@article {8515,
	title = {{Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls},
	journal = {Nature},
	volume = {570},
	year = {2019},
	month = {06},
	pages = {71{\textendash}76},
	abstract = {Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes (T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5\%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 {\~A}{\textemdash} 10-3) and candidate genes from knockout mice (P = 5.2 {\~A}{\textemdash} 10-3). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25\% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.},
	author = {Flannick, J. and Mercader, J. M. and Fuchsberger, C. and Udler, M. S. and Mahajan, A. and Wessel, J. and Teslovich, T. M. and Caulkins, L. and Koesterer, R. and Barajas-Olmos, F. and Blackwell, T. W. and Boerwinkle, E. and Brody, J. A. and Centeno-Cruz, F. and Chen, L. and Chen, S. and Contreras-Cubas, C. and C?rdova, E. and Correa, A. and Cortes, M. and DeFronzo, R. A. and Dolan, L. and Drews, K. L. and Elliott, A. and Floyd, J. S. and Gabriel, S. and Garay-Sevilla, M. E. and Garc?a-Ortiz, H. and Gross, M. and Han, S. and Heard-Costa, N. L. and Jackson, A. U. and J?rgensen, M. E. and Kang, H. M. and Kelsey, M. and Kim, B. J. and Koistinen, H. A. and Kuusisto, J. and Leader, J. B. and Linneberg, A. and Liu, C. T. and Liu, J. and Lyssenko, V. and Manning, A. K. and Marcketta, A. and Malacara-Hernandez, J. M. and Mart?nez-Hern?ndez, A. and Matsuo, K. and Mayer-Davis, E. and Mendoza-Caamal, E. and Mohlke, K. L. and Morrison, A. C. and Ndungu, A. and Ng, M. C. Y. and O{\textquoteright}Dushlaine, C. and Payne, A. J. and Pihoker, C. and Post, W. S. and Preuss, M. and Psaty, B. M. and Vasan, R. S. and Rayner, N. W. and Reiner, A. P. and Revilla-Monsalve, C. and Robertson, N. R. and Santoro, N. and Schurmann, C. and So, W. Y. and Sober?n, X. and Stringham, H. M. and Strom, T. M. and Tam, C. H. T. and Thameem, F. and Tomlinson, B. and Torres, J. M. and Tracy, R. P. and van Dam, R. M. and Vujkovic, M. and Wang, S. and Welch, R. P. and Witte, D. R. and Wong, T. Y. and Atzmon, G. and Barzilai, N. and Blangero, J. and Bonnycastle, L. L. and Bowden, D. W. and Chambers, J. C. and Chan, E. and Cheng, C. Y. and Cho, Y. S. and Collins, F. S. and de Vries, P. S. and Duggirala, R. and Glaser, B. and Gonzalez, C. and Gonzalez, M. E. and Groop, L. and Kooner, J. S. and Kwak, S. H. and Laakso, M. and Lehman, D. M. and Nilsson, P. and Spector, T. D. and Tai, E. S. and Tuomi, T. and Tuomilehto, J. and Wilson, J. G. and Aguilar-Salinas, C. A. and Bottinger, E. and Burke, B. and Carey, D. J. and Chan, J. C. N. and Dupuis, J. and Frossard, P. and Heckbert, S. R. and Hwang, M. Y. and Kim, Y. J. and Kirchner, H. L. and Lee, J. Y. and Lee, J. and Loos, R. J. F. and Ma, R. C. W. and Morris, A. D. and O{\textquoteright}Donnell, C. J. and Palmer, C. N. A. and Pankow, J. and Park, K. S. and Rasheed, A. and Saleheen, D. and Sim, X. and Small, K. S. and Teo, Y. Y. and Haiman, C. and Hanis, C. L. and Henderson, B. E. and Orozco, L. and Tusi?-Luna, T. and Dewey, F. E. and Baras, A. and Gieger, C. and Meitinger, T. and Strauch, K. and Lange, L. and Grarup, N. and Hansen, T. and Pedersen, O. and Zeitler, P. and Dabelea, D. and Abecasis, G. and Bell, G. I. and Cox, N. J. and Seielstad, M. and Sladek, R. and Meigs, J. B. and Rich, S. S. and Rotter, J. I. and Altshuler, D. and Burtt, N. P. and Scott, L. J. and Morris, A. P. and Florez, J. C. and McCarthy, M. I. and Boehnke, M.}
}
@article {8518,
