@article {8566,
	title = {{Gene-gene Interaction Analyses for Atrial Fibrillation},
	journal = {Sci Rep},
	volume = {6},
	year = {2016},
	month = {11},
	pages = {35371},
	abstract = {{Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95\% CI: 1.27-1.65},
	author = {Lin, H. and Mueller-Nurasyid, M. and Smith, A. V. and Arking, D. E. and Barnard, J. and Bartz, T. M. and Lunetta, K. L. and Lohman, K. and Kleber, M. E. and Lubitz, S. A. and Geelhoed, B. and Trompet, S. and Niemeijer, M. N. and Kacprowski, T. and Chasman, D. I. and Klarin, D. and Sinner, M. F. and Waldenberger, M. and Meitinger, T. and Harris, T. B. and Launer, L. J. and Soliman, E. Z. and Chen, L. Y. and Smith, J. D. and Van Wagoner, D. R. and Rotter, J. I. and Psaty, B. M. and Xie, Z. and Hendricks, A. E. and Ding, J. and Delgado, G. E. and Verweij, N. and van der Harst, P. and Macfarlane, P. W. and Ford, I. and Hofman, A. and Uitterlinden, A. and Heeringa, J. and Franco, O. H. and Kors, J. A. and Weiss, S. and V?lzke, H. and Rose, L. M. and Natarajan, P. and Kathiresan, S. and K??b, S. and Gudnason, V. and Alonso, A. and Chung, M. K. and Heckbert, S. R. and Benjamin, E. J. and Liu, Y. and M?rz, W. and Rienstra, M. and Jukema, J. W. and Stricker, B. H. and D?rr, M. and Albert, C. M. and Ellinor, P. T.}
}
@article {8517,
	title = {{Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry},
	journal = {J Bone Miner Res},
	volume = {34},
	year = {2019},
	month = {07},
	pages = {1284{\textendash}1296},
	abstract = {Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with {\^a}{\textasciicircum}{\textonequarter}2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p {\^a}{\textperthousand}¤ 2.6 {\~A}{\textemdash} 10-8 ) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 {\~A}{\textemdash} 10-5 ). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12\% to 22\% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. {\^A}{\textcopyright} 2019 American Society for Bone and Mineral Research.},
	author = {Hsu, Y. H. and Estrada, K. and Evangelou, E. and Ackert-Bicknell, C. and Akesson, K. and Beck, T. and Brown, S. J. and Capellini, T. and Carbone, L. and Cauley, J. and Cheung, C. L. and Cummings, S. R. and Czerwinski, S. and Demissie, S. and Econs, M. and Evans, D. and Farber, C. and Gautvik, K. and Harris, T. and Kammerer, C. and Kemp, J. and Koller, D. L. and Kung, A. and Lawlor, D. and Lee, M. and Lorentzon, M. and McGuigan, F. and Medina-Gomez, C. and Mitchell, B. and Newman, A. and Nielson, C. and Ohlsson, C. and Peacock, M. and Reppe, S. and Richards, J. B. and Robbins, J. and Sigurdsson, G. and Spector, T. D. and Stefansson, K. and Streeten, E. and Styrkarsdottir, U. and Tobias, J. and Trajanoska, K. and Uitterlinden, A. and Vandenput, L. and Wilson, S. G. and Yerges-Armstrong, L. and Young, M. and Zillikens, M. C. and Rivadeneira, F. and Kiel, D. P. and Karasik, D.}
}
@article {8781,
	title = {{A multi-ethnic epigenome-wide association study of leukocyte DNA methylation and blood lipids},
	journal = {Nat Commun},
	volume = {12},
	year = {2021},
	month = {06},
	pages = {3987},
	abstract = {10.1038/s41467-021-23899-yHere we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups.},
