & Kapodistrian Univ Athens, Sree Chitra Tirunal Inst Med Sci & Technol, Harokopio Univ, Maharajgunj Med Campus, Aarhus Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Natl Inst Epidemiol, Univ Munster, Israel Ctr Dis Control, Res Inst Primordial Prevent Noncommunicable Dis, Amsterdam UMC Publ Hlth Res Inst, Kyrgyz State Med Acad, Res Inst Child Nutr, Shahid Beheshti Univ Med Sci, Univ Cambridge, Mazandaran Univ Med Sci, Hypertens Res Ctr, Med Univ Innsbruck, VASCage, Muhimbili Univ Hlth & Allied Sci, Natl Canc Ctr, Univ Coll South Denmark, Oulu Deaconess Inst Fdn, Tartu Univ Clin, Kansai Med Univ, Minist Hlth & Wellness, Univ Groningen, North West Univ, Amrita Inst Med Sci, All India Inst Med Sci, African Populat & Hlth Res Ctr, Minist Salud Publ, Sahlgrens Acad, Endocrinol & Metab Res Ctr, Univ Publ Hlth, Natl Univ Singapore, Tampere Univ Hosp, Tampere Univ, Univ Douala, Univ Cape Town, West Virginia Univ, Oswaldo Cruz Fdn Rene Rachou Res Inst, Shanghai Inst Nutr & Hlth, Taipei Med Univ, Natl Inst Hlth Dev, Univ San Martin de Porres, Consejeria Sanidad Junta Castilla & Leon, Univ Fed Ciencias Saude Porto Alegre, Norrbotten Cty Council, Univ Fed Ouro Preto, Univ Coimbra, Coimbra Univ Hosp Ctr, Inst Neurosci Natl Res Council, Baker Heart & Diabet Inst, Agr Univ Athens, Hosp Israelita Albert Einstein, SB RAS Fed Res Ctr Inst Cytol & Genet, Univ Otago, Univ Padua, Gothenburg Univ, Univ Rijeka, Lausanne Univ Hosp, Univ Lausanne, Escola Nacl Saude Publ Sergio Arouca, Emory Univ, Univ Estadual Centro Oeste, UiT Arctic Univ Norway, ICMR Natl Ctr Dis Informat & Res, Cape Peninsula Univ Technol, Inst Conmemorat Gorgas Estudios Salud, Brown Univ, Univ Edinburgh, Univ Coll Dublin, Inst Nutr Ctr Amer & Panama, Univ Lisbon, Womens Social & Hlth Studies Fdn, Univ Firenze, Ain Shams Univ, Psychiat & Psychol Res Canter, Isfahan Cardiovasc Res Ctr, Strasbourg Univ Hosp, Univ Pecs, Mulago Hosp, Univ Limpopo, Univ Med Sci Cienfuegos, Royal Coll Surgeons Ireland, La Trobe Univ, Int Inst Mol & Cell Biol, Dept Publ Hlth, Univ Brescia, Ludwig Maximilians Univ Munchen, Croatian Inst Publ Hlth, Univ Kebangsaan Malaysia, Bushehr Univ Med Sci, Ulm Univ, Dept Stat, Kobe Univ, Suraj Eye Inst, Natl Inst Hyg & Epidemiol, Univ Med & Pharm Ho Chi Minh City, Natl Hosp Endocrinol, Hanoi Med Univ, LifeDoc Hlth, Univ Turku, Heartfile, Eastern Mediterranean Publ Hlth Network, Univ Manchester, Tachikawa Gen Hosp, Univ Abuja, Korea Ctr Dis Control & Prevent, Japan Wildlife Res Ctr, Istanbul Univ, Univ Fed Parana, Univ Madeira, Univ Novi Sad, Osteoporosis Res Ctr, UniSante, Inst Canc Res Prevent & Clin Network, Inst Clin & Sci Ophthalmol & Acupuncture Jonas, IRCCS Ente Osped Specializzato Gastroenterol S de, Zayed Univ, Catholic Univ Daegu, Jivandeep Hosp, Ctr Invest Saude Angola, Griffith Univ, Natl Dent Care Ctr Singapore, Vietnam Natl Heart Inst, Clin Med Avanzada Dr Abel Gonzalez, Univ Sarajevo, Cardiovasc Prevent Ctr Udine, Publ Hlth Agcy Catalonia, Univ Split, Ardabil Univ Med Sci, London Sch Hyg & Trop Med, Alborz Univ Med Sci, Pure Earth, Univ Putra Malaysia, Univ Malaya, Sotiria Hosp, Univ Valencia, Univ Philippines, Slovak Acad Sci, Univ San Martin Porres, Minas Gerais State Secretariat Hlth, CS S Agustin Ibsalut, Amsterdam Inst Global Hlth & Dev, Univ Nove de Julho, Publ Hlth Agcy Canada, Canarian Hlth Serv, Univ Ind Santander, Assoc Calabrese Epatol, Sahlgrens Univ Hosp, Sitaram Bhartia Inst Sci & Res, Koc Univ, Natl Inst Hlth, Catalan Dept Hlth, South Karelia Social & Hlth Care Dist, German Ctr Cardiovasc Res, McMaster Univ, Hosp Italiano Buenos Aires, Acad Med Ctr Univ Amsterdam, George Inst Global Hlth, Ctr Oral Hlth Serv & Res Mid Norway, Lagos State Univ, Nippon Med Sch, Sungkyunkwan Univ, Shahrekord Univ Med Sci, Finnish Inst Occupat Hlth, Publ Hlth Promot & Dev Org, St Vincents Hosp, Diponegoro Univ, Univ Bari, Inst Reg Sante Publ, Univ Bordeaux, Oslo Metropolitan Univ, Univ Leuven, Univ Bonn, Natl Inst Hyg, Jikei Univ, Fu Jen Catholic Univ, Natl Stat Off, Univ Lincoln, Cent Univ Kerala, Amsterdam Publ Hlth Res Inst, Natl Inst Hlth Res & Dev, Hlth Serv Murcia, Inst Invest Sanitaria Illes Balears, CIBER Epidemiol Salud Publ, Hellen Hlth Fdn, Govt Med Coll, Sefako Makgatho Hlth Sci Univ, Addis Ababa Univ, Israel Def Forces Med Corps, Univ Ctr Occidental Lisandro Alvarado, Univ Tampere, Icahn Sch Med Mt Sinai, Hanoi Univ Publ Hlth, Inst Trop Med, Univ Miguel Hernandez, Univ Lorraine, North Karelia Ctr Publ Hlth, Univ Witwatersrand, Inst Med Res, Capital Med Univ, Xinjiang Med Univ, Shanghai Educ Dev Co Ltd, Orebro Univ, St Georges Univ London, Med Univ Vienna, Komfo Anokye Teaching Hosp, Minist Agr & Rural Affairs, Fudan Univ, Shanghai Educ Dev, Univ Cyprus, Niigata Univ, Iran Univ Med Sci, Ctr Estudios Nutr Infantil, Jiangsu Prov Ctr Dis Control & Prevent, Sun Yat Sen Univ, West Kazakhstan Med Univ, Inner Mongolia Med Univ, Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Universitas Indonesia (UI ), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, University of Helsinki, HUS Helsinki and Uusimaa Hospital District, Department of Public Health, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Eye Centre, Wellcome Trust, Epidemiology, Radiology & Nuclear Medicine, Éco-Anthropologie (EA), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH - Personalized Medicine, Psychiatry, APH - Mental Health, Bin Zhou, Rodrigo M Carrillo-Larco, Goodarz Danaei, Leanne M Riley, Christopher J Paciorek, Gretchen A Stevens, Edward W Gregg, James E Bennett, Bethlehem Solomon, Rosie K Singleton, Marisa K Sophiea, Maria Lc Iurilli, Victor Pf Lhoste, Melanie J Cowan, Stefan Savin, Mark Woodward, Yulia Balanova, Renata Cifkova, Albertino Damasceno, Paul Elliott, Farshad Farzadfar, Jiang He, Nayu Ikeda, Andre P Kengne, Young-Ho Khang, Hyeon Chang Kim, Avula Laxmaiah, Hsien-Ho Lin, Paula Margozzini Maira, J Jaime Miranda, Hannelore Neuhauser, Johan Sundström, Cherian Varghese, Indah S Widyahening, Tomasz Zdrojewski, Leandra Abarca-Gómez, Ziad A Abdeen, Hanan F Abdul Rahim, Niveen M Abu-Rmeileh, Benjamin Acosta-Cazares, Robert J Adams, Wichai Aekplakorn, Kaosar Afsana, Shoaib Afzal, Imelda A Agdeppa, Javad Aghazadeh-Attari, Carlos A Aguilar-Salinas, Charles Agyemang, Noor Ani Ahmad, Ali Ahmadi, Naser Ahmadi, Nastaran Ahmadi, Fariba Ahmadizar, Soheir H Ahmed, Wolfgang Ahrens, Kamel Ajlouni, Rajaa Al-Raddadi, Monira Alarouj, Fadia AlBuhairan, Shahla AlDhukair, Mohamed M Ali, Abdullah Alkandari, Ala'a Alkerwi, Kristine Allin, Eman Aly, Deepak N Amarapurkar, Norbert Amougou, Philippe Amouyel, Lars Bo Andersen, Sigmund A Anderssen, Ranjit Mohan Anjana, Alireza Ansari-Moghaddam, Daniel Ansong, Hajer Aounallah-Skhiri, Joana Araújo, Inger Ariansen, Tahir Aris, Raphael E Arku, Nimmathota Arlappa, Krishna K Aryal, Thor Aspelund, Felix K Assah, Maria Cecília F Assunção, Juha Auvinen, Mária Avdićová, Ana Azevedo, Mohsen Azimi-Nezhad, Fereidoun Azizi, Mehrdad Azmin, Bontha V Babu, Suhad Bahijri, Nagalla Balakrishna, Mohamed Bamoshmoosh, Maciej Banach, Maja Banadinović, Piotr Bandosz, José R Banegas, Joanna Baran, Barbagallo Carlo Maria, Alberto Barceló, Amina Barkat, Marta Barreto, Aluisio Jd Barros, Mauro Virgílio Gomes Barros, Anna Bartosiewicz, Abdul Basit, Joao Luiz D Bastos, Iqbal Bata, Anwar M Batieha, Assembekov Batyrbek, Louise A Baur, Robert Beaglehole, Antonisamy Belavendra, Habiba Ben Romdhane, Mikhail Benet, Lowell S Benson, Salim Berkinbayev, Antonio Bernabe-Ortiz, Gailute Bernotiene, Heloísa Bettiol, Jorge Bezerra, Aroor Bhagyalaxmi, Santosh K Bhargava, Daniel Bia, Katia Biasch, Elysée Claude Bika Lele, Mukharram M Bikbov, Bihungum Bista, Peter Bjerregaard, Espen Bjertness, Marius B Bjertness, Cecilia Björkelund, Katia V Bloch, Anneke Blokstra, Simona Bo, Martin Bobak, Heiner Boeing, Jose G Boggia, Carlos P Boissonnet, Stig E Bojesen, Vanina Bongard, Alice Bonilla-Vargas, Matthias Bopp, Herman Borghs, Pascal Bovet, Christopher B Boyer, Lutgart Braeckman, Imperia Brajkovich, Francesco Branca, Juergen Breckenkamp, Hermann Brenner, Lizzy M Brewster, Yajaira Briceño, Miguel Brito, Graziella Bruno, H Bas Bueno-de-Mesquita, Gloria Bueno, Anna Bugge, Con Burns, Michael Bursztyn, Antonio Cabrera de León, Joseph Cacciottolo, Christine Cameron, Günay Can, Ana Paula C Cândido, Mario V Capanzana, Naděžda Čapková, Eduardo Capuano, Vincenzo Capuano, Viviane C Cardoso, Axel C Carlsson, Joana Carvalho, Felipe F Casanueva, Laura Censi, Marvin Cervantes-Loaiza, Charalambos A Chadjigeorgiou, Snehalatha Chamukuttan, Angelique W Chan, Queenie Chan, Himanshu K Chaturvedi, Nish Chaturvedi, Miao Li Chee, Chien-Jen Chen, Fangfang Chen, Huashuai Chen, Shuohua Chen, Zhengming Chen, Ching-Yu Cheng, Bahman Cheraghian, Imane Cherkaoui Dekkaki, Angela Chetrit, Kuo-Liong Chien, Arnaud Chiolero, Shu-Ti Chiou, Adela Chirita-Emandi, María-Dolores Chirlaque, Belong Cho, Kaare Christensen, Diego G Christofaro, Jerzy Chudek, Eliza Cinteza, Frank Claessens, Janine Clarke, Els Clays, Emmanuel Cohen, Hans Concin, Cyrus Cooper, Tara C Coppinger, Simona Costanzo, Dominique Cottel, Chris Cowell, Cora L Craig, Amelia C Crampin, Ana B Crujeiras, Juan J Cruz, Semánová Csilla, Liufu Cui, Felipe V Cureau, Sarah Cuschieri, Graziella D'Arrigo, Eleonora d'Orsi, Jean Dallongeville, Rachel Dankner, Thomas M Dantoft, Luc Dauchet, Kairat Davletov, Guy De Backer, Dirk De Bacquer, Amalia De Curtis, Giovanni de Gaetano, Stefaan De Henauw, Paula Duarte de Oliveira, David De Ridder, Delphine De Smedt, Mohan Deepa, Alexander D Deev, Vincent Jr DeGennaro, Hélène Delisle, Stefaan Demarest, Elaine Dennison, Valérie Deschamps, Meghnath Dhimal, Augusto F Di Castelnuovo, Juvenal Soares Dias-da-Costa, Alejandro Diaz, Ty T Dickerson, Zivka Dika, Shirin Djalalinia, Ha Tp Do, Annette J Dobson, Chiara Donfrancesco, Silvana P Donoso, Angela Döring, Maria Dorobantu, Marcus Dörr, Kouamelan Doua, Nico Dragano, Wojciech Drygas, Charmaine A Duante, Priscilla Duboz, Rosemary B Duda, Virginija Dulskiene, Anar Dushpanova, Aleksandar Džakula, Vilnis Dzerve, Elzbieta Dziankowska-Zaborszczyk, Ricky Eddie, Ebrahim Eftekhar, Robert Eggertsen, Sareh Eghtesad, Gabriele Eiben, Ulf Ekelund, Mohammad El-Khateeb, Jalila El Ati, Denise Eldemire-Shearer, Marie Eliasen, Roberto Elosua, Rajiv T Erasmus, Raimund Erbel, Cihangir Erem, Louise Eriksen, Johan G Eriksson, Jorge Escobedo-de la Peña, Saeid Eslami, Ali Esmaeili, Alun Evans, David Faeh, Albina A Fakhretdinova, Caroline H Fall, Elnaz Faramarzi, Mojtaba Farjam, Mohammad Reza Fattahi, Asher Fawwad, Francisco J Felix-Redondo, Stephan B Felix, Trevor S Ferguson, Romulo A Fernandes, Daniel Fernández-Bergés, Daniel Ferrante, Thomas Ferrao, Marika Ferrari, Marco M Ferrario, Catterina Ferreccio, Haroldo S Ferreira, Eldridge Ferrer, Jean Ferrieres, Thamara Hubler Figueiró, Günther Fink, Krista Fischer, Leng Huat Foo, Maria Forsner, Heba M Fouad, Damian K Francis, Maria do Carmo Franco, Ruth Frikke-Schmidt, Guillermo Frontera, Flavio D Fuchs, Sandra C Fuchs, Yuki Fujita, Matsuda Fumihiko, Viktoriya Furdela, Ariel Furer, Takuro Furusawa, Zbigniew Gaciong, Andrzej Galbarczyk, Henrike Galenkamp, Fabio Galvano, Jingli Gao, Pei Gao, Manoli Garcia-de-la-Hera, Pablo Garcia, Dickman Gareta, Sarah P Garnett, Jean-Michel Gaspoz, Magda Gasull, Andrea Gazzinelli, Ulrike Gehring, Johanna M Geleijnse, Ronnie George, Ali Ghanbari, Erfan Ghasemi, Oana-Florentina Gheorghe-Fronea, Anup Ghimire, Alessandro Gialluisi, Simona Giampaoli, Christian Gieger, Tiffany K Gill, Jonathan Giovannelli, Glen Gironella, Aleksander Giwercman, Konstantinos Gkiouras, Marcel Goldberg, Rebecca A Goldsmith, Luis F Gomez, Aleksandra Gomula, Helen Gonçalves, Mauer Gonçalves, Bruna Gonçalves Cordeiro da Silva, David A Gonzalez-Chica, Marcela Gonzalez-Gross, Juan P González-Rivas, Clicerio González-Villalpando, María-Elena González-Villalpando, Angel R Gonzalez, Mariano Bonet Gorbea, Frederic Gottrand, Sidsel Graff-Iversen, Dušan Grafnetter, Aneta Grajda, Maria G Grammatikopoulou, Ronald D Gregor, Tomasz Grodzicki, Giuseppe Grosso, Gabriella Gruden, Dongfeng Gu, Ong Peng Guan, Elias F Gudmundsson, Vilmundur Gudnason, Ramiro Guerrero, Idris Guessous, Andre L Guimaraes, Martin C Gulliford, Johanna Gunnlaugsdottir, Marc J Gunter, Prakash C Gupta, Rajeev Gupta, Oye Gureje, Beata Gurzkowska, Laura Gutierrez, Felix Gutzwiller, Seongjun Ha, Farzad Hadaegh, Rosa Haghshenas, Hamid Hakimi, Jytte Halkjær, Ian R Hambleton, Behrooz Hamzeh, Dominique Hange, Abu Am Hanif, Sari Hantunen, Jie Hao, Carla Menêses Hardman, Rachakulla Hari Kumar, Seyed Mohammad Hashemi-Shahri, Jun Hata, Teresa Haugsgjerd, Alison J Hayes, Yuna He, Margit Heier, Marleen Elisabeth Hendriks, Rafael Dos Santos Henrique, Ana Henriques, Leticia Hernandez Cadena, Herqutanto, Sauli Herrala, Ramin Heshmat, Allan G Hill, Sai Yin Ho, Suzanne C Ho, Michael Hobbs, Michelle Holdsworth, Reza Homayounfar, Gonul Horasan Dinc, Andrea Rvr Horimoto, Claudia M Hormiga, Bernardo L Horta, Leila Houti, Christina Howitt, Thein Thein Htay, Aung Soe Htet, Maung Maung Than Htike, Yonghua Hu, José María Huerta, Ilpo Tapani Huhtaniemi, Laetitia Huiart, Martijn Huisman, Abdullatif S Husseini, Inge Huybrechts, Nahla Hwalla, Licia Iacoviello, Anna G Iannone, Mohsen M Ibrahim, Norazizah Ibrahim Wong, M Arfan Ikram, Violeta Iotova, Vilma E Irazola, Takafumi Ishida, Godsent C Isiguzo, Muhammad Islam, Sheikh Mohammed Shariful Islam, Masanori Iwasaki, Rod T Jackson, Jeremy M Jacobs, Hashem Y Jaddou, Tazeen Jafar, Kenneth James, Konrad Jamrozik, Imre Janszky, Edward Janus, Marjo-Riitta Jarvelin, Grazyna Jasienska, Ana Jelaković, Bojan Jelaković, Garry Jennings, Anjani Kumar Jha, Chao Qiang Jiang, Ramon O Jimenez, Karl-Heinz Jöckel, Michel Joffres, Mattias Johansson, Jari J Jokelainen, Jost B Jonas, Torben Jørgensen, Pradeep Joshi, Farahnaz Joukar, Jacek Jóżwiak, Anne Juolevi, Gregor Jurak, Vesna Jureša, Rudolf Kaaks, Anthony Kafatos, Eero O Kajantie, Zhanna Kalmatayeva, Natasa Kalpourtzi, Ofra Kalter-Leibovici, Freja B Kampmann, Srinivasan Kannan, Eva Karaglani, Line L Kårhus, Khem B Karki, Marzieh Katibeh, Joanne Katz, Jussi Kauhanen, Prabhdeep Kaur, Maryam Kavousi, Gyulli M Kazakbaeva, Ulrich Keil, Lital Keinan Boker, Sirkka Keinänen-Kiukaanniemi, Roya Kelishadi, Han Cg Kemper, Maryam Keramati, Alina Kerimkulova, Mathilde Kersting, Timothy Key, Yousef Saleh Khader, Davood Khalili, Kay-Tee Khaw, Bahareh Kheiri, Motahareh Kheradmand, Alireza Khosravi, Ursula Kiechl-Kohlendorfer, Stefan Kiechl, Japhet Killewo, Dong Wook Kim, Jeongseon Kim, Heidi Klakk, Magdalena Klimek, Jurate Klumbiene, Michael Knoflach, Elin Kolle, Patrick Kolsteren, Jukka P Kontto, Raija Korpelainen, Paul Korrovits, Jelena Kos, Seppo Koskinen, Katsuyasu Kouda, Sudhir Kowlessur, Slawomir Koziel, Jana Kratenova, Vilma Kriaucioniene, Peter Lund Kristensen, Steiner Krokstad, Daan Kromhout, Herculina S Kruger, Ruzena Kubinova, Renata Kuciene, Urho M Kujala, Zbigniew Kulaga, R Krishna Kumar, Pawel Kurjata, Yadlapalli S Kusuma, Vladimir Kutsenko, Kari Kuulasmaa, Catherine Kyobutungi, Tiina Laatikainen, Carl Lachat, Youcef Laid, Tai Hing Lam, Orlando Landrove, Vera Lanska, Georg Lappas, Bagher Larijani, Tint Swe Latt, Gwenaëlle Le Coroller, Khanh Le Nguyen Bao, Tuyen D Le, Jeannette Lee, Jeonghee Lee, Nils Lehmann, Terho Lehtimäki, Daniel Lemogoum, Naomi S Levitt, Yanping Li, Christa L Lilly, Wei-Yen Lim, M Fernanda Lima-Costa, Xu Lin, Yi-Ting Lin, Lars Lind, Vijaya Lingam, Allan Linneberg, Lauren Lissner, Mieczyslaw Litwin, Wei-Cheng Lo, Helle-Mai Loit, Esther Lopez-Garcia, Tania Lopez, Paulo A Lotufo, José Eugenio Lozano, Iva Lukačević Lovrenčić, Janice L Lukrafka, Dalia Luksiene, Annamari Lundqvist, Robert Lundqvist, Nuno Lunet, Michala Lustigová, Edyta Luszczki, Guansheng Ma, Jun Ma, George Ll Machado-Coelho, Aristides M Machado-Rodrigues, Enguerran Macia, Luisa M Macieira, Ahmed A Madar, Stefania Maggi, Dianna J Magliano, Emmanuella Magriplis, Gowri Mahasampath, Bernard Maire, Marjeta Majer, Marcia Makdisse, Fatemeh Malekzadeh, Reza Malekzadeh, Rahul Malhotra, Kodavanti Mallikharjuna Rao, Sofia K Malyutina, Lynell V Maniego, Yannis Manios, Jim I Mann, Fariborz Mansour-Ghanaei, Enzo Manzato, Anie Marcil, Staffan B Mårild, Mihalea Marinović Glavić, Pedro Marques-Vidal, Larissa Pruner Marques, Jaume Marrugat, Reynaldo Martorell, Luis P Mascarenhas, Marija Matasin, Ellisiv B Mathiesen, Prashant Mathur, Alicia Matijasevich, Piotr Matlosz, Tandi E Matsha, Christina Mavrogianni, Jean Claude N Mbanya, Anselmo J Mc Donald Posso, Shelly R McFarlane, Stephen T McGarvey, Stela McLachlan, Rachael M McLean, Scott B McLean, Breige A McNulty, Sounnia Mediene Benchekor, Jurate Medzioniene, Parinaz Mehdipour, Kirsten Mehlig, Amir Houshang Mehrparvar, Aline Meirhaeghe, Christa Meisinger, Carlos Mendoza Montano, Ana Maria B Menezes, Geetha R Menon, Alibek Mereke, Indrapal I Meshram, Andres Metspalu, Haakon E Meyer, Jie Mi, Nathalie Michels, Kairit Mikkel, Karolina Milkowska, Jody C Miller, Cláudia S Minderico, G K Mini, Mohammad Reza Mirjalili, Erkin Mirrakhimov, Marjeta Mišigoj-Duraković, Pietro A Modesti, Sahar Saeedi Moghaddam, Bahram Mohajer, Mostafa K Mohamed, Shukri F Mohamed, Kazem Mohammad, Mohammad Reza Mohammadi, Zahra Mohammadi, Noushin Mohammadifard, Reza Mohammadpourhodki, Viswanathan Mohan, Salim Mohanna, Muhammad Fadhli Mohd Yusoff, Iraj Mohebbi, Farnam Mohebi, Marie Moitry, Line T Møllehave, Dénes Molnár, Amirabbas Momenan, Charles K Mondo, Eric Monterrubio-Flores, Kotsedi Daniel K Monyeki, Jin Soo Moon, Mahmood Moosazadeh, Leila B Moreira, Alain Morejon, Luis A Moreno, Karen Morgan, George Moschonis, Malgorzata Mossakowska, Aya Mostafa, Seyed-Ali Mostafavi, Jorge Mota, Mohammad Esmaeel Motlagh, Jorge Motta, Marcos André Moura-Dos-Santos, Malay K Mridha, Kelias P Msyamboza, Thet Thet Mu, Alfa J Muhihi, Maria L Muiesan, Martina Müller-Nurasyid, Neil Murphy, Jaakko Mursu, Kamarul Imran Musa, Sanja Musić Milanović, Vera Musil, Norlaila Mustafa, Iraj Nabipour, Shohreh Naderimagham, Gabriele Nagel, Balkish M Naidu, Farid Najafi, Harunobu Nakamura, Jana Námešná, Ei Ei K Nang, Vinay B Nangia, Sameer Narake, Ndeye Coumba Ndiaye, William A Neal, Azim Nejatizadeh, Ilona Nenko, Martin Neovius, Chung T Nguyen, Nguyen D Nguyen, Quang V Nguyen, Quang Ngoc Nguyen, Ramfis E Nieto-Martínez, Teemu J Niiranen, Yury P Nikitin, Toshiharu Ninomiya, Sania Nishtar, Marina A Njelekela, Marianna Noale, Oscar A Noboa, Ahmad Ali Noorbala, Teresa Norat, Maria Nordendahl, Børge G Nordestgaard, Noto Davide, Natalia Nowak-Szczepanska, Mohannad Al Nsour, Baltazar Nunes, Terence W O'Neill, Dermot O'Reilly, Caleb Ochimana, Eiji Oda, Augustine N Odili, Kyungwon Oh, Kumiko Ohara, Ryutaro Ohtsuka, Valérie Olié, Maria Teresa A Olinto, Isabel O Oliveira, Mohd Azahadi Omar, Altan Onat, Sok King Ong, Lariane M Ono, Pedro Ordunez, Rui Ornelas, Pedro J Ortiz, Clive Osmond, Sergej M Ostojic, Afshin Ostovar, Johanna A Otero, Kim Overvad, Ellis Owusu-Dabo, Fred Michel Paccaud, Cristina Padez, Elena Pahomova, Karina Mary de Paiva, Andrzej Pająk, Domenico Palli, Luigi Palmieri, Wen-Harn Pan, Songhomitra Panda-Jonas, Francesco Panza, Mariela Paoli, Dimitrios Papandreou, Soon-Woo Park, Suyeon Park, Winsome R Parnell, Mahboubeh Parsaeian, Patrick Pasquet, Nikhil D Patel, Halyna Pavlyshyn, Ivan Pećin, Mangesh S Pednekar, João M Pedro, Nasheeta Peer, Sergio Viana Peixoto, Markku Peltonen, Alexandre C Pereira, Karen Gda Peres, Marco A Peres, Annette Peters, Janina Petkeviciene, Niloofar Peykari, Son Thai Pham, Rafael N Pichardo, Iris Pigeot, Hynek Pikhart, Aida Pilav, Lorenza Pilotto, Freda Pitakaka, Aleksandra Piwonska, Andreia N Pizarro, Pedro Plans-Rubió, Ozren Polašek, Miquel Porta, Anil Poudyal, Farhad Pourfarzi, Akram Pourshams, Hossein Poustchi, Rajendra Pradeepa, Alison J Price, Jacqueline F Price, Rui Providencia, Soile E Puhakka, Maria Puiu, Margus Punab, Radwan F Qasrawi, Mostafa Qorbani, Daniel Queiroz, Tran Quoc Bao, Ivana Radić, Ricardas Radisauskas, Salar Rahimikazerooni, Mahfuzar Rahman, Olli Raitakari, Manu Raj, Ellina M Rakhimova, Sudha Ramachandra Rao, Ambady Ramachandran, Elisabete Ramos, Lekhraj Rampal, Sanjay Rampal, Daniel A Rangel Reina, Vayia Rarra, Cassiano Ricardo Rech, Josep Redon, Paul Ferdinand M Reganit, Valéria Regecová, Luis Revilla, Abbas Rezaianzadeh, Robespierre Ribeiro, Elio Riboli, Adrian Richter, Fernando Rigo, Tobias F Rinke de Wit, Raphael M Ritti-Dias, Cynthia Robitaille, Fernando Rodríguez-Artalejo, María Del Cristo Rodriguez-Perez, Laura A Rodríguez-Villamizar, Ulla Roggenbuck, Rosalba Rojas-Martinez, Dora Romaguera, Elisabetta L Romeo, Annika Rosengren, Joel Gr Roy, Adolfo Rubinstein, Jean-Bernard Ruidavets, Blanca Sandra Ruiz-Betancourt, Maria Ruiz-Castell, Iuliia A Rusakova, Paola Russo, Marcin Rutkowski, Charumathi Sabanayagam, Hamideh Sabbaghi, Harshpal S Sachdev, Alireza Sadjadi, Ali Reza Safarpour, Sare Safi, Saeid Safiri, Olfa Saidi, Sibel Sakarya, Nader Saki, Benoit Salanave, Eduardo Salazar Martinez, Diego Salmerón, Veikko Salomaa, Jukka T Salonen, Massimo Salvetti, Jose Sánchez-Abanto, Susana Sans, Diana A Santos, Ina S Santos, Lèlita C Santos, Maria Paula Santos, Rute Santos, Jouko L Saramies, Luis B Sardinha, Giselle Sarganas, Nizal Sarrafzadegan, Thirunavukkarasu Sathish, Kai-Uwe Saum, Savvas Savva, Norie Sawada, Mariana Sbaraini, Marcia Scazufca, Beatriz D Schaan, Herman Schargrodsky, Sabine Schipf, Carsten O Schmidt, Peter Schnohr, Ben Schöttker, Sara Schramm, Constance Schultsz, Aletta E Schutte, Sylvain Sebert, Aye Aye Sein, Abhijit Sen, Idowu O Senbanjo, Sadaf G Sepanlou, Jennifer Servais, Svetlana A Shalnova, Teresa Shamah-Levy, Morteza Shamshirgaran, Coimbatore Subramaniam Shanthirani, Maryam Sharafkhah, Sanjib K Sharma, Jonathan E Shaw, Amaneh Shayanrad, Ali Akbar Shayesteh, Zumin Shi, Kenji Shibuya, Hana Shimizu-Furusawa, Dong Wook Shin, Majid Shirani, Rahman Shiri, Namuna Shrestha, Khairil Si-Ramlee, Alfonso Siani, Rosalynn Siantar, Abla M Sibai, Caroline Ramos de Moura Silva, Diego Augusto Santos Silva, Mary Simon, Judith Simons, Leon A Simons, Michael Sjöström, Jolanta Slowikowska-Hilczer, Przemyslaw Slusarczyk, Liam Smeeth, Hung-Kwan So, Fernanda Cunha Soares, Eugène Sobngwi, Stefan Söderberg, Agustinus Soemantri, Reecha Sofat, Vincenzo Solfrizzi, Mohammad Hossein Somi, Emily Sonestedt, Yi Song, Thorkild Ia Sørensen, Elin P Sørgjerd, Maroje Sorić, Charles Sossa Jérome, Aïcha Soumaré, Bente Sparboe-Nilsen, Karen Sparrenberger, Jan A Staessen, Gregor Starc, Bill Stavreski, Jostein Steene-Johannessen, Peter Stehle, Aryeh D Stein, George S Stergiou, Jochanan Stessman, Jutta Stieber, Doris Stöckl, Tanja Stocks, Jakub Stokwiszewski, Karien Stronks, Maria Wany Strufaldi, Machi Suka, Chien-An Sun, Yn-Tz Sung, Paibul Suriyawongpaisal, Rody G Sy, Holly E Syddall, René Charles Sylva, Moyses Szklo, E Shyong Tai, Mari-Liis Tammesoo, Abdonas Tamosiunas, Eng Joo Tan, Xun Tang, Frank Tanser, Yong Tao, Mohammed Rasoul Tarawneh, Carolina B Tarqui-Mamani, Anne Taylor, Julie Taylor, William R Tebar, Grethe S Tell, Tania Tello, Yih Chung Tham, K R Thankappan, Holger Theobald, Xenophon Theodoridis, Lutgarde Thijs, Mikael Thinggaard, Nihal Thomas, Barbara Thorand, Betina H Thuesen, Erik J Timmermans, Dwi H Tjandrarini, Anne Tjonneland, Ulla Toft, Hanna K Tolonen, Janne S Tolstrup, Murat Topbas, Roman Topór-Madry, María José Tormo, Michael J Tornaritis, Maties Torrent, Laura Torres-Collado, Giota Touloumi, Pierre Traissac, Areti Triantafyllou, Dimitrios Trichopoulos, Antonia Trichopoulou, Oanh Th Trinh, Atul Trivedi, Lechaba Tshepo, Shoichiro Tsugane, Azaliia M Tuliakova, Marshall K Tulloch-Reid, Fikru Tullu, Tomi-Pekka Tuomainen, Jaakko Tuomilehto, Maria L Turley, Gilad Twig, Per Tynelius, Christophe Tzourio, Peter Ueda, Eunice Ugel, Hanno Ulmer, Hannu Mt Uusitalo, Gonzalo Valdivia, Damaskini Valvi, Rob M van Dam, Bert-Jan van den Born, Johan Van der Heyden, Yvonne T van der Schouw, Koen Van Herck, Hoang Van Minh, Natasja M Van Schoor, Irene Gm van Valkengoed, Elisabeth M van Zutphen, Dirk Vanderschueren, Diego Vanuzzo, Anette Varbo, Senthil K Vasan, Tomas Vega, Toomas Veidebaum, Gustavo Velasquez-Melendez, Giovanni Veronesi, Wm Monique Verschuren, Roosmarijn Verstraeten, Cesar G Victora, Lucie Viet, Salvador Villalpando, Paolo Vineis, Jesus Vioque, Jyrki K Virtanen, Sophie Visvikis-Siest, Bharathi Viswanathan, Tiina Vlasoff, Peter Vollenweider, Ari Voutilainen, Alisha N Wade, Janette Walton, Elvis Oa Wambiya, Wan Mohamad Wan Bebakar, Wan Nazaimoon Wan Mohamud, Rildo de Souza Wanderley Júnior, Ming-Dong Wang, Ningli Wang, Qian Wang, Xiangjun Wang, Ya Xing Wang, Ying-Wei Wang, S Goya Wannamethee, Nicholas Wareham, Wenbin Wei, Aneta Weres, Bo Werner, Peter H Whincup, Kurt Widhalm, Andrzej Wiecek, Rainford J Wilks, Johann Willeit, Peter Willeit, Emmanuel A Williams, Tom Wilsgaard, Bogdan Wojtyniak, Roy A Wong-McClure, Andrew Wong, Tien Yin Wong, Jean Woo, Frederick C Wu, Shouling Wu, Justyna Wyszynska, Haiquan Xu, Liang Xu, Nor Azwany Yaacob, Weili Yan, Ling Yang, Xiaoguang Yang, Yang Yang, Tabara Yasuharu, Xingwang Ye, Panayiotis K Yiallouros, Moein Yoosefi, Akihiro Yoshihara, San-Lin You, Novie O Younger-Coleman, Ahmad Faudzi Yusoff, Ahmad A Zainuddin, Seyed Rasoul Zakavi, Farhad Zamani, Sabina Zambon, Antonis Zampelas, Maria Elisa Zapata, Ko Ko Zaw, Kristyna Zejglicova, Tajana Zeljkovic Vrkic, Yi Zeng, Luxia Zhang, Zhen-Yu Zhang, Dong Zhao, Ming-Hui Zhao, Shiqi Zhen, Yingfeng Zheng, Bekbolat Zholdin, Dan Zhu, Marie Zins, Emanuel Zitt, Yanina Zocalo, Nada Zoghlami, Julio Zuñiga Cisneros, Majid Ezzati, Sakarya, Sibel (ORCID 0000-0002-9959-6240 & YÖK ID 172028), Zhou, Bin, Carrillo-Larco, Rodrigo M., Danaei, Goodarz, Riley, Leanne M., Paciorek, Christopher J., Stevens, Gretchen A., Gregg, Edward W., Bennett, James E., Solomon, Bethlehem, Singleton, Rosie K., Sophiea, Marisa K., Iurilli, Maria L. C., Lhoste, Victor P. F., Cowan, Melanie J., Savin, Stefan, Woodward, Mark, Balanova, Yulia, Cifkova, Renata, Damasceno, Albertino, Elliott, Paul, Farzadfar, Farshad, He, Jiang, Ikeda, Nayu, Kengne, Andre P., Khang, Young-Ho, Kim, Hyeon Chang, Laxmaiah, Avula, Lin, Hsien-Ho, Margozzini Maira, Paula, Miranda, J. Jaime, Neuhauser, Hannelore, Sundstrom, Johan, Varghese, Cherian, Widyahening, Indah S., Zdrojewski, Tomasz, Ezzati, Majid, Abarca-Gomez, Leandra, Abdeen, Ziad A., Rahim, Hanan F. Abdul, Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert J., Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A., Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmadi, Nastaran, Ahmadizar, Fariba, Ahmed, Soheir H., Ahrens, Wolfgang, Ajlouni, Kamel, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M., Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Aly, Eman, Amarapurkar, Deepak N., Amougou, Norbert, Amouyel, Philippe, Andersen, Lars Bo, Anderssen, Sigmund A., Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Ansong, Daniel, Aounallah-Skhiri, Hajer, Araujo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E., Arlappa, Nimmathota, Aryal, Krishna K., Aspelund, Thor, Assah, Felix K., Assuncao, Maria Cecilia F., Auvinen, Juha, Avdicova, Maria, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V., Bahijri, Suhad, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Banadinovic, Maja, Bandosz, Piotr, Banegas, Jose R., Baran, Joanna, Barbagallo, Carlo M., Barcelo, Alberto, Barkat, Amina, Barreto, Marta, Barros, Aluisio J. D., Gomes Barros, Mauro Virgilio, Bartosiewicz, Anna, Basit, Abdul, Bastos, Joao Luiz D., Bata, Iqbal, Batieha, Anwar M., Batyrbek, Assembekov, Baur, Louise A., Beaglehole, Robert, Belavendra, Antonisamy, Ben Romdhane, Habiba, Benet, Mikhail, Benson, Lowell S., Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bettiol, Heloisa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bhargava, Santosh K., Bia, Daniel, Biasch, Katia, Lele, Elysee Claude Bika, Bikbov, Mukharram M., Bista, Bihungum, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Bjorkelund, Cecilia, Bloch, Katia V., Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boeing, Heiner, Boggia, Jose G., Boissonnet, Carlos P., Bojesen, Stig E., Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthias, Bovet, Pascal, Boyer, Christopher B., Braeckman, Lutgart, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M., Briceno, Yajaira, Brito, Miguel, Bruno, Graziella, Bueno-de-Mesquita, H. Bas, Bueno, Gloria, Bugge, Anna, Burns, Con, Bursztyn, Michael, Cabrera de Leon, Antonio, Cacciottolo, Joseph, Cameron, Christine, Can, Gunay, Candido, Ana Paula C., Capanzana, Mario V., Capkova, Nadezda, Capuano, Eduardo, Capuano, Vincenzo, Cardoso, Viviane C., Carlsson, Axel C., Carvalho, Joana, Casanueva, Felipe F., Censi, Laura, Cervantes-Loaiza, Marvin, Chadjigeorgiou, Charalambos A., Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nish, Chee, Miao Li, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheraghian, Bahman, Dekkaki, Imane Cherkaoui, Chetrit, Angela, Chien, Kuo-Liong, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Chirlaque, Maria-Dolores, Cho, Belong, Christensen, Kaare, Christofaro, Diego G., Chudek, Jerzy, Cinteza, Eliza, Clarke, Janine, Clays, Els, Cohen, Emmanuel, Concin, Hans, Cooper, Cyrus, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crampin, Amelia C., Crujeiras, Ana B., Cruz, Juan J., Csilla, Semanova, Cui, Liufu, Cureau, Felipe V., Cuschieri, Sarah, D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Dankner, Rachel, Dantoft, Thomas M., Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, De Curtis, Amalia, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, David, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D., DeGennaro, Vincent Jr, Delisle, Helene, Demarest, Stefaan, Dennison, Elaine, Deschamps, Valerie, Dhimal, Meghnath, Di Castelnuovo, Augusto F., Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Dickerson, Ty T., Dika, Zivka, Djalalinia, Shirin, Do, Ha T. P., Dobson, Annette J., Donfrancesco, Chiara, Donoso, Silvana P., Doering, Angela, Dorobantu, Maria, Doerr, Marcus, Doua, Kouamelan, Dragano, Nico, Drygas, Wojciech, Duante, Charmaine A., Duboz, Priscilla, Duda, Rosemary B., Dulskiene, Virginija, Dushpanova, Anar, Dzakula, Aleksandar, Dzerve, Vilnis, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Eftekhar, Ebrahim, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elosua, Roberto, Erasmus, Rajiv T., Erbel, Raimund, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G., Escobedo-de la Pena, Jorge, Eslami, Saeid, Esmaeili, Ali, Evans, Alun, Faeh, David, Fakhretdinova, Albina A., Fall, Caroline H., Faramarzi, Elnaz, Farjam, Mojtaba, Fattahi, Mohammad Reza, Fawwad, Asher, Felix-Redondo, Francisco J., Felix, Stephan B., Ferguson, Trevor S., Fernandes, Romulo A., Fernandez-Berges, Daniel, Ferrante, Daniel, Ferrao, Thomas, Ferrari, Marika, Ferrario, Marco M., Ferreccio, Catterina, Ferreira, Haroldo S., Ferrer, Eldridge, Ferrieres, Jean, Figueiro, Thamara Hubler, Fink, Gunther, Fischer, Krista, Foo, Leng Huat, Forsner, Maria, Fouad, Heba M., Francis, Damian K., Franco, Maria do Carmo, Frikke-Schmidt, Ruth, Frontera, Guillermo, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Fumihiko, Matsuda, Furdela, Viktoriya, Furer, Ariel, Furusawa, Takuro, Gaciong, Zbigniew, Galbarczyk, Andrzej, Galenkamp, Henrike, Galvano, Fabio, Gao, Jingli, Gao, Pei, Garcia-de-la-Hera, Manoli, Garcia, Pablo, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gazzinelli, Andrea, Gehring, Ulrike, Geleijnse, Johanna M., George, Ronnie, Ghanbari, Ali, Ghasemi, Erfan, Gheorghe-Fronea, Oana-Florentina, Ghimire, Anup, Gialluisi, Alessandro, Giampaoli, Simona, Gieger, Christian, Gill, Tiffany K., Giovannelli, Jonathan, Gironella, Glen, Giwercman, Aleksander, Gkiouras, Konstantinos, Goldberg, Marcel, Goldsmith, Rebecca A., Gomez, Luis F., Gomula, Aleksandra, Cordeiro da Silva, Bruna Goncalves, Goncalves, Helen, Goncalves, Mauer, Gonzalez-Chica, David A., Gonzalez-Gross, Marcela, Gonzalez-Rivas, Juan P., Gonzalez-Villalpando, Clicerio, Gonzalez-Villalpando, Maria-Elena, Gonzalez, Angel R., Bonet Gorbea, Mariano, Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dusan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grosso, Giuseppe, Gruden, Gabriella, Gu, Dongfeng, Guan, Ong Peng, Gudmundsson, Elias F., Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Gunter, Marc J., Gupta, Prakash C., Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Ha, Seongjun, Hadaegh, Farzad, Haghshenas, Rosa, Hakimi, Hamid, Halkjaer, Jytte, Hambleton, Ian R., Hamzeh, Behrooz, Hange, Dominique, Hanif, Abu A. M., Hantunen, Sari, Hao, Jie, Hardman, Carla Meneses, Kumar, Rachakulla Hari, Hashemi-Shahri, Seyed Mohammad, Hata, Jun, Haugsgjerd, Teresa, Hayes, Alison J., He, Yuna, Heier, Margit, Hendriks, Marleen Elisabeth, Henrique, Rafael dos Santos, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Heshmat, Ramin, Hill, Allan G., Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Holdsworth, Michelle, Homayounfar, Reza, Dinc, Gonul Horasan, Horimoto, Andrea R. V. R., Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, Jose Maria, Huhtaniemi, Ilpo Tapani, Huiart, Laetitia, Huisman, Martijn, Husseini, Abdullatif S., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Wong, Norazizah Ibrahim, Ikram, M. Arfan, Iotova, Violeta, Irazola, Vilma E., Ishida, Takafumi, Isiguzo, Godsent C., Islam, Muhammad, Islam, Sheikh Mohammed Shariful, Iwasaki, Masanori, Jackson, Rod T., Jacobs, Jeremy M., Jaddou, Hashem Y., Jafar, Tazeen, James, Kenneth, Jamrozik, Konrad, Janszky, Imre, Janus, Edward, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jelakovic, Ana, Jelakovic, Bojan, Jennings, Garry, Jha, Anjani Kumar, Jiang, Chao Qiang, Jimenez, Ramon O., Joeckel, Karl-Heinz, Joffres, Michel, Johansson, Mattias, Jokelainen, Jari J., Jonas, Jost B., Jorgensen, Torben, Joshi, Pradeep, Joukar, Farahnaz, Jozwiak, Jacek, Juolevi, Anne, Jurak, Gregor, Juresa, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kajantie, Eero O., Kalmatayeva, Zhanna, Kalpourtzi, Natasa, Kalter-Leibovici, Ofra, Kampmann, Freja B., Kannan, Srinivasan, Karaglani, Eva, Karhus, Line L., Karki, Khem B., Katibeh, Marzieh, Katz, Joanne, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli M., Keil, Ulrich, Boker, Lital Keinan, Keinanen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kemper, Han C. G., Keramati, Maryam, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khaw, Kay-Tee, Kheiri, Bahareh, Kheradmand, Motahareh, Khosravi, Alireza, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Dong Wook, Kim, Jeongseon, Klakk, Heidi, Klimek, Magdalena, Klumbiene, Jurate, Knoflach, Michael, Kolle, Elin, Kolsteren, Patrick, Kontto, Jukka P., Korpelainen, Raija, Korrovits, Paul, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kowlessur, Sudhir, Koziel, Slawomir, Kratenova, Jana, Kriaucioniene, Vilma, Kristensen, Peter Lund, Krokstad, Steiner, Kromhout, Daan, Kruger, Herculina S., Kubinova, Ruzena, Kuciene, Renata, Kujala, Urho M., Kulaga, Zbigniew, Kumar, R. Krishna, Kurjata, Pawel, Kusuma, Yadlapalli S., Kutsenko, Vladimir, Kuulasmaa, Kari, Kyobutungi, Catherine, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Latt, Tint Swe, Le Coroller, Gwenaelle, Khanh Le Nguyen Bao, Le, Tuyen D., Lee, Jeannette, Lee, Jeonghee, Lehmann, Nils, Lehtimaki, Terho, Lemogoum, Daniel, Levitt, Naomi S., Li, Yanping, Lilly, Christa L., Lim, Wei-Yen, Lima-Costa, M. Fernanda, Lin, Xu, Lin, Yi-Ting, Lind, Lars, Lingam, Vijaya, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Lo, Wei-Cheng, Loit, Helle-Mai, Lopez-Garcia, Esther, Lopez, Tania, Lotufo, Paulo A., Lozano, Jose Eugenio, Lovrencic, Iva Lukacevic, Lukrafka, Janice L., Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lunet, Nuno, Lustigova, Michala, Luszczki, Edyta, Ma, Guansheng, Ma, Jun, Machado-Coelho, George L. L., Machado-Rodrigues, Aristides M., Macia, Enguerran, Macieira, Luisa M., Madar, Ahmed A., Maggi, Stefania, Magliano, Dianna J., Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Mallikharjuna, Kodavanti, Malyutina, Sofia K., Maniego, Lynell V., Manios, Yannis, Mann, Jim I., Mansour-Ghanaei, Fariborz, Manzato, Enzo, Marcil, Anie, Margozzini, Paula, Marild, Staffan B., Glavic, Mihalea Marinovic, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martorell, Reynaldo, Mascarenhas, Luis P., Matasin, Marija, Mathiesen, Ellisiv B., Mathur, Prashant, Matijasevich, Alicia, Matlosz, Piotr, Matsha, Tandi E., Mavrogianni, Christina, Mbanya, Jean Claude N., Mc Donald Posso, Anselmo J., McFarlane, Shelly R., McGarvey, Stephen T., McLachlan, Stela, McLean, Rachael M., McLean, Scott B., McNulty, Breige A., Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisinger, Christa, Mendoza Montano, Carlos, Menezes, Ana Maria B., Menon, Geetha R., Mereke, Alibek, Meshram, Indrapal I., Metspalu, Andres, Meyer, Haakon E., Mi, Jie, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C., Minderico, Claudia S., Mini, G. K., Mirjalili, Mohammad Reza, Mirrakhimov, Erkin, Misigoj-Durakovic, Marjeta, Modesti, Pietro A., Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K., Mohamed, Shukri F., Mohammad, Kazem, Mohammadi, Mohammad Reza, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Mollehave, Line T., Molnar, Denes, Momenan, Amirabbas, Mondo, Charles K., Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K., Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mostafavi, Seyed-Ali, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Andre Moura-dos-Santos, Marcos, Mridha, Malay K., Msyamboza, Kelias P., Mu, Thet Thet, Muhihi, Alfa J., Muiesan, Maria L., Muller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M., Najafi, Farid, Nakamura, Harunobu, Namesna, Jana, Nang, Ei Ei K., Nangia, Vinay B., Narake, Sameer, Ndiaye, Ndeye Coumba, Neal, William A., Nejatizadeh, Azim, Nenko, Ilona, Neovius, Martin, Neuhauser, Hannelore K., Nguyen, Chung T., Nguyen, Nguyen D., Nguyen, Quang V., Quang Ngoc Nguyen, Nieto-Martinez, Ramfis E., Niiranen, Teemu J., Nikitin, Yury P., Ninomiya, Toshiharu, Nishtar, Sania, Njelekela, Marina A., Noale, Marianna, Noboa, Oscar A., Noorbala, Ahmad Ali, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Borge G., Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nunes, Baltazar, O'Neill, Terence W., O'Reilly, Dermot, Ochimana, Caleb, Oda, Eiji, Odili, Augustine N., Oh, Kyungwon, Ohara, Kumiko, Ohtsuka, Ryutaro, Olie, Valerie, Olinto, Maria Teresa A., Oliveira, Isabel O., Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M., Ordunez, Pedro, Ornelas, Rui, Ortiz, Pedro J., Osmond, Clive, Ostojic, Sergej M., Ostovar, Afshin, Otero, Johanna A., Overvad, Kim, Owusu-Dabo, Ellis, Paccaud, Fred Michel, Padez, Cristina, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Panza, Francesco, Paoli, Mariela, Papandreou, Dimitrios, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R., Parsaeian, Mahboubeh, Pasquet, Patrick, Patel, Nikhil D., Pavlyshyn, Halyna, Pecin, Ivan, Pednekar, Mangesh S., Pedro, Joao M., Peer, Nasheeta, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C., Peres, Karen G. D. A., Peres, Marco A., Peters, Annette, Petkeviciene, Janina, Peykari, Niloofar, Son Thai Pham, Pichardo, Rafael N., Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N., Plans-Rubio, Pedro, Polasek, Ozren, Porta, Miquel, Poudyal, Anil, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J., Price, Jacqueline F., Providencia, Rui, Puhakka, Soile E., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Queiroz, Daniel, Tran Quoc Bao, Radic, Ivana, Radisauskas, Ricardas, Rahimikazerooni, Salar, Rahman, Mahfuzar, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina M., Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramos, Elisabete, Rampal, Lekhraj, Rampal, Sanjay, Rangel Reina, Daniel A., Rarra, Vayia, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M., Regecova, Valeria, Revilla, Luis, Rezaianzadeh, Abbas, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, de Wit, Tobias F. Rinke, Ritti-Dias, Raphael M., Robitaille, Cynthia, Rodriguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, Maria, Rodriguez-Villamizar, Laura A., Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Romaguera, Dora, Romeo, Elisabetta L., Rosengren, Annika, Roy, Joel G. R., Rubinstein, Adolfo, Ruidavets, Jean-Bernard, Sandra Ruiz-Betancourt, Blanca, Ruiz-Castell, Maria, Rusakova, Iuliia A., Russo, Paola, Rutkowski, Marcin, Sabanayagam, Charumathi, Sabbaghi, Hamideh, Sachdev, Harshpal S., Sadjadi, Alireza, Safarpour, Ali Reza, Safi, Sare, Safiri, Saeid, Saidi, Olfa, Saki, Nader, Salanave, Benoit, Salazar Martinez, Eduardo, Salmeron, Diego, Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sanchez-Abanto, Jose, Sans, Susana, Santos, Diana A., Santos, Ina S., Santos, Lelita C., Santos, Maria Paula, Santos, Rute, Saramies, Jouko L., Sardinha, Luis B., Sarganas, Giselle, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savvas, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D., Schargrodsky, Herman, Schipf, Sabine, Schmidt, Carsten O., Schnohr, Peter, Schoettker, Ben, Schramm, Sara, Schultsz, Constance, Schutte, Aletta E., Sebert, Sylvain, Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Servais, Jennifer, Shalnova, Svetlana A., Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K., Shaw, Jonathan E., Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M., de Moura Silva, Caroline Ramos, Santos Silva, Diego Augusto, Simon, Mary, Simons, Judith, Simons, Leon A., Sjostrom, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobngwi, Eugene, Soderberg, Stefan, Soemantri, Agustinus, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sorensen, Thorkild I. A., Sorgjerd, Elin P., Soric, Maroje, Jerome, Charles Sossa, Soumare, Aicha, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Staessen, Jan A., Starc, Gregor, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stoeckl, Doris, Stocks, Tanja, Stokwiszewski, Jakub, Stronks, Karien, Strufaldi, Maria Wany, Suka, Machi, Sun, Chien-An, Sung, Yn-Tz, Suriyawongpaisal, Paibul, Sy, Rody G., Syddall, Holly E., Sylva, Rene Charles, Szklo, Moyses, Tai, E. Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tan, Eng Joo, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarqui-Mamani, Carolina B., Taylor, Anne, Taylor, Julie, Tebar, William R., Tell, Grethe S., Tello, Tania, Tham, Yih Chung, Thankappan, K. R., Theobald, Holger, Theodoridis, Xenophon, Thinggaard, Mikael, Thomas, Nihal, Thorand, Barbara, Thuesen, Betina H., Timmermans, Erik J., Tjandrarini, Dwi H., Tjonneland, Anne, Toft, Ulla, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topor-Madry, Roman, Jose Tormo, Maria, Tornaritis, Michael J., Torrent, Maties, Torres-Collado, Laura, Touloumi, Giota, Traissac, Pierre, Triantafyllou, Areti, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Trinh, Oanh T. H., Trivedi, Atul, Tshepo, Lechaba, Tsugane, Shoichiro, Tuliakova, Azaliia M., Tulloch-Reid, Marshall K., Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L., Twig, Gilad, Tynelius, Per, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ulmer, Hanno, Uusitalo, Hannu M. T., Valdivia, Gonzalo, Valvi, Damaskini, van Dam, Rob M., van den Born, Bert-Jan, Van der Heyden, Johan, van der Schouw, Yvonne T., Van Herck, Koen, Hoang Van Minh, Van Schoor, Natasja M., van Valkengoed, Irene G. M., van Zutphen, Elisabeth M., Vanuzzo, Diego, Varbo, Anette, Vasan, Senthil K., Vega, Tomas, Veidebaum, Toomas, Velasquez-Melendez, Gustavo, Veronesi, Giovanni, Verschuren, W. M. Monique, Verstraeten, Roosmarijn, Victora, Cesar G., Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesus, Virtanen, Jyrki K., Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vlasoff, Tiina, Vollenweider, Peter, Voutilainen, Ari, Wade, Alisha N., Walton, Janette, Wambiya, Elvis O. A., Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, Wanderley Junior, Rildo de Souza, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S. Goya, Wareham, Nicholas, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H., Widhalm, Kurt, Wiecek, Andrzej, Wilks, Rainford J., Willeit, Johann, Willeit, Peter, Williams, Emmanuel A., Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A., Wong, Andrew, Wong, Tien Yin, Woo, Jean, Wu, Frederick C., Wu, Shouling, Wyszynska, Justyna, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K., Yoosefi, Moein, Yoshihara, Akihiro, You, San-Lin, Younger-Coleman, Novie O., Yusoff, Ahmad Faudzi, Zainuddin, Ahmad A., Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antonis, Elisa Zapata, Maria, Zaw, Ko Ko, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhao, Dong, Zhao, Ming-Hui, Zhen, Shiqi, Zheng, Yingfeng, Zholdin, Bekbolat, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Zoghlami, Nada, Zuniga Cisneros, Julio., School of Medicine, ACS - Diabetes & metabolism, APH - Global Health, Pulmonology, Medical Informatics, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Anesthesiology, Graduate School, and ACS - Heart failure & arrhythmias
Subjects: Male, Latin Americans, Nutrition and Disease, Epidemiology, [SDV]Life Sciences [q-bio], Medizin, BLOOD-PRESSURE, 030204 cardiovascular system & hematology, Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants, Hypertension, Prevalence, Control, Tretament, GUIDELINES, Global Health, Worldwide trends, 0302 clinical medicine, Hypertension prevalence, Voeding en Ziekte, Medicine and Health Sciences, kohonnut verenpaine, Medicine, 030212 general & internal medicine, Prevention and Control, 11 Medical and Health Sciences, ComputingMilieux_MISCELLANEOUS, education.field_of_study, food and beverages, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Noncommunicable diseases, Period prevalence, Middle Aged, kansainvälinen vertailu, 3142 Public health care science, environmental and occupational health, 3. Good health, MIDDLE-INCOME, Pooled analysis, SYSTEMATIC ANALYSIS, INCOME COUNTRIES, ADULTS, PREVENTION, MANAGEMENT, ADHERENCE, DIAGNOSIS, Western europe, [SDE]Environmental Sciences, Hypertension/diagnosis, NCD Risk Factor Collaboration (NCD-RisC), Female, B990 Subjects Allied to Medicine not elsewhere classified, Life Sciences & Biomedicine, Adult, health-care, esiintyvyys, Central asia, Population, Nursing, 3121 Internal medicine, 03 medical and health sciences, Medicine, General & Internal, Drug Therapy, General & Internal Medicine, Life Science, Humans, ddc:610, education, Antihypertensive Agents, VLAG, Aged, Science & Technology, Antihypertensive Agents/therapeutic use, business.industry, Omvårdnad, fungi, General and internal medicine, Estados de Saúde e de Doença, Taking medication, Treatment, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Blood pressure, Faculdade de Ciências Sociais, 3121 General medicine, internal medicine and other clinical medicine, lääkehoito, 1182 Biochemistry, cell and molecular biology, business, Demography
Abstract: Background: hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods: we used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings: the number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings., British Heart Foundation Centre of Research Excellence Grant; World Health Organization (WHO); Abdul Latif Jameel Institute for Disease and Emergency Analytics Fellowship
Published: 2021

23. Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Author: Lin WY, Fordham SE, Hungate E, Sunter NJ, Elstob C, Xu Y, Park C, Quante A, Strauch K, Gieger C, Skol A, Rahman T, Sucheston-Campbell L, Wang J, Hahn T, Clay-Gilmour AI, Jones GL, Marr HJ, Jackson GH, Menne T, Collin M, Ivey A, Hills RK, Burnett AK, Russell NH, Fitzgibbon J, Larson RA, Le Beau MM, Stock W, Heidenreich O, Alharbi A, Allsup DJ, Houlston RS, Norden J, Dickinson AM, Douglas E, Lendrem C, Daly AK, Palm L, Piechocki K, Jeffries S, Bornhäuser M, Röllig C, Altmann H, Ruhnke L, Kunadt D, Wagenführ L, Cordell HJ, Darlay R, Andersen MK, Fontana MC, Martinelli G, Marconi G, Sanz MA, Cervera J, Gómez-Seguí I, Cluzeau T, Moreilhon C, Raynaud S, Sill H, Voso MT, Lo-Coco F, Dombret H, Cheok M, Preudhomme C, Gale RE, Linch D, Gaal-Wesinger J, Masszi A, Nowak D, Hofmann WK, Gilkes A, Porkka K, Milosevic Feenstra JD, Kralovics R, Grimwade D, Meggendorfer M, Haferlach T, Krizsán S, Bödör C, Stölzel F, Onel K, and Allan JM
Subjects: RISK, HLA, OLDER PATIENTS, AML, hemic and lymphatic diseases, HUMAN-LEUKOCYTE ANTIGEN, HIF-1-ALPHA, IMMUNE ESCAPE, CLONAL EVOLUTION, CANCER, GENE-MUTATIONS
Abstract: Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10 -8 ; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10 -10 ; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA).
Published: 2021

24. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author: Gorski, M. (Mathias), Jung, B. (Bettina), Li, Y. (Yong), Matias-Garcia, P.R. (Pamela R.), Wuttke, M. (Matthias), Coassin, S. (Stefan), Thio, C.H.L. (Chris H.L.), Kleber, M.E. (Marcus E.), Winkler, T.W. (Thomas W.), Wanner, V. (Veronika), Chai, J.-F. (Jin-Fang), Chu, A.Y. (Audrey Y), Cocca, M. (Massimiliano), Feitosa, M.F. (Mary Furlan), Ghasemi, S. (Sahar), Hoppmann, A. (Anselm), Horn, K. (Katrin), Li, M. (Man), Nutile, T. (Teresa), Scholz, M. (Markus), Sieber, K.B. (Karsten B.), Teumer, A. (Alexander), Tin, A. (Adrienne), Wang, J. (Judy), Tayo, B. (Bamidele), Ahluwalia, T.S. (Tarunveer Singh), Almgren, P. (Peter), Bakker, S.J.L. (Stephan), Banas, B. (Bernhard), Bansal, N. (Nisha), Biggs, M.L. (M.), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin), Brenner, H. (Hermann), Carroll, R.J. (Robert J.), Chalmers, J. (John), Chee, M.-L. (Miao-Li), Chee, M.-L. (Miao-Ling), Cheng, C.-Y. (Ching-Yu), Coresh, J. (Josef), de Borst, M.H. (Martin H.), Degenhardt, F. (Frauke), Eckardt, K.-U. (Kai-Uwe), Endlich, K. (Karlhans), Franke, A. (Andre), Freitag-Wolf, S. (Sandra), Gampawar, P. (Piyush), Gansevoort, R.T. (Ron), Ghanbari, M. (Mohsen), Gieger, C. (Christian), Hamet, P. (Pavel), Ho, K. (Kevin), Hofer, E. (Edith), Holleczek, B. (B.), Xian Foo, V.H. (Valencia Hui), Hutri-Kähönen, N. (Nina), Hwang, S.-J. (Shih-Jen), Ikram, M.A. (Arfan), Josyula, N.S. (Navya Shilpa), Kähönen, M. (Mika), Khor, C.C., Koenig, W. (Wolfgang), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kuhnel, B. (Brigitte), Lange, L.A. (Leslie A.), Lehtimäki, T. (Terho), Lieb, W. (Wolfgang), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (H. Marike), Franke, L. (Lude), van der Harst, P. (Pim), Matullo, G., Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Abecasis, G.R. (Gonçalo), Baras, A. (Aris), Cantor, M. (Michael), Coppola, G. (Giovanni), Economides, A. (Aris), Lotta, L.A. (Luca A.), Overton, J.D. (John D.), Reid, J.G. (Jeffrey G.), Shuldiner, A. (Alan), Beechert, C. (Christina), Forsythe, C. (Caitlin), Fuller, E.D. (Erin D.), Gu, Z. (Zhenhua), Lattari, M. (Michael), Lopez, A. (Alexander), Schleicher, T.D. (Thomas D.), Padilla, M.S. (Maria Sotiropoulos), Toledo, K. (Karina), Widom, L. (Louis), Wolf, S.E. (Sarah E.), Pradhan, M. (Manasi), Manoochehri, K. (Kia), Ulloa, R.H. (Ricardo H.), Bai, X. (Xiaodong), Balasubramanian, S. (Suganthi), Barnard, L. (Leland), Blumenfeld, A. (Andrew), Eom, G. (Gisu), Habegger, L. (Lukas), Hawes, A. (Alicia), Khalid, S. (Shareef), Maxwell, E.K. (Evan K.), Salerno, W. (William), Staples, J.C. (Jeffrey C.), Jones, M.B. (Marcus B.), Mitnaul, L.J. (Lyndon), Loos, R.J.F. (Ruth J.F.), Lukas, M.A. (Mary Ann), Lyytikäinen, L.-P. (Leo-Pekka), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Milaneschi, Y. (Yuri), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Mychaleckyj, J.C. (Josyf), Nadkarni, G. (Girish), Nauck, M. (Matthias), Nikus, K. (Kjell), Ning, B. (Boting), Nolte, I.M. (Ilja), O'Donoghue, M.L. (Michelle L.), Orho-Melander, M. (Marju), Pendergrass, S.A. (Sarah), Penninx, B.W.J.H. (Brenda), Preuss, M. (Michael), Psaty, B.M. (Bruce M.), Raffield, L.M. (Laura M.), Raitakari, O. (Olli), Rettig, R. (Rainer), Rheinberger, M. (Myriam), Rice, K.M. (Kenneth M.), Rosenkranz, A.R. (Alexander R.), Rossing, K., Rotter, J.I. (Jerome I.), Sabanayagam, C. (Charumathi), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Schöttker, B. (Ben), Schulz, C.A. (Christina Alexandra), Sedaghat, S. (Sanaz), Shaffer, C.M. (Christian M.), Strauch, K. (Konstantin), Szymczak, S. (Silke), Taylor, K.D. (Kent D.), Tremblay, J. (Johanne), Chaker, L. (Layal), Most, P.J. (Peter) van der, Verweij, N. (Niek), Völker, U. (Uwe), Waldenberger, M. (Melanie), Wallentin, L.C. (Lars), Waterworth, D.M. (Dawn M.), White, H.D. (Harvey), Wilson, J.G. (James G.), Wong, T.-Y. (Tien-Yin), Woodward, M. (Mark), Yang, Q. (Qiong), Yasuda, M. (Masayuki), Yerges-Armstrong, L.M. (Laura), Zhang, Y. (Yan), Wanner, C. (Christoph), Böger, C.A. (Carsten), Köttgen, A. (Anna), Kronenberg, F. (Florian), Penninx, B.W.J.H., Heid, I.M. (Iris), Gorski, M. (Mathias), Jung, B. (Bettina), Li, Y. (Yong), Matias-Garcia, P.R. (Pamela R.), Wuttke, M. (Matthias), Coassin, S. (Stefan), Thio, C.H.L. (Chris H.L.), Kleber, M.E. (Marcus E.), Winkler, T.W. (Thomas W.), Wanner, V. (Veronika), Chai, J.-F. (Jin-Fang), Chu, A.Y. (Audrey Y), Cocca, M. (Massimiliano), Feitosa, M.F. (Mary Furlan), Ghasemi, S. (Sahar), Hoppmann, A. (Anselm), Horn, K. (Katrin), Li, M. (Man), Nutile, T. (Teresa), Scholz, M. (Markus), Sieber, K.B. (Karsten B.), Teumer, A. (Alexander), Tin, A. (Adrienne), Wang, J. (Judy), Tayo, B. (Bamidele), Ahluwalia, T.S. (Tarunveer Singh), Almgren, P. (Peter), Bakker, S.J.L. (Stephan), Banas, B. (Bernhard), Bansal, N. (Nisha), Biggs, M.L. (M.), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin), Brenner, H. (Hermann), Carroll, R.J. (Robert J.), Chalmers, J. (John), Chee, M.-L. (Miao-Li), Chee, M.-L. (Miao-Ling), Cheng, C.-Y. (Ching-Yu), Coresh, J. (Josef), de Borst, M.H. (Martin H.), Degenhardt, F. (Frauke), Eckardt, K.-U. (Kai-Uwe), Endlich, K. (Karlhans), Franke, A. (Andre), Freitag-Wolf, S. (Sandra), Gampawar, P. (Piyush), Gansevoort, R.T. (Ron), Ghanbari, M. (Mohsen), Gieger, C. (Christian), Hamet, P. (Pavel), Ho, K. (Kevin), Hofer, E. (Edith), Holleczek, B. (B.), Xian Foo, V.H. (Valencia Hui), Hutri-Kähönen, N. (Nina), Hwang, S.-J. (Shih-Jen), Ikram, M.A. (Arfan), Josyula, N.S. (Navya Shilpa), Kähönen, M. (Mika), Khor, C.C., Koenig, W. (Wolfgang), Kramer, H. (Holly), Krämer, B.K. (Bernhard), Kuhnel, B. (Brigitte), Lange, L.A. (Leslie A.), Lehtimäki, T. (Terho), Lieb, W. (Wolfgang), Alizadeh, B.Z. (Behrooz), Boezen, H.M. (H. Marike), Franke, L. (Lude), van der Harst, P. (Pim), Matullo, G., Rots, M.G. (M.), Snieder, H. (Harold), Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Abecasis, G.R. (Gonçalo), Baras, A. (Aris), Cantor, M. (Michael), Coppola, G. (Giovanni), Economides, A. (Aris), Lotta, L.A. (Luca A.), Overton, J.D. (John D.), Reid, J.G. (Jeffrey G.), Shuldiner, A. (Alan), Beechert, C. (Christina), Forsythe, C. (Caitlin), Fuller, E.D. (Erin D.), Gu, Z. (Zhenhua), Lattari, M. (Michael), Lopez, A. (Alexander), Schleicher, T.D. (Thomas D.), Padilla, M.S. (Maria Sotiropoulos), Toledo, K. (Karina), Widom, L. (Louis), Wolf, S.E. (Sarah E.), Pradhan, M. (Manasi), Manoochehri, K. (Kia), Ulloa, R.H. (Ricardo H.), Bai, X. (Xiaodong), Balasubramanian, S. (Suganthi), Barnard, L. (Leland), Blumenfeld, A. (Andrew), Eom, G. (Gisu), Habegger, L. (Lukas), Hawes, A. (Alicia), Khalid, S. (Shareef), Maxwell, E.K. (Evan K.), Salerno, W. (William), Staples, J.C. (Jeffrey C.), Jones, M.B. (Marcus B.), Mitnaul, L.J. (Lyndon), Loos, R.J.F. (Ruth J.F.), Lukas, M.A. (Mary Ann), Lyytikäinen, L.-P. (Leo-Pekka), Meisinger, C. (Christa), Meitinger, T. (Thomas), Melander, O. (Olle), Milaneschi, Y. (Yuri), Mishra, P.P. (Pashupati P.), Mononen, N. (Nina), Mychaleckyj, J.C. (Josyf), Nadkarni, G. (Girish), Nauck, M. (Matthias), Nikus, K. (Kjell), Ning, B. (Boting), Nolte, I.M. (Ilja), O'Donoghue, M.L. (Michelle L.), Orho-Melander, M. (Marju), Pendergrass, S.A. (Sarah), Penninx, B.W.J.H. (Brenda), Preuss, M. (Michael), Psaty, B.M. (Bruce M.), Raffield, L.M. (Laura M.), Raitakari, O. (Olli), Rettig, R. (Rainer), Rheinberger, M. (Myriam), Rice, K.M. (Kenneth M.), Rosenkranz, A.R. (Alexander R.), Rossing, K., Rotter, J.I. (Jerome I.), Sabanayagam, C. (Charumathi), Schmidt, H. (Helena), Schmidt, R. (Reinhold), Schöttker, B. (Ben), Schulz, C.A. (Christina Alexandra), Sedaghat, S. (Sanaz), Shaffer, C.M. (Christian M.), Strauch, K. (Konstantin), Szymczak, S. (Silke), Taylor, K.D. (Kent D.), Tremblay, J. (Johanne), Chaker, L. (Layal), Most, P.J. (Peter) van der, Verweij, N. (Niek), Völker, U. (Uwe), Waldenberger, M. (Melanie), Wallentin, L.C. (Lars), Waterworth, D.M. (Dawn M.), White, H.D. (Harvey), Wilson, J.G. (James G.), Wong, T.-Y. (Tien-Yin), Woodward, M. (Mark), Yang, Q. (Qiong), Yasuda, M. (Masayuki), Yerges-Armstrong, L.M. (Laura), Zhang, Y. (Yan), Wanner, C. (Christoph), Böger, C.A. (Carsten), Köttgen, A. (Anna), Kronenberg, F. (Florian), Penninx, B.W.J.H., and Heid, I.M. (Iris)
Abstract: Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized varia
Published: 2021
Full Text: View/download PDF

25. Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability (Nature Communications, (2021), 12, 1, (24), 10.1038/s41467-020-19366-9)

Author: Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J.L. (Josine L.), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A.J. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), Geus, E.J.C. (Eco) de, Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Matullo, G., Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth J. F.), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P. (Patricia), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Barroso, I.E. (Inês), Morris, A.P. (Andrew), Prokopenko, I. (Inga), Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J.L. (Josine L.), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A.J. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), Geus, E.J.C. (Eco) de, Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Matullo, G., Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth J. F.), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P. (Patricia), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Barroso, I.E. (Inês), Morris, A.P. (Andrew), and Prokopenko, I. (Inga)
Abstract: The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped. This has now been corrected in the PDF and HTML versions of the Article.
Published: 2021
Full Text: View/download PDF

26. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author: Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J. (Josine), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah H.), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), de Geus, E.J.C.N. (Eco J. C. N.), Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard O.), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), van Duijn, C.M. (Cornelia M.), Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy L.), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Navis, G. (Gerjan), Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P.B. (Patricia B.), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Dupuis, J. (Josée), Barroso, I.E. (Inês), Morris, A.P. (Andrew P.), Prokopenko, I. (Inga), Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J. (Josine), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah H.), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), de Geus, E.J.C.N. (Eco J. C. N.), Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard O.), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), van Duijn, C.M. (Cornelia M.), Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy L.), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Navis, G. (Gerjan), Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P.B. (Patricia B.), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Dupuis, J. (Josée), Barroso, I.E. (Inês), Morris, A.P. (Andrew P.), and Prokopenko, I. (Inga)
Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
Published: 2021
Full Text: View/download PDF

27. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author: Gorski, M, Jung, B, Li, Y, Matias-Garcia, PR, Wuttke, M, Coassin, S, Thio, CHL, Kleber, ME, Winkler, TW, Wanner, V, Chai, JF, Chu, AY, Cocca, M, Feitosa, MF, Ghasemi, S, Hoppmann, A, Horn, K, Li, M, Nutile, T, Scholz, M, Sieber, KB, Teumer, A, Tin, A, Wang, J, Tayo, BO, Ahluwalia, TS, Almgren, P, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Boerwinkle, E, Bottinger, EP, Brenner, H, Carroll, RJ, Chalmers, J, Chee, ML, Cheng, CY, Coresh, J, de Borst, MH, Degenhardt, F, Eckardt, KU, Endlich, K, Franke, A, Freitag-Wolf, S, Gampawar, P, Gansevoort, RT, Ghanbari, M, Gieger, C, Hamet, P, Ho, K, Hofer, E, Holleczek, B, Xian Foo, VH, Hutri-Kähönen, N, Hwang, SJ, Ikram, MA, Josyula, NS, Kähönen, M, Khor, CC, Koenig, W, Kramer, H, Krämer, BK, Kühnel, B, Lange, LA, Lehtimäki, T, Lieb, W, Alizadeh, BZ, Boezen, HM, Franke, L, van der Harst, P, Navis, G, Rots, M, Snieder, H, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Abecasis, G, Baras, A, Cantor, M, Coppola, G, Economides, A, Lotta, LA, Overton, JD, Reid, JG, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, ED, Gu, Z, Lattari, M, Lopez, A, Schleicher, TD, Padilla, MS, Toledo, K, Widom, L, Wolf, SE, Pradhan, M, Manoochehri, K, Gorski, M, Jung, B, Li, Y, Matias-Garcia, PR, Wuttke, M, Coassin, S, Thio, CHL, Kleber, ME, Winkler, TW, Wanner, V, Chai, JF, Chu, AY, Cocca, M, Feitosa, MF, Ghasemi, S, Hoppmann, A, Horn, K, Li, M, Nutile, T, Scholz, M, Sieber, KB, Teumer, A, Tin, A, Wang, J, Tayo, BO, Ahluwalia, TS, Almgren, P, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Boerwinkle, E, Bottinger, EP, Brenner, H, Carroll, RJ, Chalmers, J, Chee, ML, Cheng, CY, Coresh, J, de Borst, MH, Degenhardt, F, Eckardt, KU, Endlich, K, Franke, A, Freitag-Wolf, S, Gampawar, P, Gansevoort, RT, Ghanbari, M, Gieger, C, Hamet, P, Ho, K, Hofer, E, Holleczek, B, Xian Foo, VH, Hutri-Kähönen, N, Hwang, SJ, Ikram, MA, Josyula, NS, Kähönen, M, Khor, CC, Koenig, W, Kramer, H, Krämer, BK, Kühnel, B, Lange, LA, Lehtimäki, T, Lieb, W, Alizadeh, BZ, Boezen, HM, Franke, L, van der Harst, P, Navis, G, Rots, M, Snieder, H, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Abecasis, G, Baras, A, Cantor, M, Coppola, G, Economides, A, Lotta, LA, Overton, JD, Reid, JG, Shuldiner, A, Beechert, C, Forsythe, C, Fuller, ED, Gu, Z, Lattari, M, Lopez, A, Schleicher, TD, Padilla, MS, Toledo, K, Widom, L, Wolf, SE, Pradhan, M, and Manoochehri, K
Abstract: Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more (“Rapid3”; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline (“CKDi25”; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Published: 2021

28. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Author: McCartney D.L., Min J.L., Richmond R.C., Lu A.T., Sobczyk M.K., Davies G., Broer L., Guo X., Jeong A., Jung J., Kasela S., Katrinli S., Kuo P.-L., Matias-Garcia P.R., Mishra P.P., Nygaard M., Palviainen T., Patki A., Raffield L.M., Ratliff S.M., Richardson T.G., Robinson O., Soerensen M., Sun D., Tsai P.-C., van der Zee M.D., Walker R.M., Wang X., Wang Y., Xia R., Xu Z., Yao J., Zhao W., Correa A., Boerwinkle E., Dugue P.-A., Durda P., Elliott H.R., Gieger C., de Geus E.J.C., Harris S.E., Hemani G., Imboden M., Kahonen M., Kardia S.L.R., Kresovich J.K., Li S., Lunetta K.L., Mangino M., Mason D., McIntosh A.M., Mengel-From J., Moore A.Z., Murabito J.M., Ollikainen M., Pankow J.S., Pedersen N.L., Peters A., Polidoro S., Porteous D.J., Raitakari O., Rich S.S., Sandler D.P., Sillanpaa E., Smith A.K., Southey M.C., Strauch K., Tiwari H., Tanaka T., Tillin T., Uitterlinden A.G., Van Den Berg D.J., van Dongen J., Wilson J.G., Wright J., Yet I., Arnett D., Bandinelli S., Bell J.T., Binder A.M., Boomsma D.I., Chen W., Christensen K., Conneely K.N., Elliott P., Ferrucci L., Fornage M., Hagg S., Hayward C., Irvin M., Kaprio J., Lawlor D.A., Lehtimaki T., Lohoff F.W., Milani L., Milne R.L., Probst-Hensch N., Reiner A.P., Ritz B., Rotter J.I., Smith J.A., Taylor J.A., van Meurs J.B.J., Vineis P., Waldenberger M., Deary I.J., Relton C.L., Horvath S., Marioni R.E., McCartney D.L., Min J.L., Richmond R.C., Lu A.T., Sobczyk M.K., Davies G., Broer L., Guo X., Jeong A., Jung J., Kasela S., Katrinli S., Kuo P.-L., Matias-Garcia P.R., Mishra P.P., Nygaard M., Palviainen T., Patki A., Raffield L.M., Ratliff S.M., Richardson T.G., Robinson O., Soerensen M., Sun D., Tsai P.-C., van der Zee M.D., Walker R.M., Wang X., Wang Y., Xia R., Xu Z., Yao J., Zhao W., Correa A., Boerwinkle E., Dugue P.-A., Durda P., Elliott H.R., Gieger C., de Geus E.J.C., Harris S.E., Hemani G., Imboden M., Kahonen M., Kardia S.L.R., Kresovich J.K., Li S., Lunetta K.L., Mangino M., Mason D., McIntosh A.M., Mengel-From J., Moore A.Z., Murabito J.M., Ollikainen M., Pankow J.S., Pedersen N.L., Peters A., Polidoro S., Porteous D.J., Raitakari O., Rich S.S., Sandler D.P., Sillanpaa E., Smith A.K., Southey M.C., Strauch K., Tiwari H., Tanaka T., Tillin T., Uitterlinden A.G., Van Den Berg D.J., van Dongen J., Wilson J.G., Wright J., Yet I., Arnett D., Bandinelli S., Bell J.T., Binder A.M., Boomsma D.I., Chen W., Christensen K., Conneely K.N., Elliott P., Ferrucci L., Fornage M., Hagg S., Hayward C., Irvin M., Kaprio J., Lawlor D.A., Lehtimaki T., Lohoff F.W., Milani L., Milne R.L., Probst-Hensch N., Reiner A.P., Ritz B., Rotter J.I., Smith J.A., Taylor J.A., van Meurs J.B.J., Vineis P., Waldenberger M., Deary I.J., Relton C.L., Horvath S., and Marioni R.E.
Abstract: Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Result(s): Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion(s): This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Copyright © 2021, The Author(s).
Published: 2021