	title = {{Genome-Wide Association Study of Apparent Treatment-Resistant Hypertension in the CHARGE Consortium: The CHARGE Pharmacogenetics Working Group},
	journal = {Am J Hypertens},
	volume = {32},
	year = {2019},
	month = {11},
	pages = {1146{\textendash}1153},
	abstract = {{Only a handful of genetic discovery efforts in apparent treatment-resistant hypertension (aTRH) have been described.\ We conducted a case-control genome-wide association study of aTRH among persons treated for hypertension, using data from 10 cohorts of European ancestry (EA) and 5 cohorts of African ancestry (AA). Cases were treated with 3 different antihypertensive medication classes and had blood pressure (BP) above goal (systolic BP {\^a}{\textperthousand}{\textyen} 140 mm Hg and/or diastolic BP {\^a}{\textperthousand}{\textyen} 90 mm Hg) or 4 or more medication classes regardless of BP control (nEA = 931},
	author = {Irvin, M. R. and Sitlani, C. M. and Floyd, J. S. and Psaty, B. M. and Bis, J. C. and Wiggins, K. L. and Whitsel, E. A. and Sturmer, T. and Stewart, J. and Raffield, L. and Sun, F. and Liu, C. T. and Xu, H. and Cupples, A. L. and Tanner, R. M. and Rossing, P. and Smith, A. and Zilh?o, N. R. and Launer, L. J. and Noordam, R. and Rotter, J. I. and Yao, J. and Li, X. and Guo, X. and Limdi, N. and Sundaresan, A. and Lange, L. and Correa, A. and Stott, D. J. and Ford, I. and Jukema, J. W. and Gudnason, V. and Mook-Kanamori, D. O. and Trompet, S. and Palmas, W. and Warren, H. R. and Hellwege, J. N. and Giri, A. and O{\textquoteright}Donnell, C. and Hung, A. M. and Edwards, T. L. and Ahluwalia, T. S. and Arnett, D. K. and Avery, C. L.}
}
@article {9181,
	title = {{Clonal hematopoiesis of indeterminate potential, DNA methylation, and risk for coronary artery disease},
	journal = {Nat Commun},
	volume = {13},
	year = {2022},
	month = {Sep},
	pages = {5350},
	abstract = {Age-related changes to the genome-wide DNA methylation (DNAm) pattern observed in blood are well-documented. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by the age-related acquisition and expansion of leukemogenic mutations in hematopoietic stem cells (HSCs), is associated with blood cancer and coronary artery disease (CAD). Epigenetic regulators DNMT3A and TET2 are the two most frequently mutated CHIP genes. Here, we present results from an epigenome-wide association study for CHIP in 582 Cardiovascular Health Study (CHS) participants, with replication in 2655 Atherosclerosis Risk in Communities (ARIC) Study participants. We show that DNMT3A and TET2 CHIP have distinct and directionally opposing genome-wide DNAm association patterns consistent with their regulatory roles, albeit both promoting self-renewal of HSCs. Mendelian randomization analyses indicate that a subset of DNAm alterations associated with these two leading CHIP genes may promote the risk for CAD.},
	author = {Uddin, M. D. M. and Nguyen, N. Q. H. and Yu, B. and Brody, J. A. and Pampana, A. and Nakao, T. and Fornage, M. and Bressler, J. and Sotoodehnia, N. and Weinstock, J. S. and Honigberg, M. C. and Nachun, D. and Bhattacharya, R. and Griffin, G. K. and Chander, V. and Gibbs, R. A. and Rotter, J. I. and Liu, C. and Baccarelli, A. A. and Chasman, D. I. and Whitsel, E. A. and Kiel, D. P. and Murabito, J. M. and Boerwinkle, E. and Ebert, B. L. and Jaiswal, S. and Floyd, J. S. and Bick, A. G. and Ballantyne, C. M. and Psaty, B. M. and Natarajan, P. and Conneely, K. N.}
}
@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.}
}