	author = {Jhun, M. A. and Mendelson, M. and Wilson, R. and Gondalia, R. and Joehanes, R. and Salfati, E. and Zhao, X. and Braun, K. V. E. and Do, A. N. and Hedman, {\r A}. K. and Zhang, T. and Carnero-Montoro, E. and Shen, J. and Bartz, T. M. and Brody, J. A. and Montasser, M. E. and O{\textquoteright}Connell, J. R. and Yao, C. and Xia, R. and Boerwinkle, E. and Grove, M. and Guan, W. and Liliane, P. and Singmann, P. and M{\"u}ller-Nurasyid, M. and Meitinger, T. and Gieger, C. and Peters, A. and Zhao, W. and Ware, E. B. and Smith, J. A. and Dhana, K. and van Meurs, J. and Uitterlinden, A. and Ikram, M. A. and Ghanbari, M. and Zhi, D. and Gustafsson, S. and Lind, L. and Li, S. and Sun, D. and Spector, T. D. and Chen, Y. I. and Damcott, C. and Shuldiner, A. R. and Absher, D. M. and Horvath, S. and Tsao, P. S. and Kardia, S. and Psaty, B. M. and Sotoodehnia, N. and Bell, J. T. and Ingelsson, E. and Chen, W. and Dehghan, A. and Arnett, D. K. and Waldenberger, M. and Hou, L. and Whitsel, E. A. and Baccarelli, A. and Levy, D. and Fornage, M. and Irvin, M. R. and Assimes, T. L.}
}
@article {8772,
	title = {{The trans-ancestral genomic architecture of glycemic traits},
	journal = {Nat Genet},
	volume = {53},
	year = {2021},
	month = {06},
	pages = {840{\textendash}860},
	abstract = {10.1038/s41588-021-00852-9Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30\% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 {\texttimes} 10-8), 80\% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99\% credible sets by a median of 37.5\%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.},
	author = {Chen, J. and Spracklen, C. N. and Marenne, G. and Varshney, A. and Corbin, L. J. and Luan, J. and Willems, S. M. and Wu, Y. and Zhang, X. and Horikoshi, M. and Boutin, T. S. and M{\"a}gi, R. and Waage, J. and Li-Gao, R. and Chan, K. H. K. and Yao, J. and Anasanti, M. D. and Chu, A. Y. and Claringbould, A. and Heikkinen, J. and Hong, J. and Hottenga, J. J. and Huo, S. and Kaakinen, M. A. and Louie, T. and M{\"a}rz, W. and Moreno-Macias, H. and Ndungu, A. and Nelson, S. C. and Nolte, I. M. and North, K. E. and Raulerson, C. K. and Ray, D. and Rohde, R. and Rybin, D. and Schurmann, C. and Sim, X. and Southam, L. and Stewart, I. D. and Wang, C. A. and Wang, Y. and Wu, P. and Zhang, W. and Ahluwalia, T. S. and Appel, E. V. R. and Bielak, L. F. and Brody, J. A. and Burtt, N. P. and Cabrera, C. P. and Cade, B. E. and Chai, J. F. and Chai, X. and Chang, L. C. and Chen, C. H. and Chen, B. H. and Chitrala, K. N. and Chiu, Y. F. and de Haan, H. G. and Delgado, G. E. and Demirkan, A. and Duan, Q. and Engmann, J. and Fatumo, S. A. and Gay{\'a}n, J. and Giulianini, F. and Gong, J. H. and Gustafsson, S. and Hai, Y. and Hartwig, F. P. and He, J. and Heianza, Y. and Huang, T. and Huerta-Chagoya, A. and Hwang, M. Y. and Jensen, R. A. and Kawaguchi, T. and Kentistou, K. A. and Kim, Y. J. and Kleber, M. E. and Kooner, I. K. and Lai, S. and Lange, L. A. and Langefeld, C. D. and Lauzon, M. and Li, M. and Ligthart, S. and Liu, J. and Loh, M. and Long, J. and Lyssenko, V. and Mangino, M. and Marzi, C. and Montasser, M. E. and Nag, A. and Nakatochi, M. and Noce, D. and Noordam, R. and Pistis, G. and Preuss, M. and Raffield, L. and Rasmussen-Torvik, L. J. and Rich, S. S. and Robertson, N. R. and Rueedi, R. and Ryan, K. and Sanna, S. and Saxena, R. and Schraut, K. E. and Sennblad, B. and Setoh, K. and Smith, A. V. and Spars{\o}, T. and Strawbridge, R. J. and Takeuchi, F. and Tan, J. and Trompet, S. and van den Akker, E. and van der Most, P. J. and Verweij, N. and Vogel, M. and Wang, H. and Wang, C. and Wang, N. and Warren, H. R. and Wen, W. and Wilsgaard, T. and Wong, A. and Wood, A. R. and Xie, T. and Zafarmand, M. H. and Zhao, J. H. and Zhao, W. and Amin, N. and Arzumanyan, Z. and Astrup, A. and Bakker, S. J. L. and Baldassarre, D. and Beekman, M. and Bergman, R. N. and