29. Genetic insights into biological mechanisms governing human ovarian ageing.

Author: Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., Perry J.R.B., Ruth K.S., Day F.R., Hussain J., Martinez-Marchal A., Aiken C.E., Azad A., Thompson D.J., Knoblochova L., Abe H., Tarry-Adkins J.L., Gonzalez J.M., Fontanillas P., Claringbould A., Bakker O.B., Sulem P., Walters R.G., Terao C., Turon S., Horikoshi M., Lin K., Onland-Moret N.C., Sankar A., Hertz E.P.T., Timshel P.N., Shukla V., Borup R., Olsen K.W., Aguilera P., Ferrer-Roda M., Huang Y., Stankovic S., Timmers P.R.H.J., Ahearn T.U., Alizadeh B.Z., Naderi E., Andrulis I.L., Arnold A.M., Aronson K.J., Augustinsson A., Bandinelli S., Barbieri C.M., Beaumont R.N., Becher H., Beckmann M.W., Benonisdottir S., Bergmann S., Bochud M., Boerwinkle E., Bojesen S.E., Bolla M.K., Boomsma D.I., Bowker N., Brody J.A., Broer L., Buring J.E., Campbell A., Campbell H., Castelao J.E., Catamo E., Chanock S.J., Chenevix-Trench G., Ciullo M., Corre T., Couch F.J., Cox A., Crisponi L., Cross S.S., Cucca F., Czene K., Smith G.D., de Geus E.J.C.N., de Mutsert R., De Vivo I., Demerath E.W., Dennis J., Dunning A.M., Dwek M., Eriksson M., Esko T., Fasching P.A., Faul J.D., Ferrucci L., Franceschini N., Frayling T.M., Gago-Dominguez M., Mezzavilla M., Garcia-Closas M., Gieger C., Giles G.G., Grallert H., Gudbjartsson D.F., Gudnason V., Guenel P., Haiman C.A., Hakansson N., Hall P., Hayward C., He C., He W., Heiss G., Hoffding M.K., Hopper J.L., Hottenga J.J., Hu F., Hunter D., Ikram M.A., Jackson R.D., Joaquim M.D.R., John E.M., Joshi P.K., Karasik D., Kardia S.L.R., Kartsonaki C., Karlsson R., Kitahara C.M., Kolcic I., Kooperberg C., Kraft P., Kurian A.W., Kutalik Z., La Bianca M., LaChance G., Langenberg C., Launer L.J., Laven J.S.E., Lawlor D.A., Le Marchand L., Li J., Lindblom A., Lindstrom S., Lindstrom T., Linet M., Liu Y.M., Liu S., Luan J., Magi R., Magnusson P.K.E., Mangino M., Mannermaa A., Marco B., Marten J., Martin N.G., Mbarek H., McKnight B., Medland S.E., Meisinger C., Meitinger T., Menni C., Metspalu A., Milani L., Milne R.L., Montgomery G.W., Mook-Kanamori D.O., Mulas A., Mulligan A.M., Nalls M.A., Newman A., Noordam R., Nutile T., Nyholt D.R., Olshan A.F., Olsson H., Painter J.N., Patel A.V., Pedersen N.L., Perjakova N., Peters A., Peters U., Pharoah P.D.P., Polasek O., Porcu E., Psaty B.M., Rahman I., Rennert G., Rennert H.S., Ridker P.M., Ring S.M., Robino A., Rose L.M., Rosendaal F.R., Rossouw J., Rudan I., Rueedi R., Ruggiero D., Sala C.F., Saloustros E., Sandler D.P., Sanna S., Sawyer E.J., Sarnowski C., Schlessinger D., Schmidt M.K., Schoemaker M.J., Schraut K.E., Scott C., Shekari S., Shrikhande A., Smith A.V., Smith B.H., Smith J.A., Sorice R., Southey M.C., Spector T.D., Spinelli J.J., Stampfer M., Stockl D., van Meurs J.B.J., Strauch K., Styrkarsdottir U., Swerdlow A.J., Tanaka T., Teras L.R., Teumer A., Thorsteinsdottir U., Timpson N.J., Toniolo D., Traglia M., Troester M.A., Truong T., Tyrrell J., Uitterlinden A.G., Ulivi S., Vachon C.M., Vitart V., Volker U., Vollenweider P., Volzke H., Wang Q., Wareham N.J., Weinberg C.R., Weir D.R., Wilcox A.N., van Dijk K.W., Willemsen G., Wilson J.F., Wolffenbuttel B.H.R., Wolk A., Wood A.R., Zhao W., Zygmunt M., Chen Z., Li L., Franke L., Burgess S., Deelen P., Pers T.H., Grondahl M.L., Andersen C.Y., Pujol A., Lopez-Contreras A.J., Daniel J.A., Stefansson K., Chang-Claude J., van der Schouw Y.T., Lunetta K.L., Chasman D.I., Easton D.F., Visser J.A., Ozanne S.E., Namekawa S.H., Solc P., Murabito J.M., Ong K.K., Hoffmann E.R., Murray A., Roig I., and Perry J.R.B.
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
Published: 2021

30. Genetic insights into biological mechanisms governing human ovarian ageing

Author: Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, Perry, JRB, Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, and Perry, JRB
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
Published: 2021

31. Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Author: McCartney, DL, Min, JL, Richmond, RC, Lu, AT, Sobczyk, MK, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, PR, Mishra, PP, Nygaard, M, Palviainen, T, Patki, A, Raffield, LM, Ratliff, SM, Richardson, TG, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, MD, Walker, RM, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugue, P-A, Durda, P, Elliott, HR, Gieger, C, de Geus, EJC, Harris, SE, Hemani, G, Imboden, M, Kahonen, M, Kardia, SLR, Kresovich, JK, Li, S, Lunetta, KL, Mangino, M, Mason, D, McIntosh, AM, Mengel-From, J, Moore, AZ, Murabito, JM, Ollikainen, M, Pankow, JS, Pedersen, NL, Peters, A, Polidoro, S, Porteous, DJ, Raitakari, O, Rich, SS, Sandler, DP, Sillanpaa, E, Smith, AK, Southey, MC, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, AG, van den Berg, DJ, van Dongen, J, Wilson, JG, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, JT, Binder, AM, Boomsma, DI, Chen, W, Christensen, K, Conneely, KN, Elliott, P, Ferrucci, L, Fornage, M, Hagg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, DA, Lehtimaki, T, Lohoff, FW, Milani, L, Milne, RL, Probst-Hensch, N, Reiner, AP, Ritz, B, Rotter, J, Smith, JA, Taylor, JA, van Meurs, JBJ, Vineis, P, Waldenberger, M, Deary, IJ, Relton, CL, Horvath, S, Marioni, RE, McCartney, DL, Min, JL, Richmond, RC, Lu, AT, Sobczyk, MK, Davies, G, Broer, L, Guo, X, Jeong, A, Jung, J, Kasela, S, Katrinli, S, Kuo, P-L, Matias-Garcia, PR, Mishra, PP, Nygaard, M, Palviainen, T, Patki, A, Raffield, LM, Ratliff, SM, Richardson, TG, Robinson, O, Soerensen, M, Sun, D, Tsai, P-C, van der Zee, MD, Walker, RM, Wang, X, Wang, Y, Xia, R, Xu, Z, Yao, J, Zhao, W, Correa, A, Boerwinkle, E, Dugue, P-A, Durda, P, Elliott, HR, Gieger, C, de Geus, EJC, Harris, SE, Hemani, G, Imboden, M, Kahonen, M, Kardia, SLR, Kresovich, JK, Li, S, Lunetta, KL, Mangino, M, Mason, D, McIntosh, AM, Mengel-From, J, Moore, AZ, Murabito, JM, Ollikainen, M, Pankow, JS, Pedersen, NL, Peters, A, Polidoro, S, Porteous, DJ, Raitakari, O, Rich, SS, Sandler, DP, Sillanpaa, E, Smith, AK, Southey, MC, Strauch, K, Tiwari, H, Tanaka, T, Tillin, T, Uitterlinden, AG, van den Berg, DJ, van Dongen, J, Wilson, JG, Wright, J, Yet, I, Arnett, D, Bandinelli, S, Bell, JT, Binder, AM, Boomsma, DI, Chen, W, Christensen, K, Conneely, KN, Elliott, P, Ferrucci, L, Fornage, M, Hagg, S, Hayward, C, Irvin, M, Kaprio, J, Lawlor, DA, Lehtimaki, T, Lohoff, FW, Milani, L, Milne, RL, Probst-Hensch, N, Reiner, AP, Ritz, B, Rotter, J, Smith, JA, Taylor, JA, van Meurs, JBJ, Vineis, P, Waldenberger, M, Deary, IJ, Relton, CL, Horvath, S, and Marioni, RE
Abstract: BACKGROUND: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. RESULTS: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. CONCLUSION: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
Published: 2021

32. Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function

Author: Yang, T, Jackson, VE, Smith, A, Chen, H, Bartz, TM, Sitlani, CM, Psaty, BM, Gharib, SA, O'Connor, GT, Dupuis, J, Xu, J, Lohman, K, Liu, Y, Kritchevsky, SB, Cassano, PA, Flexeder, C, Gieger, C, Karrasch, S, Peters, A, Schulz, H, Harris, SE, Starr, JM, Deary, IJ, Manichaikul, A, Oelsner, EC, Barr, RG, Taylor, KD, Rich, SS, Bonten, TN, Mook-Kanamori, DO, Noordam, R, Li-Gao, R, Jarvelin, M-R, Wielscher, M, Terzikhan, N, Lahousse, L, Brusselle, G, Weiss, S, Ewert, R, Glaeser, S, Homuth, G, Shrine, N, Hall, IP, Tobin, M, London, SJ, Wei, P, Morrison, AC, Yang, T, Jackson, VE, Smith, A, Chen, H, Bartz, TM, Sitlani, CM, Psaty, BM, Gharib, SA, O'Connor, GT, Dupuis, J, Xu, J, Lohman, K, Liu, Y, Kritchevsky, SB, Cassano, PA, Flexeder, C, Gieger, C, Karrasch, S, Peters, A, Schulz, H, Harris, SE, Starr, JM, Deary, IJ, Manichaikul, A, Oelsner, EC, Barr, RG, Taylor, KD, Rich, SS, Bonten, TN, Mook-Kanamori, DO, Noordam, R, Li-Gao, R, Jarvelin, M-R, Wielscher, M, Terzikhan, N, Lahousse, L, Brusselle, G, Weiss, S, Ewert, R, Glaeser, S, Homuth, G, Shrine, N, Hall, IP, Tobin, M, London, SJ, Wei, P, and Morrison, AC
Abstract: Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV1. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.
Published: 2021

33. Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Author: Grosche, S, Marenholz, I, Esparza-Gordillo, J, Arnau-Soler, A, Pairo-Castineira, E, Rueschendorf, F, Ahluwalia, TS, Almqvist, C, Arnold, A, Baurecht, H, Bisgaard, H, Bonnelykke, K, Brown, SJ, Bustamante, M, Curtin, JA, Custovic, A, Dharmage, SC, Esplugues, A, Falchi, M, Fernandez-Orth, D, Ferreira, MAR, Franke, A, Gerdes, S, Gieger, C, Hakonarson, H, Holt, PG, Homuth, G, Hubner, N, Hysi, PG, Jarvelin, M-R, Karlsson, R, Koppelman, GH, Lau, S, Lutz, M, Magnusson, PKE, Marks, GB, Mueller-Nurasyid, M, Noethen, MM, Paternoster, L, Pennell, CE, Peters, A, Rawlik, K, Robertson, CF, Rodriguez, E, Sebert, S, Simpson, A, Sleiman, PMA, Standl, M, Stoelzl, D, Strauch, K, Szwajda, A, Tenesa, A, Thompson, PJ, Ullemar, V, Visconti, A, Vonk, JM, Wang, CA, Weidinger, S, Wielscher, M, Worth, CL, Xu, C-J, Lee, Y-A, Grosche, S, Marenholz, I, Esparza-Gordillo, J, Arnau-Soler, A, Pairo-Castineira, E, Rueschendorf, F, Ahluwalia, TS, Almqvist, C, Arnold, A, Baurecht, H, Bisgaard, H, Bonnelykke, K, Brown, SJ, Bustamante, M, Curtin, JA, Custovic, A, Dharmage, SC, Esplugues, A, Falchi, M, Fernandez-Orth, D, Ferreira, MAR, Franke, A, Gerdes, S, Gieger, C, Hakonarson, H, Holt, PG, Homuth, G, Hubner, N, Hysi, PG, Jarvelin, M-R, Karlsson, R, Koppelman, GH, Lau, S, Lutz, M, Magnusson, PKE, Marks, GB, Mueller-Nurasyid, M, Noethen, MM, Paternoster, L, Pennell, CE, Peters, A, Rawlik, K, Robertson, CF, Rodriguez, E, Sebert, S, Simpson, A, Sleiman, PMA, Standl, M, Stoelzl, D, Strauch, K, Szwajda, A, Tenesa, A, Thompson, PJ, Ullemar, V, Visconti, A, Vonk, JM, Wang, CA, Weidinger, S, Wielscher, M, Worth, CL, Xu, C-J, and Lee, Y-A
Abstract: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
Published: 2021

34. Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data

Author: Dugue, P-A, Wilson, R, Lehne, B, Jayasekara, H, Wang, X, Jung, C-H, Joo, JE, Makalic, E, Schmidt, DF, Baglietto, L, Severi, G, Gieger, C, Ladwig, K-H, Peters, A, Kooner, JS, Southey, MC, English, DR, Waldenberger, M, Chambers, JC, Giles, GG, Milne, RL, Dugue, P-A, Wilson, R, Lehne, B, Jayasekara, H, Wang, X, Jung, C-H, Joo, JE, Makalic, E, Schmidt, DF, Baglietto, L, Severi, G, Gieger, C, Ladwig, K-H, Peters, A, Kooner, JS, Southey, MC, English, DR, Waldenberger, M, Chambers, JC, Giles, GG, and Milne, RL
Abstract: DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10-7 , 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P < .05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P < .05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood.
Published: 2021

35. Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study

Author: Matias-Garcia, PR, Wilson, R, Guo, Q, Zaghlool, SB, Eales, JM, Xu, X, Charchar, FJ, Dormer, J, Maalmi, H, Schlosser, P, Elhadad, MA, Nano, J, Sharma, S, Peters, A, Fornoni, A, Mook-Kanamori, DO, Winkelmann, J, Danesh, J, Di Angelantonio, E, Ouwehand, WH, Watkins, NA, Roberts, DJ, Petrera, A, Graumann, J, Koenig, W, Hveem, K, Jonasson, C, Koettgen, A, Butterworth, A, Prunotto, M, Hauck, S, Herder, C, Suhre, K, Gieger, C, Tomaszewski, M, Teumer, A, Waldenberger, M, Matias-Garcia, PR, Wilson, R, Guo, Q, Zaghlool, SB, Eales, JM, Xu, X, Charchar, FJ, Dormer, J, Maalmi, H, Schlosser, P, Elhadad, MA, Nano, J, Sharma, S, Peters, A, Fornoni, A, Mook-Kanamori, DO, Winkelmann, J, Danesh, J, Di Angelantonio, E, Ouwehand, WH, Watkins, NA, Roberts, DJ, Petrera, A, Graumann, J, Koenig, W, Hveem, K, Jonasson, C, Koettgen, A, Butterworth, A, Prunotto, M, Hauck, S, Herder, C, Suhre, K, Gieger, C, Tomaszewski, M, Teumer, A, and Waldenberger, M
Abstract: BACKGROUND: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. METHODS: A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. RESULTS: In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. CONCLUSIONS: In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.
Published: 2021

