Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program

被引：38

作者：

Verma, Anurag ^{[1
,2
,3
]}

Huffman, Jennifer E. ^{[4
,5
,6
]}

Rodriguez, Alex ^{[7
]}

Conery, Mitchell ^{[8
]}

Liu, Molei ^{[9
]}

Ho, Yuk-Lam ^{[4
]}

Kim, Youngdae ^{[10
]}

Heise, David A. ^{[11
]}

Guare, Lindsay ^{[2
]}

Panickan, Vidul Ayakulangara ^{[12
]}

Garcon, Helene ^{[4
]}

Linares, Franciel ^{[13
]}

Costa, Lauren ^{[14
]}

Goethert, Ian ^{[15
]}

Tipton, Ryan ^{[16
]}

Honerlaw, Jacqueline ^{[4
]}

Davies, Laura ^{[17
]}

Whitbourne, Stacey ^{[6
,14
,18
]}

Cohen, Jeremy ^{[11
]}

Posner, Daniel C. ^{[4
]}

Sangar, Rahul ^{[14
]}

Murray, Michael ^{[14
]}

Wang, Xuan ^{[12
,19
]}

Dochtermann, Daniel R. ^{[20
]}

Devineni, Poornima ^{[20
]}

Shi, Yunling ^{[20
]}

Nandi, Tarak Nath ^{[7
]}

Assimes, Themistocles L. ^{[21
]}

Brunette, Charles A. ^{[6
,22
]}

Carroll, Robert J. ^{[23
]}

Clifford, Royce ^{[24
,25
]}

Duvall, Scott ^{[26
,27
]}

Gelernter, Joel ^{[28
,29
]}

Hung, Adriana ^{[30
,31
]}

Iyengar, Sudha K. ^{[32
,33
,34
,35
]}

Joseph, Jacob ^{[36
,37
]}

Kember, Rachel ^{[38
,39
]}

Kranzler, Henry ^{[38
,39
]}

Kripke, Colleen M. ^{[2
]}

Levey, Daniel ^{[28
,40
]}

Luoh, Shiuh-Wen ^{[41
,42
]}

Merritt, Victoria C. ^{[24
]}

Overstreet, Cassie ^{[28
]}

Deak, Joseph D. ^{[43
,44
]}

Grant, Struan F. A. ^{[45
,46
,47
,48
]}

Polimanti, Renato ^{[43
]}

Roussos, Panos ^{[49
,50
]}

Shakt, Gabrielle ^{[1
,51
]}

Sun, Yan V. ^{[52
]}

Tsao, Noah ^{[1
,51
]}

机构：

[1] Corporal Michael Crescenz VA Med Ctr, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA

[3] Univ Penn, Inst Biomed Informat, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MAV, Boston, MA 02130 USA

[5] Palo Alto Hlth Care Syst, Palo Alto Vet Inst Res PAVIR, Palo Alto, CA 94304 USA

[6] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[7] Argonne Natl Lab, Data Sci & Learning, Lemont, IL 60439 USA

[8] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA

[9] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY 10032 USA

[10] Argonne Natl Lab, Math & Comp Sci Div, Lemont, IL 60439 USA

[11] Oak Ridge Natl Lab, Dept Energy, Cyber Resilience & Intelligence Div, Natl Secur Sci Directorate, Oak Ridge, TN 37831 USA

[12] Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA

[13] Oak Ridge Natl Lab, Dept Energy, Informat Technol Serv Directorate, R&D Syst Engn, Oak Ridge, TN 37831 USA

[14] VA Boston Healthcare Syst, MVP Boston Coordinating Ctr, Boston, MA 02111 USA

[15] Oak Ridge Natl Lab, Dept Energy, Informat Technol Serv Div, Data Management & Engn, Oak Ridge, TN 37831 USA

[16] Oak Ridge Natl Lab, Dept Energy, Informat Technol Serv Div, Knowledge Discovery Infrastruct, Oak Ridge, TN 37831 USA

[17] Oak Ridge Natl Lab, Dept Energy, Comp & Computat Sci Dir PMO, PMO, Oak Ridge, TN 37831 USA

[18] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA

[19] Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT 84112 USA

[20] VA Boston Healthcare Syst, VA Cooperat Studies Program, Boston, MA 02130 USA

[21] VA Palo Alto Healthcare Syst, Med Cardiol, Palo Alto, CA 94304 USA

[22] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA

[23] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN 37211 USA

[24] VA San Diego Healthcare Syst, Res Dept, San Diego, CA 92161 USA

[25] UCSD San Diego, Dept Otolaryngol, La Jolla, CA 92093 USA

[26] VA Salt Lake City Hlth Care Syst, VA Informat & Comp Infrastruct, Salt Lake City, UT 84148 USA

[27] Univ Utah, Sch Med, Internal Med Epidemiol, Salt Lake City, UT 84132 USA

[28] Yale Univ, Psychiat Human Genet, New Haven, CT 06520 USA

[29] VA Connecticut Healthcare Syst West Haven, West Haven, CT 06516 USA

[30] VA Tennessee Valley Healthcare Syst, Med Nephrol & Hypertens, Nashville, TN 37232 USA

[31] Vanderbilt Univ, Nashville, TN 37232 USA

[32] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA

[33] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA

[34] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA

[35] Case Western Reserve Univ, Cleveland Inst Computat Biol, Cleveland, OH 44106 USA

[36] VA Providence Healthcare Syst, Med Cardiol Sect, Providence, RI 02908 USA

[37] Brown Univ, Dept Med, Providence, RI 02908 USA

[38] Corporal Michael Crescenz VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA

[39] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA

[40] VA Connecticut Healthcare Syst West Haven, Med, West Haven, CT 06516 USA

[41] VA Portland Hlth Care Syst, Portland, OR 97239 USA

[42] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97239 USA

[43] Yale Univ, Psychiat, New Haven, CT 06520 USA

[44] VA Connecticut Healthcare Syst West Haven, Psychiat, West Haven, CT 06516 USA

[45] Childrens Hosp Philadelphia, Ctr Spatial & Funct Genom, Philadelphia, PA 19104 USA

[46] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[47] Childrens Hosp Philadelphia, Div Human Genet & Endocrinol & Diabet, Philadelphia, PA 19104 USA

[48] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA

[49] James J Peters VA Med Ctr, Psychiat Mental Illness Res Educ & Clin Ctr, Bronx, NY 10468 USA

[50] Icahn Sch Med Mt Sinai, Bronx, NY 10468 USA

来源：

SCIENCE | 2024年 / 385卷 / 6706期

关键词：

POSITIVE SELECTION; PROSTATE-CANCER; QUALITY-CONTROL; BIOBANK; DISEASE; HEALTH; RISK; PIGMENTATION; EXPRESSION; DESIGN;

D O I：

10.1126/science.adj1182

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

One of the justifiable criticisms of human genetic studies is the underrepresentation of participants from diverse populations. Lack of inclusion must be addressed at-scale to identify causal disease factors and understand the genetic causes of health disparities. We present genome-wide associations for 2068 traits from 635,969 participants in the Department of Veterans Affairs Million Veteran Program, a longitudinal study of diverse United States Veterans. Systematic analysis revealed 13,672 genomic risk loci; 1608 were only significant after including non-European populations. Fine-mapping identified causal variants at 6318 signals across 613 traits. One-third (n = 2069) were identified in participants from non-European populations. This reveals a broadly similar genetic architecture across populations, highlights genetic insights gained from underrepresented groups, and presents an extensive atlas of genetic associations.

引用

页数：12

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