Bertoni, A. and Bl{\"u}her, M. and Bonnycastle, L. L. and Bornstein, S. R. and Bowden, D. W. and Cai, Q. and Campbell, A. and Campbell, H. and Chang, Y. C. and de Geus, E. J. C. and Dehghan, A. and Du, S. and Eiriksdottir, G. and Farmaki, A. E. and Fr{\r a}nberg, M. and Fuchsberger, C. and Gao, Y. and Gjesing, A. P. and Goel, A. and Han, S. and Hartman, C. A. and Herder, C. and Hicks, A. A. and Hsieh, C. H. and Hsueh, W. A. and Ichihara, S. and Igase, M. and Ikram, M. A. and Johnson, W. C. and J{\o}rgensen, M. E. and Joshi, P. K. and Kalyani, R. R. and Kandeel, F. R. and Katsuya, T. and Khor, C. C. and Kiess, W. and Kolcic, I. and Kuulasmaa, T. and Kuusisto, J. and L{\"a}ll, K. and Lam, K. and Lawlor, D. A. and Lee, N. R. and Lemaitre, R. N. and Li, H. and Lin, S. Y. and Lindstr{\"o}m, J. and Linneberg, A. and Liu, J. and Lorenzo, C. and Matsubara, T. and Matsuda, F. and Mingrone, G. and Mooijaart, S. and Moon, S. and Nabika, T. and Nadkarni, G. N. and Nadler, J. L. and Nelis, M. and Neville, M. J. and Norris, J. M. and Ohyagi, Y. and Peters, A. and Peyser, P. A. and Polasek, O. and Qi, Q. and Raven, D. and Reilly, D. F. and Reiner, A. and Rivideneira, F. and Roll, K. and Rudan, I. and Sabanayagam, C. and Sandow, K. and Sattar, N. and Sch{\"u}rmann, A. and Shi, J. and Stringham, H. M. and Taylor, K. D. and Teslovich, T. M. and Thuesen, B. and Timmers, P. R. H. J. and Tremoli, E. and Tsai, M. Y. and Uitterlinden, A. and van Dam, R. M. and van Heemst, D. and van Hylckama Vlieg, A. and Van Vliet-Ostaptchouk, J. V. and Vangipurapu, J. and Vestergaard, H. and Wang, T. and Willems van Dijk, K. and Zemunik, T. and Abecasis, G. R. and Adair, L. S. and Aguilar-Salinas, C. A. and Alarc{\'o}n-Riquelme, M. E. and An, P. and Aviles-Santa, L. and Becker, D. M. and Beilin, L. J. and Bergmann, S. and Bisgaard, H. and Black, C. and Boehnke, M. and Boerwinkle, E. and B{\"o}hm, B. O. and B{\o}nnelykke, K. and Boomsma, D. I. and Bottinger, E. P. and Buchanan, T. A. and Canouil, M. and Caulfield, M. J. and Chambers, J. C. and Chasman, D. I. and Chen, Y. I. and Cheng, C. Y. and Collins, F. S. and Correa, A. and Cucca, F. and de Silva, H. J. and Dedoussis, G. and Elmst{\r a}hl, S. and Evans, M. K. and Ferrannini, E. and Ferrucci, L. and Florez, J. C. and Franks, P. W. and Frayling, T. M. and Froguel, P. and Gigante, B. and Goodarzi, M. O. and Gordon-Larsen, P. and Grallert, H. and Grarup, N. and Grimsgaard, S. and Groop, L. and Gudnason, V. and Guo, X. and Hamsten, A. and Hansen, T. and Hayward, C. and Heckbert, S. R. and Horta, B. L. and Huang, W. and Ingelsson, E. and James, P. S. and Jarvelin, M. R. and Jonas, J. B. and Jukema, J. W. and Kaleebu, P. and Kaplan, R. and Kardia, S. L. R. and Kato, N. and Keinanen-Kiukaanniemi, S. M. and Kim, B. J. and Kivimaki, M. and Koistinen, H. A. and Kooner, J. S. and K{\"o}rner, A. and Kovacs, P. and Kuh, D. and Kumari, M. and Kutalik, Z. and Laakso, M. and Lakka, T. A. and Launer, L. J. and Leander, K. and Li, H. and Lin, X. and Lind, L. and Lindgren, C. and Liu, S. and Loos, R. J. F. and Magnusson, P. K. E. and Mahajan, A. and Metspalu, A. and Mook-Kanamori, D. O. and Mori, T. A. and Munroe, P. B. and Nj{\o}lstad, I. and O{\textquoteright}Connell, J. R. and Oldehinkel, A. J. and Ong, K. K. and Padmanabhan, S. and Palmer, C. N. A. and Palmer, N. D. and Pedersen, O. and Pennell, C. E. and Porteous, D. J. and Pramstaller, P. P. and Province, M. A. and Psaty, B. M. and Qi, L. and Raffel, L. J. and Rauramaa, R. and Redline, S. and Ridker, P. M. and Rosendaal, F. R. and