36. The power of genetic diversity in genome-wide association studies of lipids

Author: Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), Willer, C. J. (Cristen J.), Graham, S. E. (Sarah E.), Clarke, S. L. (Shoa L.), Wu, K. H. (Kuan-Han H.), Kanoni, S. (Stavroula), Zajac, G. J. (Greg J. M.), Ramdas, S. (Shweta), Surakka, I. (Ida), Ntalla, I. (Ioanna), Vedantam, S. (Sailaja), Winkler, T. W. (Thomas W.), Locke, A. E. (Adam E.), Marouli, E. (Eirini), Hwang, M. Y. (Mi Yeong), Han, S. (Sohee), Narita, A. (Akira), Choudhury, A. (Ananyo), Bentley, A. R. (Amy R.), Ekoru, K. (Kenneth), Verma, A. (Anurag), Trivedi, B. (Bhavi), Martin, H. C. (Hilary C.), Hunt, K. A. (Karen A.), Hui, Q. (Qin), Klarin, D. (Derek), Zhu, X. (Xiang), Thorleifsson, G. (Gudmar), Helgadottir, A. (Anna), Gudbjartsson, D. F. (Daniel F.), Holm, H. (Hilma), Olafsson, I. (Isleifur), Akiyama, M. (Masato), Sakaue, S. (Saori), Terao, C. (Chikashi), Kanai, M. (Masahiro), Zhou, W. (Wei), Brumpton, B. M. (Ben M.), Rasheed, H. (Humaira), Ruotsalainen, S. E. (Sanni E.), Havulinna, A. S. (Aki S.), Veturi, Y. (Yogasudha), Feng, Q. (QiPing), Rosenthal, E. A. (Elisabeth A.), Lingren, T. (Todd), Pacheco, J. A. (Jennifer Allen), Pendergrass, S. A. (Sarah A.), Haessler, J. (Jeffrey), Giulianini, F. (Franco), Bradford, Y. (Yuki), Miller, J. E. (Jason E.), Campbell, A. (Archie), Lin, K. (Kuang), Millwood, I. Y. (Iona Y.), Hindy, G. (George), Rasheed, A. (Asif), Faul, J. D. (Jessica D.), Zhao, W. (Wei), Weir, D. R. (David R.), Turman, C. (Constance), Huang, H. (Hongyan), Graff, M. (Mariaelisa), Mahajan, A. (Anubha), Brown, M. R. (Michael R.), Zhang, W. (Weihua), Yu, K. (Ketian), Schmidt, E. M. (Ellen M.), Pandit, A. (Anita), Gustafsson, S. (Stefan), Yin, X. (Xianyong), Luan, J. (Jian'an), Zhao, J.-H. (Jing-Hua), Matsuda, F. (Fumihiko), Jang, H.-M. (Hye-Mi), Yoon, K. (Kyungheon), Medina-Gomez, C. (Carolina), Pitsillides, A. (Achilleas), Hottenga, J. J. (Jouke Jan), Willemsen, G. (Gonneke), Wood, A. R. (Andrew R.), Ji, Y. (Yingji), Gao, Z. (Zishan), Haworth, S. (Simon), Mitchell, R. E. (Ruth E.), Chai, J. F. (Jin Fang), Aadahl, M. (Mette), Yao, J. (Jie), Manichaikul, A. (Ani), Warren, H. R. (Helen R.), Ramirez, J. (Julia), Bork-Jensen, J. (Jette), Karhus, L. L. (Line L.), Goel, A. (Anuj), Sabater-Lleal, M. (Maria), Noordam, R. (Raymond), Sidore, C. (Carlo), Fiorillo, E. (Edoardo), McDaid, A. F. (Aaron F.), Marques-Vidal, P. (Pedro), Wielscher, M. (Matthias), Trompet, S. (Stella), Sattar, N. (Naveed), Mollehave, L. T. (Line T.), Thuesen, B. H. (Betina H.), Munz, M. (Matthias), Zeng, L. (Lingyao), Huang, J. (Jianfeng), Yang, B. (Bin), Poveda, A. (Alaitz), Kurbasic, A. (Azra), Lamina, C. (Claudia), Forer, L. (Lukas), Scholz, M. (Markus), Galesloot, T. E. (Tessel E.), Bradfield, J. P. (Jonathan P.), Daw, E. W. (E. Warwick), Zmuda, J. M. (Joseph M.), Mitchell, J. S. (Jonathan S.), Fuchsberger, C. (Christian), Christensen, H. (Henry), Brody, J. A. (Jennifer A.), Feitosa, M. F. (Mary F.), Wojczynski, M. K. (Mary K.), Preuss, M. (Michael), Mangino, M. (Massimo), Christofidou, P. (Paraskevi), Verweij, N. (Niek), Benjamins, J. W. (Jan W.), Engmann, J. (Jorgen), Kember, R. L. (Rachel L.), Slieker, R. C. (Roderick C.), Lo, K. S. (Ken Sin), Zilhao, N. R. (Nuno R.), Kleber, M. E. (Marcus E.), Delgado, G. E. (Graciela E.), Huo, S. (Shaofeng), Ikeda, D. D. (Daisuke D.), Iha, H. (Hiroyuki), Yang, J. (Jian), Liu, J. (Jun), Leonard, H. L. (Hampton L.), Marten, J. (Jonathan), Schmidt, B. (Borge), Arendt, M. (Marina), Smyth, L. J. (Laura J.), Canadas-Garre, M. (Marisa), Wang, C. (Chaolong), Nakatochi, M. (Masahiro), Wong, A. (Andrew), Hutri-Kahonen, N. (Nina), Sim, X. (Xueling), Xia, R. (Rui), Huerta-Chagoya, A. (Alicia), Fernandez-Lopez, J. C. (Juan Carlos), Lyssenko, V. (Valeriya), Ahmed, M. (Meraj), Jackson, A. U. (Anne U.), Irvin, M. R. (Marguerite R.), Oldmeadow, C. (Christopher), Kim, H.-N. (Han-Na), Ryu, S. (Seungho), Timmers, P. R. (Paul R. H. J.), Arbeeva, L. (Liubov), Dorajoo, R. (Rajkumar), Lange, L. A. (Leslie A.), Chai, X. (Xiaoran), Prasad, G. (Gauri), Lores-Motta, L. (Laura), Pauper, M. (Marc), Long, J. (Jirong), Li, X. (Xiaohui), Theusch, E. (Elizabeth), Takeuchi, F. (Fumihiko), Spracklen, C. N. (Cassandra N.), Loukola, A. (Anu), Bollepalli, S. (Sailalitha), Warner, S. C. (Sophie C.), Wang, Y. X. (Ya Xing), Wei, W. B. (Wen B.), Nutile, T. (Teresa), Ruggiero, D. (Daniela), Sung, Y. J. (Yun Ju), Hung, Y.-J. (Yi-Jen), Chen, S. (Shufeng), Liu, F. (Fangchao), Yang, J. (Jingyun), Kentistou, K. A. (Katherine A.), Gorski, M. (Mathias), Brumat, M. (Marco), Meidtner, K. (Karina), Bielak, L. F. (Lawrence F.), Smith, J. A. (Jennifer A.), Hebbar, P. (Prashantha), Farmaki, A.-E. (Aliki-Eleni), Hofer, E. (Edith), Lin, M. (Maoxuan), Xue, C. (Chao), Zhang, J. (Jifeng), Concas, M. P. (Maria Pina), Vaccargiu, S. (Simona), van der Most, P. J. (Peter J.), Pitkanen, N. (Niina), Cade, B. E. (Brian E.), Lee, J. (Jiwon), van Der Laan, S. W. (Sander W.), Chitrala, K. N. (Kumaraswamy Naidu), Weiss, S. (Stefan), Zimmermann, M. E. (Martina E.), Lee, J. Y. (Jong Young), Choi, H. S. (Hyeok Sun), Nethander, M. (Maria), Freitag-Wolf, S. (Sandra), Southam, L. (Lorraine), Rayner, N. W. (Nigel W.), Wang, C. A. (Carol A.), Lin, S.-Y. (Shih-Yi), Wang, J.-S. (Jun-Sing), Couture, C. (Christian), Lyytikainen, L.-P. (Leo-Pekka), Nikus, K. (Kjell), Cuellar-Partida, G. (Gabriel), Vestergaard, H. (Henrik), Hildalgo, B. (Bertha), Giannakopoulou, O. (Olga), Cai, Q. (Qiuyin), Obura, M. O. (Morgan O.), van Setten, J. (Jessica), Li, X. (Xiaoyin), Schwander, K. (Karen), Terzikhan, N. (Natalie), Shin, J. H. (Jae Hun), Jackson, R. D. (Rebecca D.), Reiner, A. P. (Alexander P.), Martin, L. W. (Lisa Warsinger), Chen, Z. (Zhengming), Li, L. (Liming), Highland, H. M. (Heather M.), Young, K. L. (Kristin L.), Kawaguchi, T. (Takahisa), Thiery, J. (Joachim), Bis, J. C. (Joshua C.), Nadkarni, G. N. (Girish N.), Launer, L. J. (Lenore J.), Li, H. (Huaixing), Nalls, M. A. (Mike A.), Raitakari, O. T. (Olli T.), Ichihara, S. (Sahoko), Wild, S. H. (Sarah H.), Nelson, C. P. (Christopher P.), Campbell, H. (Harry), Jager, S. (Susanne), Nabika, T. (Toru), Al-Mulla, F. (Fahd), Niinikoski, H. (Harri), Braund, P. S. (Peter S.), Kolcic, I. (Ivana), Kovacs, P. (Peter), Giardoglou, T. (Tota), Katsuya, T. (Tomohiro), Bhatti, F. (Fatima), de Kleijn, D. (Dominique), de Borst, G. J. (Gert J.), Kim, E. K. (Eung Kweon), Adams, H. H. (Hieab H. H.), Ikram, M. A. (M. Arfan), Zhu, X. (Xiaofeng), Asselbergs, F. W. (Folkert W.), Kraaijeveld, A. O. (Adriaan O.), Beulens, J. W. (Joline W. J.), Shu, X.-O. (Xiao-Ou), Rallidis, L. S. (Loukianos S.), Pedersen, O. (Oluf), Hansen, T. (Torben), Mitchell, P. (Paul), Hewitt, A. W. (Alex W.), Kahonen, M. (Mika), Perusse, L. (Louis), Bouchard, C. (Claude), Tonjes, A. (Anke), Chen, Y. I. (Yii-Der Ida), Pennell, C. E. (Craig E.), Mori, T. A. (Trevor A.), Lieb, W. (Wolfgang), Franke, A. (Andre), Ohlsson, C. (Claes), Mellstrom, D. (Dan), Cho, Y. S. (Yoon Shin), Lee, H. (Hyejin), Yuan, J.-M. (Jian-Min), Koh, W.-P. (Woon-Puay), Rhee, S. Y. (Sang Youl), Woo, J.-T. (Jeong-Taek), Heid, I. M. (Iris M.), Stark, K. J. (Klaus J.), Volzke, H. (Henry), Homuth, G. (Georg), Evans, M. K. (Michele K.), Zonderman, A. B. (Alan B.), Polasek, O. (Ozren), Pasterkamp, G. (Gerard), Hoefer, I. E. (Imo E.), Redline, S. (Susan), Pahkala, K. (Katja), Oldehinkel, A. J. (Albertine J.), Snieder, H. (Harold), Biino, G. (Ginevra), Schmidt, R. (Reinhold), Schmidt, H. (Helena), Chen, Y. E. (Y. Eugene), Bandinelli, S. (Stefania), Dedoussis, G. (George), Thanaraj, T. A. (Thangavel Alphonse), Kardia, S. L. (Sharon L. R.), Kato, N. (Norihiro), Schulze, M. B. (Matthias B.), Girotto, G. (Giorgia), Jung, B. (Bettina), Boger, C. A. (Carsten A.), Joshi, P. K. (Peter K.), Bennett, D. A. (David A.), De Jager, P. L. (Philip L.), Lu, X. (Xiangfeng), Mamakou, V. (Vasiliki), Brown, M. (Morris), Caulfield, M. J. (Mark J.), Munroe, P. B. (Patricia B.), Guo, X. (Xiuqing), Ciullo, M. (Marina), Jonas, J. B. (Jost B.), Samani, N. J. (Nilesh J.), Kaprio, J. (Jaakko), Pajukanta, P. (Paivi), Adair, L. S. (Linda S.), Bechayda, S. A. (Sonny Augustin), de Silva, H. J. (H. Janaka), Wickremasinghe, A. R. (Ananda R.), Krauss, R. M. (Ronald M.), Wu, J.-Y. (Jer-Yuarn), Zheng, W. (Wei), den Hollander, A. I. (Anneke, I), Bharadwaj, D. (Dwaipayan), Correa, A. (Adolfo), Wilson, J. G. (James G.), Lind, L. (Lars), Heng, C.-K. (Chew-Kiat), Nelson, A. E. (Amanda E.), Golightly, Y. M. (Yvonne M.), Wilson, J. F. (James F.), Penninx, B. (Brenda), Kim, H.-L. (Hyung-Lae), Attia, J. (John), Scott, R. J. (Rodney J.), Rao, D. C. (D. C.), Arnett, D. K. (Donna K.), Walker, M. (Mark), Koistinen, H. A. (Heikki A.), Chandak, G. R. (Giriraj R.), Yajnik, C. S. (Chittaranjan S.), Mercader, J. M. (Josep M.), Tusie-Luna, T. (Teresa), Aguilar-Salinas, C. A. (Carlos A.), Villalpando, C. G. (Clicerio Gonzalez), Orozco, L. (Lorena), Fornage, M. (Myriam), Tai, E. S. (E. Shyong), van Dam, R. M. (Rob M.), Lehtimaki, T. (Terho), Chaturvedi, N. (Nish), Yokota, M. (Mitsuhiro), Liu, J. (Jianjun), Reilly, D. F. (Dermot F.), McKnight, A. J. (Amy Jayne), Kee, F. (Frank), Jockel, K.-H. (Karl-Heinz), McCarthy, M. I. (Mark, I), Palmer, C. N. (Colin N. A.), Vitart, V. (Veronique), Hayward, C. (Caroline), Simonsick, E. (Eleanor), van Duijn, C. M. (Cornelia M.), Lu, F. (Fan), Qu, J. (Jia), Hishigaki, H. (Haretsugu), Lin, X. (Xu), Marz, W. (Winfried), Parra, E. J. (Esteban J.), Cruz, M. (Miguel), Gudnason, V. (Vilmundur), Tardif, J.-C. (Jean-Claude), Lettre, G. (Guillaume), Elders, P. J. (Petra J. M.), Damrauer, S. M. (Scott M.), Kumari, M. (Meena), Kivimaki, M. (Mika), van der Harst, P. (Pim), Spector, T. D. (Tim D.), Loos, R. J. (Ruth J. F.), Province, M. A. (Michael A.), Psaty, B. M. (Bruce M.), Brandslund, I. (Ivan), Pramstaller, P. P. (Peter P.), Christensen, K. (Kaare), Ripatti, S. (Samuli), Widen, E. (Elisabeth), Hakonarson, H. (Hakon), Grant, S. F. (Struan F. A.), Kiemeney, L. A. (Lambertus A. L. M.), de Graaf, J. (Jacqueline), Loeffler, M. (Markus), Kronenberg, F. (Florian), Gu, D. (Dongfeng), Erdmann, J. (Jeanette), Schunkert, H. (Heribert), Franks, P. W. (Paul W.), Linneberg, A. (Allan), Jukema, J. W. (J. Wouter), Khera, A. V. (Amit, V), Männikkö, M. (Minna), Järvelin, M.-R. (Marjo-Riitta), Kutalik, Z. (Zoltan), Cucca, F. (Francesco), Mook-Kanamori, D. O. (Dennis O.), van Dijk, K. W. (Ko Willems), Watkins, H. (Hugh), Strachan, D. P. (David P.), Grarup, N. (Niels), Sever, P. (Peter), Poulter, N. (Neil), Rotter, J. I. (Jerome, I), Dantoft, T. M. (Thomas M.), Karpe, F. (Fredrik), Neville, M. J. (Matt J.), Timpson, N. J. (Nicholas J.), Cheng, C.-Y. (Ching-Yu), Wong, T.-Y. (Tien-Yin), Khor, C. C. (Chiea Chuen), Sabanayagam, C. (Charumathi), Peters, A. (Annette), Gieger, C. (Christian), Hattersley, A. T. (Andrew T.), Pedersen, N. L. (Nancy L.), Magnusson, P. K. (Patrik K. E.), Boomsma, D. I. (Dorret, I), de Geus, E. J. (Eco J. C.), Cupples, L. A. (L. Adrienne), van Meurs, J. B. (Joyce B. J.), Ghanbari, M. (Mohsen), Rsen, P. G. (Penny Gordon-La), Huang, W. (Wei), Kim, Y. J. (Young Jin), Tabara, Y. (Yasuharu), Wareham, N. J. (Nicholas J.), Langenberg, C. (Claudia), Zeggini, E. (Eleftheria), Kuusisto, J. (Johanna), Laakso, M. (Markku), Ingelsson, E. (Erik), Abecasis, G. (Goncalo), Chambers, J. C. (John C.), Kooner, J. S. (Jaspal S.), de Vries, P. S. (Paul S.), Morrison, A. C. (Alanna C.), North, K. E. (Kari E.), Daviglus, M. (Martha), Kraft, P. (Peter), Martin, N. G. (Nicholas G.), Whitfield, J. B. (John B.), Abbas, S. (Shahid), Saleheen, D. (Danish), Walters, R. G. (Robin G.), Holmes, M. V. (Michael, V), Black, C. (Corri), Smith, B. H. (Blair H.), Justice, A. E. (Anne E.), Baras, A. (Aris), Buring, J. E. (Julie E.), Ridker, P. M. (Paul M.), Chasman, D. I. (Daniel, I), Kooperberg, C. (Charles), Wei, W.-Q. (Wei-Qi), Jarvik, G. P. (Gail P.), Namjou, B. (Bahram), Hayes, M. G. (M. Geoffrey), Ritchie, M. D. (Marylyn D.), Jousilahti, P. (Pekka), Salomaa, V. (Veikko), Hveem, K. (Kristian), Asvold, B. O. (Bjorn Olav), Kubo, M. (Michiaki), Kamatani, Y. (Yoichiro), Okada, Y. (Yukinori), Murakami, Y. (Yoshinori), Thorsteinsdottir, U. (Unnur), Stefansson, K. (Kari), Ho, Y.-L. (Yuk-Lam), Lynch, J. A. (Julie A.), Rader, D. J. (Daniel J.), Tsao, P. S. (Philip S.), Chang, K.-M. (Kyong-Mi), Cho, K. (Kelly), O'Donnell, C. J. (Christopher J.), Gaziano, J. M. (John M.), Wilson, P. (Peter), Rotimi, C. N. (Charles N.), Hazelhurst, S. (Scott), Ramsay, M. (Michele), Trembath, R. C. (Richard C.), van Heel, D. A. (David A.), Tamiya, G. (Gen), Yamamoto, M. (Masayuki), Kim, B.-J. (Bong-Jo), Mohlke, K. L. (Karen L.), Frayling, T. M. (Timothy M.), Hirschhorn, J. N. (Joel N.), Kathiresan, S. (Sekar), Boehnke, M. (Michael), Natarajan, P. (Pradeep), Peloso, G. M. (Gina M.), Brown, C. D. (Christopher D.), Morris, A. P. (Andrew P.), Assimes, T. L. (Themistocles L.), Deloukas, P. (Panos), Sun, Y. V. (Yan, V), and Willer, C. J. (Cristen J.)
Abstract: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS4‐23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns24. Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.
Published: 2021

37. Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Author: Grosche, S. (Sarah), Marenholz, I. (Ingo), Esparza-Gordillo, J. (Jorge), Arnau-Soler, A. (Aleix), Pairo-Castineira, E. (Erola), Rueschendorf, F. (Franz), Ahluwalia, T. S. (Tarunveer S.), Almqvist, C. (Catarina), Arnold, A. (Andreas), Baurecht, H. (Hansjoerg), Bisgaard, H. (Hans), Bonnelykke, K. (Klaus), Brown, S. J. (Sara J.), Bustamante, M. (Mariona), Curtin, J. A. (John A.), Custovic, A. (Adnan), Dharmage, S. C. (Shyamali C.), Esplugues, A. (Ana), Falchi, M. (Mario), Fernandez-Orth, D. (Dietmar), Ferreira, M. A. (Manuel A. R.), Franke, A. (Andre), Gerdes, S. (Sascha), Gieger, C. (Christian), Hakonarson, H. (Hakon), Holt, P. G. (Patrick G.), Homuth, G. (Georg), Hubner, N. (Norbert), Hysi, P. G. (Pirro G.), Järvelin, M.-R. (Marjo-Riitta), Karlsson, R. (Robert), Koppelman, G. H. (Gerard H.), Lau, S. (Susanne), Lutz, M. (Manuel), Magnusson, P. K. (Patrik K. E.), Marks, G. B. (Guy B.), Mueller-Nurasyid, M. (Martina), Noethen, M. M. (Markus M.), Paternoster, L. (Lavinia), Pennell, C. E. (Craig E.), Peters, A. (Annette), Rawlik, K. (Konrad), Robertson, C. F. (Colin F.), Rodriguez, E. (Elke), Sebert, S. (Sylvain), Simpson, A. (Angela), Sleiman, P. M. (Patrick M. A.), Standl, M. (Marie), Stoelzl, D. (Dora), Strauch, K. (Konstantin), Szwajda, A. (Agnieszka), Tenesa, A. (Albert), Thompson, P. J. (Philip J.), Ullemar, V. (Vilhelmina), Visconti, A. (Alessia), Vonk, J. M. (Judith M.), Wang, C. A. (Carol A.), Weidinger, S. (Stephan), Wielscher, M. (Matthias), Worth, C. L. (Catherine L.), Xu, C.-J. (Chen-Jian), Lee, Y.-A. (Young-Ae), Grosche, S. (Sarah), Marenholz, I. (Ingo), Esparza-Gordillo, J. (Jorge), Arnau-Soler, A. (Aleix), Pairo-Castineira, E. (Erola), Rueschendorf, F. (Franz), Ahluwalia, T. S. (Tarunveer S.), Almqvist, C. (Catarina), Arnold, A. (Andreas), Baurecht, H. (Hansjoerg), Bisgaard, H. (Hans), Bonnelykke, K. (Klaus), Brown, S. J. (Sara J.), Bustamante, M. (Mariona), Curtin, J. A. (John A.), Custovic, A. (Adnan), Dharmage, S. C. (Shyamali C.), Esplugues, A. (Ana), Falchi, M. (Mario), Fernandez-Orth, D. (Dietmar), Ferreira, M. A. (Manuel A. R.), Franke, A. (Andre), Gerdes, S. (Sascha), Gieger, C. (Christian), Hakonarson, H. (Hakon), Holt, P. G. (Patrick G.), Homuth, G. (Georg), Hubner, N. (Norbert), Hysi, P. G. (Pirro G.), Järvelin, M.-R. (Marjo-Riitta), Karlsson, R. (Robert), Koppelman, G. H. (Gerard H.), Lau, S. (Susanne), Lutz, M. (Manuel), Magnusson, P. K. (Patrik K. E.), Marks, G. B. (Guy B.), Mueller-Nurasyid, M. (Martina), Noethen, M. M. (Markus M.), Paternoster, L. (Lavinia), Pennell, C. E. (Craig E.), Peters, A. (Annette), Rawlik, K. (Konrad), Robertson, C. F. (Colin F.), Rodriguez, E. (Elke), Sebert, S. (Sylvain), Simpson, A. (Angela), Sleiman, P. M. (Patrick M. A.), Standl, M. (Marie), Stoelzl, D. (Dora), Strauch, K. (Konstantin), Szwajda, A. (Agnieszka), Tenesa, A. (Albert), Thompson, P. J. (Philip J.), Ullemar, V. (Vilhelmina), Visconti, A. (Alessia), Vonk, J. M. (Judith M.), Wang, C. A. (Carol A.), Weidinger, S. (Stephan), Wielscher, M. (Matthias), Worth, C. L. (Catherine L.), Xu, C.-J. (Chen-Jian), and Lee, Y.-A. (Young-Ae)
Abstract: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema.
Published: 2021