Saaristo, T. E. and Sandhu, M. and Saramies, J. and Schneiderman, N. and Schwarz, P. and Scott, L. J. and Selvin, E. and Sever, P. and Shu, X. O. and Slagboom, P. E. and Small, K. S. and Smith, B. H. and Snieder, H. and Sofer, T. and S{\o}rensen, T. I. A. and Spector, T. D. and Stanton, A. and Steves, C. J. and Stumvoll, M. and Sun, L. and Tabara, Y. and Tai, E. S. and Timpson, N. J. and Tonjes, A. and Tuomilehto, J. and Tusie, T. and Uusitupa, M. and van der Harst, P. and van Duijn, C. and Vitart, V. and Vollenweider, P. and Vrijkotte, T. G. M. and Wagenknecht, L. E. and Walker, M. and Wang, Y. X. and Wareham, N. J. and Watanabe, R. M. and Watkins, H. and Wei, W. B. and Wickremasinghe, A. R. and Willemsen, G. and Wilson, J. F. and Wong, T. Y. and Wu, J. Y. and Xiang, A. H. and Yanek, L. R. and Yengo, L. and Yokota, M. and Zeggini, E. and Zheng, W. and Zonderman, A. B. and Rotter, J. I. and Gloyn, A. L. and McCarthy, M. I. and Dupuis, J. and Meigs, J. B. and Scott, R. A. and Prokopenko, I. and Leong, A. and Liu, C. T. and Parker, S. C. J. and Mohlke, K. L. and Langenberg, C. and Wheeler, E. and Morris, A. P. and Barroso, I. and de Haan, H. G. and van den Akker, E. and van der Most, P. J. and de Geus, E. J. C. and van Dam, R. M. and van Heemst, D. and van Hylckama Vlieg, A. and van Willems van Dijk, K. and de Silva, H. J. and van der Harst, P. and van Duijn, C.}
}
@article {9186,
	title = {{Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways},
	journal = {Nat Commun},
	volume = {13},
	year = {2022},
	month = {09},
	pages = {5144},
	abstract = {250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.},
	author = {Young, W. J. and Lahrouchi, N. and Isaacs, A. and Duong, T. and Foco, L. and Ahmed, F. and Brody, J. A. and Salman, R. and Noordam, R. and Benjamins, J. W. and Haessler, J. and Lyytik{\"a}inen, L. P. and Repetto, L. and Concas, M. P. and van den Berg, M. E. and Weiss, S. and Baldassari, A. R. and Bartz, T. M. and Cook, J. P. and Evans, D. S. and Freudling, R. and Hines, O. and Isaksen, J. L. and Lin, H. and Mei, H. and Moscati, A. and M{\"u}ller-Nurasyid, M. and Nursyifa, C. and Qian, Y. and Richmond, A. and Roselli, C. and Ryan, K. A. and Tarazona-Santos, E. and Th{\'e}riault, S. and van Duijvenboden, S. and Warren, H. R. and Yao, J. and Raza, D. and Aeschbacher, S. and Ahlberg, G. and Alonso, A. and Andreasen, L. and Bis, J. C. and Boerwinkle, E. and Campbell, A. and Catamo, E. and Cocca, M. and Cutler, M. J. and Darbar, D. and De Grandi, A. and De Luca, A. and Ding, J. and Ellervik, C. and Ellinor, P. T. and Felix, S. B. and Froguel, P. and Fuchsberger, C. and G{\"o}gele, M. and Graff, C. and Graff, M. and Guo, X. and Hansen, T. and Heckbert, S. R. and Huang, P. L. and Huikuri, H. V. and Hutri-K{\"a}h{\"o}nen, N. and Ikram, M. A. and Jackson, R. D. and Junttila, J. and Kavousi, M. and Kors, J. A. and Leal, T. P. and Lemaitre, R. N. and Lin, H. J. and Lind, L. and Linneberg, A. and Liu, S. and Macfarlane, P. W. and Mangino, M. and Meitinger, T. and Mezzavilla, M. and Mishra, P. P. and Mitchell, R. N. and Mononen, N. and Montasser, M. E. and Morrison, A. C. and Nauck, M. and Nauffal, V. and Navarro, P. and Nikus, K. and Pare, G. and Patton, K. K. and Pelliccione, G. and Pittman, A. and Porteous, D. J. and Pramstaller, P. P. and Preuss, M. H. and Raitakari, O. T. and Reiner, A. P. and Ribeiro, A. L. P. and Rice, K. M. and Risch, L. and Schlessinger, D. and Schotten, U. and Schurmann, C. and Shen, X. and Shoemaker, M. B. and Sinagra, G. and Sinner, M. F. and Soliman, E. Z. and Stoll, M. and Strauch, K. and Tarasov, K. and Taylor, K. D. and Tinker, A. and Trompet, S. and Uitterlinden, A. and V{\"o}lker, U. and V{\"o}lzke, H. and Waldenberger, M. and Weng, L. C. and Whitsel, E. A. and Wilson, J. G. and Avery, C. L. and Conen, D. and Correa, A. and Cucca, F. and D{\"o}rr, M. and Gharib, S. A. and Girotto, G. and Grarup, N. and Hayward, C. and Jamshidi, Y. and Jarvelin, M. R. and Jukema, J. W. and K{\"a}{\"a}b, S. and K{\"a}h{\"o}nen, M. and Kanters, J. K. and Kooperberg, C. and Lehtim{\"a}ki, T. and Lima-Costa, M. F. and Liu, Y. and Loos, R. J. F. and Lubitz, S. A. and Mook-Kanamori, D. O. and Morris, A. P. and O{\textquoteright}Connell, J. R. and Olesen, M. S. and Orini, M. and Padmanabhan, S. and Pattaro, C. and Peters, A. and Psaty, B. M. and Rotter, J. I. and Stricker, B. and van der Harst, P. and van Duijn, C. M. and Verweij, N. and Wilson, J. F. and Arking, D. E. and Ramirez, J. and Lambiase, P. D. and Sotoodehnia, N. and Mifsud, B. and Newton-Cheh, C. and Munroe, P. B.}
}
@article {8982,
	title = {{Obesity Partially Mediates the Diabetogenic Effect of Lowering LDL Cholesterol},
	journal = {Diabetes Care},
	volume = {45},
	year = {2022},
	month = {Jan},
	pages = {232{\textendash}240},
	abstract = {LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown.\ We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,908 participants to investigate the effect of lowering LDLc on type 2 diabetes risk and the proportion of this effect mediated through BMI. We used data from 92,532 participants from 14 observational studies to replicate findings in individual-level MR analyses.\ A 1-SD decrease in genetically predicted LDLc was associated with increased type 2 diabetes odds (odds ratio [OR] 1.12 [95\% CI 1.01, 1.24]) and BMI (β = 0.07 SD units [95\% CI 0.02, 0.12]) in univariable MR analyses. The multivariable MR analysis showed evidence of an indirect effect of lowering LDLc on type 2 diabetes through BMI (OR 1.04 [95\% CI 1.01, 1.08]) with a proportion mediated of 38\% of the total effect (P = 0.03). Total and indirect effect estimates were similar across a number of sensitivity analyses. Individual-level MR analyses confirmed the indirect effect of lowering LDLc on type 2 diabetes through BMI with an estimated proportion mediated of 8\% (P = 0.04).\ These findings suggest that the diabetogenic effect attributed to lowering LDLc is partially mediated through increased BMI. Our results could help advance understanding of adipose tissue and lipids in type 2 diabetes pathophysiology and inform strategies to reduce diabetes risk among individuals taking LDLc-lowering medications.},
	author = {Wu, P. and Moon, J. Y. and Daghlas, I. and Franco, G. and Porneala, B. C. and Ahmadizar, F. and Richardson, T. G. and Isaksen, J. L. and Hindy, G. and Yao, J. and Sitlani, C. M. and Raffield, L. M. and Yanek, L. R. and Feitosa, M. F. and Cuadrat, R. R. C. and Qi, Q. and Arfan Ikram, M. and Ellervik, C. and Ericson, U. and Goodarzi, M. O. and Brody, J. A. and Lange, L. and Mercader, J. M. and Vaidya, D. and An, P. and Schulze, M. B. and Masana, L. and Ghanbari, M. and Olesen, M. S. and Cai, J. and Guo, X. and Floyd, J. S. and J{\"a}ger, S. and Province, M. A. and Kalyani, R. R. and Psaty, B. M. and Orho-Melander, M. and Ridker, P. M. and Kanters, J. K. and Uitterlinden, A. and Davey Smith, G. and Gill, D. and Kaplan, R. C. and Kavousi, M. and Raghavan, S. and Chasman, D. I. and Rotter, J. I. and Meigs, J. B. and Florez, J. C. and Dupuis, J. and Liu, C. T. and Merino, J.}
}