38. Meta-analyses identify DNA methylation associated with kidney function and damage

Author: Schlosser, P. (Pascal), Tin, A. (Adrienne), Matias-Garcia, P. R. (Pamela R.), Thio, C. H. (Chris H. L.), Joehanes, R. (Roby), Liu, H. (Hongbo), Weihs, A. (Antoine), Yu, Z. (Zhi), Hoppmann, A. (Anselm), Grundner-Culemann, F. (Franziska), Min, J. L. (Josine L.), Adeyemo, A. A. (Adebowale A.), Agyemang, C. (Charles), Arnlov, J. (Johan), Aziz, N. A. (Nasir A.), Baccarelli, A. (Andrea), Bochud, M. (Murielle), Brenner, H. (Hermann), Breteler, M. M. (Monique M. B.), Carmeli, C. (Cristian), Chaker, L. (Layal), Chambers, J. C. (John C.), Cole, S. A. (Shelley A.), Coresh, J. (Josef), Corre, T. (Tanguy), Correa, A. (Adolfo), Cox, S. R. (Simon R.), de Klein, N. (Niek), Delgado, G. E. (Graciela E.), Domingo-Relloso, A. (Arce), Eckardt, K.-U. (Kai-Uwe), Ekici, A. B. (Arif B.), Endlich, K. (Karlhans), Evans, K. L. (Kathryn L.), Floyd, J. S. (James S.), Fornage, M. (Myriam), Franke, L. (Lude), Fraszczyk, E. (Eliza), Gao, X. (Xu), Gao, X. (Xin), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Gieger, C. (Christian), Greenland, P. (Philip), Grove, M. L. (Megan L.), Harris, S. E. (Sarah E.), Hemani, G. (Gibran), Henneman, P. (Peter), Herder, C. (Christian), Horvath, S. (Steve), Hou, L. (Lifang), Hurme, M. A. (Mikko A.), Hwang, S.-J. (Shih-Jen), Järvelin, M.-R. (Marjo-Riitta), Kardia, S. L. (Sharon L. R.), Kasela, S. (Silva), Kleber, M. E. (Marcus E.), Koenig, W. (Wolfgang), Kooner, J. S. (Jaspal S.), Kramer, H. (Holly), Kronenberg, F. (Florian), Kuhnel, B. (Brigitte), Lehtimaki, T. (Terho), Lind, L. (Lars), Liu, D. (Dan), Liu, Y. (Yongmei), Lloyd-Jones, D. M. (Donald M.), Lohman, K. (Kurt), Lorkowski, S. (Stefan), Lu, A. T. (Ake T.), Marioni, R. E. (Riccardo E.), Marz, W. (Winfried), McCartney, D. L. (Daniel L.), Meeks, K. A. (Karlijn A. C.), Milani, L. (Lili), Mishra, P. P. (Pashupati P.), Nauck, M. (Matthias), Navas-Acien, A. (Ana), Nowak, C. (Christoph), Peters, A. (Annette), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ratliff, S. M. (Scott M.), Reiner, A. P. (Alex P.), Rosas, S. E. (Sylvia E.), Schottker, B. (Ben), Schwartz, J. (Joel), Sedaghat, S. (Sanaz), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Stocker, H. R. (Hannah R.), Stringhini, S. (Silvia), Sundstrom, J. (Johan), Swenson, B. R. (Brenton R.), Tellez-Plaza, M. (Maria), van Meurs, J. B. (Joyce B. J.), van Vliet-Ostaptchouk, J. V. (Jana V.), Venema, A. (Andrea), Verweij, N. (Niek), Walker, R. M. (Rosie M.), Wielscher, M. (Matthias), Winkelmann, J. (Juliane), Wolffenbuttel, B. H. (Bruce H. R.), Zhao, W. (Wei), Zheng, Y. (Yinan), Loh, M. (Marie), Snieder, H. (Harold), Levy, D. (Daniel), Waldenberger, M. (Melanie), Susztak, K. (Katalin), Kottgen, A. (Anna), Teumer, A. (Alexander), Schlosser, P. (Pascal), Tin, A. (Adrienne), Matias-Garcia, P. R. (Pamela R.), Thio, C. H. (Chris H. L.), Joehanes, R. (Roby), Liu, H. (Hongbo), Weihs, A. (Antoine), Yu, Z. (Zhi), Hoppmann, A. (Anselm), Grundner-Culemann, F. (Franziska), Min, J. L. (Josine L.), Adeyemo, A. A. (Adebowale A.), Agyemang, C. (Charles), Arnlov, J. (Johan), Aziz, N. A. (Nasir A.), Baccarelli, A. (Andrea), Bochud, M. (Murielle), Brenner, H. (Hermann), Breteler, M. M. (Monique M. B.), Carmeli, C. (Cristian), Chaker, L. (Layal), Chambers, J. C. (John C.), Cole, S. A. (Shelley A.), Coresh, J. (Josef), Corre, T. (Tanguy), Correa, A. (Adolfo), Cox, S. R. (Simon R.), de Klein, N. (Niek), Delgado, G. E. (Graciela E.), Domingo-Relloso, A. (Arce), Eckardt, K.-U. (Kai-Uwe), Ekici, A. B. (Arif B.), Endlich, K. (Karlhans), Evans, K. L. (Kathryn L.), Floyd, J. S. (James S.), Fornage, M. (Myriam), Franke, L. (Lude), Fraszczyk, E. (Eliza), Gao, X. (Xu), Gao, X. (Xin), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Gieger, C. (Christian), Greenland, P. (Philip), Grove, M. L. (Megan L.), Harris, S. E. (Sarah E.), Hemani, G. (Gibran), Henneman, P. (Peter), Herder, C. (Christian), Horvath, S. (Steve), Hou, L. (Lifang), Hurme, M. A. (Mikko A.), Hwang, S.-J. (Shih-Jen), Järvelin, M.-R. (Marjo-Riitta), Kardia, S. L. (Sharon L. R.), Kasela, S. (Silva), Kleber, M. E. (Marcus E.), Koenig, W. (Wolfgang), Kooner, J. S. (Jaspal S.), Kramer, H. (Holly), Kronenberg, F. (Florian), Kuhnel, B. (Brigitte), Lehtimaki, T. (Terho), Lind, L. (Lars), Liu, D. (Dan), Liu, Y. (Yongmei), Lloyd-Jones, D. M. (Donald M.), Lohman, K. (Kurt), Lorkowski, S. (Stefan), Lu, A. T. (Ake T.), Marioni, R. E. (Riccardo E.), Marz, W. (Winfried), McCartney, D. L. (Daniel L.), Meeks, K. A. (Karlijn A. C.), Milani, L. (Lili), Mishra, P. P. (Pashupati P.), Nauck, M. (Matthias), Navas-Acien, A. (Ana), Nowak, C. (Christoph), Peters, A. (Annette), Prokisch, H. (Holger), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Ratliff, S. M. (Scott M.), Reiner, A. P. (Alex P.), Rosas, S. E. (Sylvia E.), Schottker, B. (Ben), Schwartz, J. (Joel), Sedaghat, S. (Sanaz), Smith, J. A. (Jennifer A.), Sotoodehnia, N. (Nona), Stocker, H. R. (Hannah R.), Stringhini, S. (Silvia), Sundstrom, J. (Johan), Swenson, B. R. (Brenton R.), Tellez-Plaza, M. (Maria), van Meurs, J. B. (Joyce B. J.), van Vliet-Ostaptchouk, J. V. (Jana V.), Venema, A. (Andrea), Verweij, N. (Niek), Walker, R. M. (Rosie M.), Wielscher, M. (Matthias), Winkelmann, J. (Juliane), Wolffenbuttel, B. H. (Bruce H. R.), Zhao, W. (Wei), Zheng, Y. (Yinan), Loh, M. (Marie), Snieder, H. (Harold), Levy, D. (Daniel), Waldenberger, M. (Melanie), Susztak, K. (Katalin), Kottgen, A. (Anna), and Teumer, A. (Alexander)
Abstract: Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
Published: 2021

39. Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function

Author: Yang, T. (Tianzhong), Jackson, V. E. (Victoria E.), Smith, A. V. (Albert V.), Chen, H. (Han), Bartz, T. M. (Traci M.), Sitlani, C. M. (Colleen M.), Psaty, B. M. (Bruce M.), Gharib, S. A. (Sina A.), O’Connor, G. T. (George T.), Dupuis, J. (Josée), Xu, J. (Jiayi), Lohman, K. (Kurt), Liu, Y. (Yongmei), Kritchevsky, S. B. (Stephen B.), Cassano, P. A. (Patricia A.), Flexeder, C. (Claudia), Gieger, C. (Christian), Karrasch, S. (Stefan), Peters, A. (Annette), Schulz, H. (Holger), Harris, S. E. (Sarah E.), Starr, J. M. (John M.), Deary, I. J. (Ian J.), Manichaikul, A. (Ani), Oelsner, E. C. (Elizabeth C.), Barr, R. G. (R. G.), Taylor, K. D. (Kent D.), Rich, S. S. (Stephen S.), Bonten, T. N. (Tobias N.), Mook-Kanamori, D. O. (Dennis O.), Noordam, R. (Raymond), Li-Gao, R. (Ruifang), Jarvelin, M.-R. (Marjo-Riitta), Wielscher, M. (Matthias), Terzikhan, N. (Natalie), Lahousse, L. (Lies), Brusselle, G. (Guy), Weiss, S. (Stefan), Ewert, R. (Ralf), Gläser, S. (Sven), Homuth, G. (Georg), Shrine, N. (Nick), Hall, I. P. (Ian P.), Tobin, M. (Martin), London, S. J. (Stephanie J.), Wei, P. (Peng), Morrison, A. C. (Alanna C.), Yang, T. (Tianzhong), Jackson, V. E. (Victoria E.), Smith, A. V. (Albert V.), Chen, H. (Han), Bartz, T. M. (Traci M.), Sitlani, C. M. (Colleen M.), Psaty, B. M. (Bruce M.), Gharib, S. A. (Sina A.), O’Connor, G. T. (George T.), Dupuis, J. (Josée), Xu, J. (Jiayi), Lohman, K. (Kurt), Liu, Y. (Yongmei), Kritchevsky, S. B. (Stephen B.), Cassano, P. A. (Patricia A.), Flexeder, C. (Claudia), Gieger, C. (Christian), Karrasch, S. (Stefan), Peters, A. (Annette), Schulz, H. (Holger), Harris, S. E. (Sarah E.), Starr, J. M. (John M.), Deary, I. J. (Ian J.), Manichaikul, A. (Ani), Oelsner, E. C. (Elizabeth C.), Barr, R. G. (R. G.), Taylor, K. D. (Kent D.), Rich, S. S. (Stephen S.), Bonten, T. N. (Tobias N.), Mook-Kanamori, D. O. (Dennis O.), Noordam, R. (Raymond), Li-Gao, R. (Ruifang), Jarvelin, M.-R. (Marjo-Riitta), Wielscher, M. (Matthias), Terzikhan, N. (Natalie), Lahousse, L. (Lies), Brusselle, G. (Guy), Weiss, S. (Stefan), Ewert, R. (Ralf), Gläser, S. (Sven), Homuth, G. (Georg), Shrine, N. (Nick), Hall, I. P. (Ian P.), Tobin, M. (Martin), London, S. J. (Stephanie J.), Wei, P. (Peng), and Morrison, A. C. (Alanna C.)
Abstract: Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV₁), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV₁. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function.
Published: 2021

40. Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

Author: Crawford, A. A. (Andrew A.), Bankier, S. (Sean), Altmaier, E. (Elisabeth), Barnes, C. L. (Catriona L. K.), Clark, D. W. (David W.), Ermel, R. (Raili), Friedrich, N. (Nele), van der Harst, P. (Pim), Joshi, P. K. (Peter K.), Karhunen, V. (Ville), Lahti, J. (Jari), Mahajan, A. (Anubha), Mangino, M. (Massimo), Nethander, M. (Maria), Neumann, A. (Alexander), Pietzner, M. (Maik), Sukhavasi, K. (Katyayani), Wang, C. A. (Carol A.), Bakker, S. J. (Stephan J. L.), Bjorkegren, J. L. (Johan L. M.), Campbell, H. (Harry), Eriksson, J. (Johan), Gieger, C. (Christian), Hayward, C. (Caroline), Järvelin, M.-R. (Marjo-Riitta), McLachlan, S. (Stela), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Pennell, C. E. (Craig E.), Price, J. (Jackie), Rudan, I. (Igor), Ruusalepp, A. (Arno), Spector, T. (Tim), Tiemeier, H. (Henning), Volzke, H. (Henry), Wilson, J. F. (James F.), Michoel, T. (Tom), Timpson, N. J. (Nicolas J.), Smith, G. D. (George Davey), Walker, B. R. (Brian R.), Crawford, A. A. (Andrew A.), Bankier, S. (Sean), Altmaier, E. (Elisabeth), Barnes, C. L. (Catriona L. K.), Clark, D. W. (David W.), Ermel, R. (Raili), Friedrich, N. (Nele), van der Harst, P. (Pim), Joshi, P. K. (Peter K.), Karhunen, V. (Ville), Lahti, J. (Jari), Mahajan, A. (Anubha), Mangino, M. (Massimo), Nethander, M. (Maria), Neumann, A. (Alexander), Pietzner, M. (Maik), Sukhavasi, K. (Katyayani), Wang, C. A. (Carol A.), Bakker, S. J. (Stephan J. L.), Bjorkegren, J. L. (Johan L. M.), Campbell, H. (Harry), Eriksson, J. (Johan), Gieger, C. (Christian), Hayward, C. (Caroline), Järvelin, M.-R. (Marjo-Riitta), McLachlan, S. (Stela), Morris, A. P. (Andrew P.), Ohlsson, C. (Claes), Pennell, C. E. (Craig E.), Price, J. (Jackie), Rudan, I. (Igor), Ruusalepp, A. (Arno), Spector, T. (Tim), Tiemeier, H. (Henning), Volzke, H. (Henry), Wilson, J. F. (James F.), Michoel, T. (Tom), Timpson, N. J. (Nicolas J.), Smith, G. D. (George Davey), and Walker, B. R. (Brian R.)
Abstract: The stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from similar to 2.2 M to similar to 7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and alpha 1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06–0.59) and myocardial infarction (0.21, 95% CI 0.00–0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.
Published: 2021

41. DNA methylation and lipid metabolism:an EWAS of 226 metabolic measures

Author: Gomez-Alonso, M. d. (Monica del C.), Kretschmer, A. (Anja), Wilson, R. (Rory), Pfeiffer, L. (Liliane), Karhunen, V. (Ville), Seppala, I. (Ilkka), Zhang, W. (Weihua), Mittelstrass, K. (Kirstin), Wahl, S. (Simone), Matias-Garcia, P. R. (Pamela R.), Prokisch, H. (Holger), Horn, S. (Sacha), Meitinger, T. (Thomas), Serrano-Garcia, L. R. (Luis R.), Sebert, S. (Sylvain), Raitakari, O. (Olli), Loh, M. (Marie), Rathmann, W. (Wolfgang), Mueller-Nurasyid, M. (Martina), Herder, C. (Christian), Roden, M. (Michael), Hurme, M. (Mikko), Jarvelin, M.-R. (Marjo-Riitta), Ala-Korpela, M. (Mika), Kooner, J. S. (Jaspal S.), Peters, A. (Annette), Lehtimaki, T. (Terho), Chambers, J. C. (John C.), Gieger, C. (Christian), Kettunen, J. (Johannes), Waldenberger, M. (Melanie), Gomez-Alonso, M. d. (Monica del C.), Kretschmer, A. (Anja), Wilson, R. (Rory), Pfeiffer, L. (Liliane), Karhunen, V. (Ville), Seppala, I. (Ilkka), Zhang, W. (Weihua), Mittelstrass, K. (Kirstin), Wahl, S. (Simone), Matias-Garcia, P. R. (Pamela R.), Prokisch, H. (Holger), Horn, S. (Sacha), Meitinger, T. (Thomas), Serrano-Garcia, L. R. (Luis R.), Sebert, S. (Sylvain), Raitakari, O. (Olli), Loh, M. (Marie), Rathmann, W. (Wolfgang), Mueller-Nurasyid, M. (Martina), Herder, C. (Christian), Roden, M. (Michael), Hurme, M. (Mikko), Jarvelin, M.-R. (Marjo-Riitta), Ala-Korpela, M. (Mika), Kooner, J. S. (Jaspal S.), Peters, A. (Annette), Lehtimaki, T. (Terho), Chambers, J. C. (John C.), Gieger, C. (Christian), Kettunen, J. (Johannes), and Waldenberger, M. (Melanie)
Abstract: Background: The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results: We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10⁻¹⁰), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures
Published: 2021

42. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author: Lagou, V, Mägi, R, Hottenga, JJ, Grallert, H, Perry, JR, Bouatia-Naji, N, Marullo, L, Rybin, D, Jansen, R, Min, JL, Dimas, AS, Ulrich, A, Zudina, L, Gådin, JR, Jiang, L, Faggian, A, Bonnefond, A, Fadista, J, Stathopoulou, MG, Isaacs, Aaron, Willems, SM, Navarro, P, Tanaka, T, Jackson, AU, Montasser, ME, O’Connell, JR, Bielak, LF, Webster, RJ, Saxena, R, Stafford, JM, Pourcain, BS, Timpson, NJ, Salo, P, Shin, SY, Amin, Najaf, Smith, AV, Li, G, Verweij, N, Goel, A, Ford, I, Johnson, PCD, Johnson, T, Kapur, K, Thorleifsson, G, Strawbridge, RJ, Rasmussen-Torvik, LJ, Esko, T, Mihailov, E, Fall, T, Fraser, RM, Mahajan, A, Kanoni, S, Giedraitis, V, Kleber, ME, Silbernagel, G, Meyer, J, Müller-Nurasyid, M, Ganna, A, Sarin, AP, Yengo, L, Shungin, D, Luan, J, Horikoshi, M, An, P, Sanna, S, Boettcher, Y, Rayner, NW, Nolte, IM, Zemunik, T, van Iperen, E, Kovacs, P, Hastie, ND, Wild, SH, McLachlan, S, Campbell, S, Polasek, O, Carlson, O, Egan, J, Kiess, W, Willemsen, G, Kuusisto, J, Laakso, M, Dimitriou, M, Hicks, AA, Rauramaa, R, Bandinelli, S, Thorand, B, Liu, Y, Miljkovic, I, Lind, L, Doney, A, Perola, M, Hingorani, A, Kivimaki, M, Kumari, M, Bennett, AJ, Groves, CJ, Herder, C, Koistinen, HA, Kinnunen, L, de Faire, U, Bakker, SJ, Uusitupa, M, Palmer, CN, Jukema, JW, Sattar, N, Pouta, A, Snieder, H, Boerwinkle, E, Pankow, JS, Magnusson, PKE, Krus, U, Scapoli, C, de Geus, EJCN, Blüher, M, Wolffenbuttel, BH, Province, MA, Abecasis, GR, Meigs, JB, Hovingh, GK, Lindström, J, Wilson, JF, Wright, AF, Dedoussis, GVZ, Bornstein, SR, Schwarz, PEH, Tönjes, A, Winkelmann, BR, Boehm, BO, März, W, Metspalu, A, Price, JF, Deloukas, P, Körner, A, Lakka, TA, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Bergman, RN, Tuomilehto, J, Wareham, NJ, Langenberg, C, Männistö, S, Franks, PW, Hayward, C, Vitart, V, Kaprio, J, Visvikis-Siest, S, Balkau, B, Altshuler, D, Rudan, I, Stumvoll, M, Campbell, H, Duijn, Cornelia, Gieger, C, Illig, T, Ferrucci, L, Pedersen, NL, Pramstaller, PP, Boehnke, M, Frayling, TM, Shuldiner, AR, Peyser, PA, Kardia, SL, Palmer, LJ, Penninx, BWJH, Meneton, P, Harris, TB, Navis, G, van der Harst, P, Smith, GD, Forouhi, NG, Loos, RJ, Salomaa, V, Soranzo, N, Boomsma, DI, Groop, L, Tuomi, T, Hofman, Bert, Munroe, PB, Gudnason, V, Siscovick, DS, Watkins, H, Lecoeur, C, Vollenweider, P, Franco-Cereceda, A, Eriksson, P, Jarvelin, M R R, Stefansson, K, Hamsten, A, Nicholson, G, Karpe, F, Dermitzakis, ET, Lindgren, CM, McCarthy, MI, Froguel, P, Kaakinen, MA, Lyssenko, V, Watanabe, RM, Ingelsson, E, Florez, JC, Dupuis, J, Barroso, I, Morris, AP, Prokopenko, I, Lagou, V, Mägi, R, Hottenga, JJ, Grallert, H, Perry, JR, Bouatia-Naji, N, Marullo, L, Rybin, D, Jansen, R, Min, JL, Dimas, AS, Ulrich, A, Zudina, L, Gådin, JR, Jiang, L, Faggian, A, Bonnefond, A, Fadista, J, Stathopoulou, MG, Isaacs, Aaron, Willems, SM, Navarro, P, Tanaka, T, Jackson, AU, Montasser, ME, O’Connell, JR, Bielak, LF, Webster, RJ, Saxena, R, Stafford, JM, Pourcain, BS, Timpson, NJ, Salo, P, Shin, SY, Amin, Najaf, Smith, AV, Li, G, Verweij, N, Goel, A, Ford, I, Johnson, PCD, Johnson, T, Kapur, K, Thorleifsson, G, Strawbridge, RJ, Rasmussen-Torvik, LJ, Esko, T, Mihailov, E, Fall, T, Fraser, RM, Mahajan, A, Kanoni, S, Giedraitis, V, Kleber, ME, Silbernagel, G, Meyer, J, Müller-Nurasyid, M, Ganna, A, Sarin, AP, Yengo, L, Shungin, D, Luan, J, Horikoshi, M, An, P, Sanna, S, Boettcher, Y, Rayner, NW, Nolte, IM, Zemunik, T, van Iperen, E, Kovacs, P, Hastie, ND, Wild, SH, McLachlan, S, Campbell, S, Polasek, O, Carlson, O, Egan, J, Kiess, W, Willemsen, G, Kuusisto, J, Laakso, M, Dimitriou, M, Hicks, AA, Rauramaa, R, Bandinelli, S, Thorand, B, Liu, Y, Miljkovic, I, Lind, L, Doney, A, Perola, M, Hingorani, A, Kivimaki, M, Kumari, M, Bennett, AJ, Groves, CJ, Herder, C, Koistinen, HA, Kinnunen, L, de Faire, U, Bakker, SJ, Uusitupa, M, Palmer, CN, Jukema, JW, Sattar, N, Pouta, A, Snieder, H, Boerwinkle, E, Pankow, JS, Magnusson, PKE, Krus, U, Scapoli, C, de Geus, EJCN, Blüher, M, Wolffenbuttel, BH, Province, MA, Abecasis, GR, Meigs, JB, Hovingh, GK, Lindström, J, Wilson, JF, Wright, AF, Dedoussis, GVZ, Bornstein, SR, Schwarz, PEH, Tönjes, A, Winkelmann, BR, Boehm, BO, März, W, Metspalu, A, Price, JF, Deloukas, P, Körner, A, Lakka, TA, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Bergman, RN, Tuomilehto, J, Wareham, NJ, Langenberg, C, Männistö, S, Franks, PW, Hayward, C, Vitart, V, Kaprio, J, Visvikis-Siest, S, Balkau, B, Altshuler, D, Rudan, I, Stumvoll, M, Campbell, H, Duijn, Cornelia, Gieger, C, Illig, T, Ferrucci, L, Pedersen, NL, Pramstaller, PP, Boehnke, M, Frayling, TM, Shuldiner, AR, Peyser, PA, Kardia, SL, Palmer, LJ, Penninx, BWJH, Meneton, P, Harris, TB, Navis, G, van der Harst, P, Smith, GD, Forouhi, NG, Loos, RJ, Salomaa, V, Soranzo, N, Boomsma, DI, Groop, L, Tuomi, T, Hofman, Bert, Munroe, PB, Gudnason, V, Siscovick, DS, Watkins, H, Lecoeur, C, Vollenweider, P, Franco-Cereceda, A, Eriksson, P, Jarvelin, M R R, Stefansson, K, Hamsten, A, Nicholson, G, Karpe, F, Dermitzakis, ET, Lindgren, CM, McCarthy, MI, Froguel, P, Kaakinen, MA, Lyssenko, V, Watanabe, RM, Ingelsson, E, Florez, JC, Dupuis, J, Barroso, I, Morris, AP, and Prokopenko, I
Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
Published: 2021

43. Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Author: Grosche, S. (Sarah), Marenholz, I. (Ingo), Esparza-Gordillo, J. (Jorge), Arnau-Soler, A. (Aleix), Pairo-Castineira, E. (Erola), Rueschendorf, F. (Franz), Ahluwalia, T. S. (Tarunveer S.), Almqvist, C. (Catarina), Arnold, A. (Andreas), Baurecht, H. (Hansjoerg), Bisgaard, H. (Hans), Bonnelykke, K. (Klaus), Brown, S. J. (Sara J.), Bustamante, M. (Mariona), Curtin, J. A. (John A.), Custovic, A. (Adnan), Dharmage, S. C. (Shyamali C.), Esplugues, A. (Ana), Falchi, M. (Mario), Fernandez-Orth, D. (Dietmar), Ferreira, M. A. (Manuel A. R.), Franke, A. (Andre), Gerdes, S. (Sascha), Gieger, C. (Christian), Hakonarson, H. (Hakon), Holt, P. G. (Patrick G.), Homuth, G. (Georg), Hubner, N. (Norbert), Hysi, P. G. (Pirro G.), Järvelin, M.-R. (Marjo-Riitta), Karlsson, R. (Robert), Koppelman, G. H. (Gerard H.), Lau, S. (Susanne), Lutz, M. (Manuel), Magnusson, P. K. (Patrik K. E.), Marks, G. B. (Guy B.), Mueller-Nurasyid, M. (Martina), Noethen, M. M. (Markus M.), Paternoster, L. (Lavinia), Pennell, C. E. (Craig E.), Peters, A. (Annette), Rawlik, K. (Konrad), Robertson, C. F. (Colin F.), Rodriguez, E. (Elke), Sebert, S. (Sylvain), Simpson, A. (Angela), Sleiman, P. M. (Patrick M. A.), Standl, M. (Marie), Stoelzl, D. (Dora), Strauch, K. (Konstantin), Szwajda, A. (Agnieszka), Tenesa, A. (Albert), Thompson, P. J. (Philip J.), Ullemar, V. (Vilhelmina), Visconti, A. (Alessia), Vonk, J. M. (Judith M.), Wang, C. A. (Carol A.), Weidinger, S. (Stephan), Wielscher, M. (Matthias), Worth, C. L. (Catherine L.), Xu, C.-J. (Chen-Jian), Lee, Y.-A. (Young-Ae), and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Sodium-Hydrogen Exchangers, Genotype, Eczema, Gene Expression, Genetic predisposition to disease, Dual Specificity Phosphatase 1, Rare variants, Matrix Attachment Region Binding Proteins, Polymorphism, Single Nucleotide, Genome-wide association studies, Article, Cytokine Receptor Common beta Subunit, Skin diseases, Rare Diseases, Cardiovascular and Metabolic Diseases, Humans, Receptor, Notch4, Genome-Wide Association Study, Atopic dermatitis
Abstract: Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels. We identify rare exonic variants in DUSP1, NOTCH4, and SLC9A4 to be associated with eczema. In DUSP1 and NOTCH4 missense variants are predicted to impact conserved functional domains. In addition, five novel common variants at SATB1-AS1/KCNH8, TRIB1/LINC00861, ZBTB1, TBX21/OSBPL7, and CSF2RB are discovered. While genes prioritized based on rare variants are significantly up-regulated in the skin, common variants point to immune cell function. Over 20% of the single nucleotide variant-based heritability is attributable to rare and low-frequency variants. The identified rare/low-frequency variants located in functional protein domains point to promising targets for novel therapeutic approaches to eczema., Genetic studies of eczema to date have mostly explored common genetic variation. Here, the authors perform a large meta-analysis for common and rare variants and discover 8 loci associated with eczema. Over 20% of the heritability of the condition is attributable to rare variants.
Published: 2020

44. Host traits, lifestyle and environment are associated with human skin bacteria

Author: Moitinho‐Silva, L., primary, Boraczynski, N., additional, Emmert, H., additional, Baurecht, H., additional, Szymczak, S., additional, Schulz, H., additional, Haller, D., additional, Linseisen, J., additional, Gieger, C., additional, Peters, A., additional, Tittmann, L., additional, Lieb, W., additional, Bang, C., additional, Franke, A., additional, Rodriguez, E., additional, and Weidinger, S., additional
Published: 2021
Full Text: View/download PDF

45. Genetic predisposition to coronary artery disease in type 2 diabetes

Author: van Zuydam, NR, Ladenvall, C, Voight, BF, Strawbridge, RJ, Fernandez Tajes, J, Rayner, NW, Robertson, NR, Mahajan, A, Vlachopoulou, E, Goel, A, Kleber, ME, Nelson, CP, Kwee, LC, Esko, T, Mihailov, E, Mägi, R, Milani, L, Fischer, K, Kanoni, S, Kumar, J, Song, C, Hartiala, JA, Pedersen, NL, Perola, M, Gieger, C, Peters, A, Qu, L, Willems, SM, Doney, ASF, Morris, AD, Zheng, Y, Sesti, G, Hu, FB, Qi, L, Laakso, M, Thorsteinsdottir, U, Grallert, H, van Duijn, C, Reilly, MP, Ingelsson, E, Deloukas, P, Kathiresan, S, Metspalu, A, Shah, SH, Sinisalo, J, Salomaa, V, Hamsten, A, Samani, NJ, März, W, Hazen, SL, and Watkins, H
Abstract: Background - Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes (T2D). Methods - To test whether this reflects differential genetic influences on CAD-risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66,643 subjects (27,708 with CAD and 24,259 with T2D). Variants showing apparent association with CAD in stratified analyses and/or evidence of interaction were evaluated in a further 117,787 subjects (16,694 with CAD and 11,537 with T2D). Results - None of the previously characterised CAD loci was found to have specific effects on CAD in T2D individuals and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. Conclusions - This study found no evidence that the genetic architecture of CAD differs in those with T2D compared to those without T2D.
Published: 2020

46. Identification of Restless Legs Syndrome Genes by Mutational Load Analysis

Author: Tilch, E., Schormair, B., Zhao, C., Salminen, A.V., Nikolic, A., Holzknecht, E., Hogl, B., Poewe, W., Bachmann, C.G., Paulus, W., Trenkwalder, C., Oertel, W.H., Hornyak, M., Fietze, I., Berger, K., Lichtner, P., Gieger, C., Peters, A., Muller-Myhsok, B., Hoischen, A., Winkelmann, J., Oexle, K., Tilch, E., Schormair, B., Zhao, C., Salminen, A.V., Nikolic, A., Holzknecht, E., Hogl, B., Poewe, W., Bachmann, C.G., Paulus, W., Trenkwalder, C., Oertel, W.H., Hornyak, M., Fietze, I., Berger, K., Lichtner, P., Gieger, C., Peters, A., Muller-Myhsok, B., Hoischen, A., Winkelmann, J., and Oexle, K.
Abstract: Contains fulltext : 218278.pdf (Publisher’s version ) (Open Access), OBJECTIVE: Restless legs syndrome is a frequent neurological disorder with substantial burden on individual well-being and public health. Genetic risk loci have been identified, but the causatives genes at these loci are largely unknown, so that functional investigation and clinical translation of molecular research data are still inhibited. To identify putatively causative genes, we searched for highly significant mutational burden in candidate genes. METHODS: We analyzed 84 candidate genes in 4,649 patients and 4,982 controls by next generation sequencing using molecular inversion probes that targeted mainly coding regions. The burden of low-frequency and rare variants was assessed, and in addition, an algorithm (binomial performance deviation analysis) was established to estimate independently the sequence variation in the probe binding regions from the variation in sequencing depth. RESULTS: Highly significant results (considering the number of genes in the genome) of the conventional burden test and the binomial performance deviation analysis overlapped significantly. Fourteen genes were highly significant by one method and confirmed with Bonferroni-corrected significance by the other to show a differential burden of low-frequency and rare variants in restless legs syndrome. Nine of them (AAGAB, ATP2C1, CNTN4, COL6A6, CRBN, GLO1, NTNG1, STEAP4, VAV3) resided in the vicinity of known restless legs syndrome loci, whereas 5 (BBS7, CADM1, CREB5, NRG3, SUN1) have not previously been associated with restless legs syndrome. Burden test and binomial performance deviation analysis also converged significantly in fine-mapping potentially causative domains within these genes. INTERPRETATION: Differential burden with intragenic low-frequency variants reveals putatively causative genes in restless legs syndrome. ANN NEUROL 2020;87:184-193.
Published: 2020

47. Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Author: Van Zuydam, N.R. (Natalie R.), Ladenvall, C. (Claes), Voight, B.F. (Benjamin), Strawbridge, R.J. (Rona), Fernandez-Tajes, J. (Juan), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil R.), Mahajan, A. (Anubha), Vlachopoulou, E. (Efthymia), Goel, A. (Anuj), Kleber, M.E. (Marcus), Nelson, C.P. (Christopher P.), Kwee, L.C. (Lydia Coulter), Esko, T. (Tõnu), Mihailov, E. (Evelin), Mägi, R. (Reedik), Milani, L. (Lili), Fischer, K. (Krista), Kanoni, S. (Stavroula), Kumar, J. (Jitender), Song, C. (Ci), Hartiala, J.A. (Jaana A.), Pedersen, N.L. (Nancy), Perola, M. (Markus), Gieger, C. (Christian), Peters, A. (Annette), Qu, L. (Liming), Willems, S.M. (Sara), Doney, A.S.F. (Alex), Morris, A.D. (Andrew D.), Zheng, Y. (Yan), Sesti, G. (Giorgio), Hu, F.B. (Frank), Qi, L. (Lu), Laakso, M. (Markku), Thorsteinsdottir, U. (Unnur), Grallert, H. (Harald), Duijn, C.M. (Cornelia) van, Reilly, M.P. (Muredach), Ingelsson, E. (Erik), Deloukas, P. (Panos), Kathiresan, S. (Sek), Metspalu, A. (Andres), Shah, S.H. (Svati), Sinisalo, J. (Juha), Salomaa, V. (Veikko), Hamsten, A. (Anders), Samani, N.J. (Nilesh), Ye, S. (Shu), Hazen, S.L. (Stanley), Watkins, H. (Hugh), Saleheen, D. (Danish), Morris, A.P. (Andrew), Colhoun, H.M. (H.), Groop, L. (Leif), McCarthy, M.I. (Mark), Palmer, C.N.A. (Colin), Van Zuydam, N.R. (Natalie R.), Ladenvall, C. (Claes), Voight, B.F. (Benjamin), Strawbridge, R.J. (Rona), Fernandez-Tajes, J. (Juan), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil R.), Mahajan, A. (Anubha), Vlachopoulou, E. (Efthymia), Goel, A. (Anuj), Kleber, M.E. (Marcus), Nelson, C.P. (Christopher P.), Kwee, L.C. (Lydia Coulter), Esko, T. (Tõnu), Mihailov, E. (Evelin), Mägi, R. (Reedik), Milani, L. (Lili), Fischer, K. (Krista), Kanoni, S. (Stavroula), Kumar, J. (Jitender), Song, C. (Ci), Hartiala, J.A. (Jaana A.), Pedersen, N.L. (Nancy), Perola, M. (Markus), Gieger, C. (Christian), Peters, A. (Annette), Qu, L. (Liming), Willems, S.M. (Sara), Doney, A.S.F. (Alex), Morris, A.D. (Andrew D.), Zheng, Y. (Yan), Sesti, G. (Giorgio), Hu, F.B. (Frank), Qi, L. (Lu), Laakso, M. (Markku), Thorsteinsdottir, U. (Unnur), Grallert, H. (Harald), Duijn, C.M. (Cornelia) van, Reilly, M.P. (Muredach), Ingelsson, E. (Erik), Deloukas, P. (Panos), Kathiresan, S. (Sek), Metspalu, A. (Andres), Shah, S.H. (Svati), Sinisalo, J. (Juha), Salomaa, V. (Veikko), Hamsten, A. (Anders), Samani, N.J. (Nilesh), Ye, S. (Shu), Hazen, S.L. (Stanley), Watkins, H. (Hugh), Saleheen, D. (Danish), Morris, A.P. (Andrew), Colhoun, H.M. (H.), Groop, L. (Leif), McCarthy, M.I. (Mark), and Palmer, C.N.A. (Colin)
Abstract: Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
Published: 2020
Full Text: View/download PDF

48. Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data.

Author: English D.R., Southey M.C., Waldenberger M., Milne R.L., Giles G.G., Chambers J.C., Dugue P.-A., Wilson R., Lehne B., Jayasekara H., Wang X., Jung C.-H., Joo J.E., Makalic E., Schmidt D.F., Baglietto L., Severi G., Gieger C., Ladwig K.-H., Peters A., Kooner J.S., English D.R., Southey M.C., Waldenberger M., Milne R.L., Giles G.G., Chambers J.C., Dugue P.-A., Wilson R., Lehne B., Jayasekara H., Wang X., Jung C.-H., Joo J.E., Makalic E., Schmidt D.F., Baglietto L., Severi G., Gieger C., Ladwig K.-H., Peters A., and Kooner J.S.
Abstract: DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10-7, 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P <.05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P <.05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood.Copyright © 2019 Society for the Study of Addiction
Published: 2020

49. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), Codd, V. (Veryan), Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), and Codd, V. (Veryan)
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020
Full Text: View/download PDF

50. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Li, C, Stoma, S, Lotta, LA, Warner, S, Albrecht, E, Allione, A, Arp, PP, Broer, L, Buxton, JL, Alves, ADSC, Deelen, J, Fedko, IO, Gordon, SD, Jiang, T, Karlsson, R, Kerrison, N, Loe, TK, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, JE, Amin, N, Beekman, M, Blakemore, A, Canzian, F, Hamby, SE, Hottenga, J-J, Jones, PD, Jousilahti, P, Magi, R, Medland, SE, Montgomery, GW, Nyholt, DR, Perola, M, Pietilainen, KH, Salomaa, V, Sillanpaa, E, Suchiman, HE, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, JG, Gunter, M, Hagg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, NG, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, NC, Nilsson, P, Ong, KK, Overvad, K, Palli, D, Panico, S, Pedersen, NL, Penninx, BWJH, Ramon Quiros, J, Riitta Jarvelin, M, Rodriguez-Barranco, M, Scott, RA, Severi, G, Slagboom, PE, Spector, TD, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, AG, van der Schouw, YT, van Duijn, CM, Weiderpass, E, Denchi, EL, Matullo, G, Butterworth, AS, Danesh, J, Samani, NJ, Wareham, NJ, Nelson, CP, Langenberg, C, Codd, V, Li, C, Stoma, S, Lotta, LA, Warner, S, Albrecht, E, Allione, A, Arp, PP, Broer, L, Buxton, JL, Alves, ADSC, Deelen, J, Fedko, IO, Gordon, SD, Jiang, T, Karlsson, R, Kerrison, N, Loe, TK, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, JE, Amin, N, Beekman, M, Blakemore, A, Canzian, F, Hamby, SE, Hottenga, J-J, Jones, PD, Jousilahti, P, Magi, R, Medland, SE, Montgomery, GW, Nyholt, DR, Perola, M, Pietilainen, KH, Salomaa, V, Sillanpaa, E, Suchiman, HE, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, JG, Gunter, M, Hagg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, NG, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, NC, Nilsson, P, Ong, KK, Overvad, K, Palli, D, Panico, S, Pedersen, NL, Penninx, BWJH, Ramon Quiros, J, Riitta Jarvelin, M, Rodriguez-Barranco, M, Scott, RA, Severi, G, Slagboom, PE, Spector, TD, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, AG, van der Schouw, YT, van Duijn, CM, Weiderpass, E, Denchi, EL, Matullo, G, Butterworth, AS, Danesh, J, Samani, NJ, Wareham, NJ, Nelson, CP, Langenberg, C, and Codd, V
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

1,233 results on '"Gieger, C."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources