Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program
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...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2024-07, Vol.385 (6706), p.eadj1182 |
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| creator | Verma, Anurag Huffman, Jennifer E Rodriguez, Alex Conery, Mitchell Liu, Molei Ho, Yuk-Lam Kim, Youngdae Heise, David A Guare, Lindsay Panickan, Vidul Ayakulangara Garcon, Helene Linares, Franciel Costa, Lauren Goethert, Ian Tipton, Ryan Honerlaw, Jacqueline Davies, Laura Whitbourne, Stacey Cohen, Jeremy Posner, Daniel C Sangar, Rahul Murray, Michael Wang, Xuan Dochtermann, Daniel R Devineni, Poornima Shi, Yunling Nandi, Tarak Nath Assimes, Themistocles L Brunette, Charles A Carroll, Robert J Clifford, Royce Duvall, Scott Gelernter, Joel Hung, Adriana Iyengar, Sudha K Joseph, Jacob Kember, Rachel Kranzler, Henry Kripke, Colleen M Levey, Daniel Luoh, Shiuh-Wen Merritt, Victoria C Overstreet, Cassie Deak, Joseph D Grant, Struan F A Polimanti, Renato Roussos, Panos Shakt, Gabrielle Sun, Yan V Tsao, Noah Venkatesh, Sanan Voloudakis, Georgios Justice, Amy Begoli, Edmon Ramoni, Rachel Tourassi, Georgia Pyarajan, Saiju Tsao, Philip O'Donnell, Christopher J Muralidhar, Sumitra Moser, Jennifer Casas, Juan P Bick, Alexander G Zhou, Wei Cai, Tianxi Voight, Benjamin F Cho, Kelly Gaziano, J Michael Madduri, Ravi K Damrauer, Scott Liao, Katherine P |
| description | 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 (
= 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. |
| doi_str_mv | 10.1126/science.adj1182 |
| format | Article |
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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 (
= 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.</description><subject>Alleles</subject><subject>Apolipoprotein E</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Datasets</subject><subject>Dementia disorders</subject><subject>Disproportionate Representation</subject><subject>Electronic health records</subject><subject>Electronic medical records</subject><subject>Ethnicity</subject><subject>Female</subject><subject>Frequency variation</subject><subject>Gene frequency</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomics</subject><subject>Genotypes</subject><subject>Heterogeneity</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Mapping</subject><subject>Phenotypes</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population (statistical)</subject><subject>Population genetics</subject><subject>Population studies</subject><subject>Quantitative Trait Loci</subject><subject>United States</subject><subject>United States Department of Veterans 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and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program</title><author>Verma, Anurag ; Huffman, Jennifer E ; Rodriguez, Alex ; Conery, Mitchell ; Liu, Molei ; Ho, Yuk-Lam ; Kim, Youngdae ; Heise, David A ; Guare, Lindsay ; Panickan, Vidul Ayakulangara ; Garcon, Helene ; Linares, Franciel ; Costa, Lauren ; Goethert, Ian ; Tipton, Ryan ; Honerlaw, Jacqueline ; Davies, Laura ; Whitbourne, Stacey ; Cohen, Jeremy ; Posner, Daniel C ; Sangar, Rahul ; Murray, Michael ; Wang, Xuan ; Dochtermann, Daniel R ; Devineni, Poornima ; Shi, Yunling ; Nandi, Tarak Nath ; Assimes, Themistocles L ; Brunette, Charles A ; Carroll, Robert J ; Clifford, Royce ; Duvall, Scott ; Gelernter, Joel ; Hung, Adriana ; Iyengar, Sudha K ; Joseph, Jacob ; Kember, Rachel ; Kranzler, Henry ; Kripke, Colleen M ; Levey, Daniel ; Luoh, Shiuh-Wen ; Merritt, Victoria C ; Overstreet, Cassie ; Deak, Joseph D ; Grant, Struan F A ; Polimanti, Renato ; Roussos, Panos ; Shakt, Gabrielle ; Sun, Yan V ; Tsao, Noah ; Venkatesh, Sanan ; Voloudakis, Georgios ; Justice, Amy ; Begoli, Edmon ; Ramoni, Rachel ; Tourassi, Georgia ; Pyarajan, Saiju ; Tsao, Philip ; O'Donnell, Christopher J ; Muralidhar, Sumitra ; Moser, Jennifer ; Casas, Juan P ; Bick, Alexander G ; Zhou, Wei ; Cai, Tianxi ; Voight, Benjamin F ; Cho, Kelly ; Gaziano, J Michael ; Madduri, Ravi K ; Damrauer, Scott ; Liao, Katherine P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c236t-4d7ffa08cf7cc6f7061d5fc2f86e38356b7df6c7ae0f15a176c494b20da140093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alleles</topic><topic>Apolipoprotein E</topic><topic>BASIC BIOLOGICAL SCIENCES</topic><topic>Datasets</topic><topic>Dementia disorders</topic><topic>Disproportionate Representation</topic><topic>Electronic health records</topic><topic>Electronic medical records</topic><topic>Ethnicity</topic><topic>Female</topic><topic>Frequency variation</topic><topic>Gene frequency</topic><topic>Gene mapping</topic><topic>Genes</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic Variation</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomics</topic><topic>Genotypes</topic><topic>Heterogeneity</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Mapping</topic><topic>Phenotypes</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population (statistical)</topic><topic>Population genetics</topic><topic>Population studies</topic><topic>Quantitative Trait Loci</topic><topic>United States</topic><topic>United States Department of Veterans Affairs</topic><topic>Veterans</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Verma, Anurag</creatorcontrib><creatorcontrib>Huffman, Jennifer E</creatorcontrib><creatorcontrib>Rodriguez, Alex</creatorcontrib><creatorcontrib>Conery, Mitchell</creatorcontrib><creatorcontrib>Liu, Molei</creatorcontrib><creatorcontrib>Ho, Yuk-Lam</creatorcontrib><creatorcontrib>Kim, Youngdae</creatorcontrib><creatorcontrib>Heise, David A</creatorcontrib><creatorcontrib>Guare, Lindsay</creatorcontrib><creatorcontrib>Panickan, Vidul Ayakulangara</creatorcontrib><creatorcontrib>Garcon, Helene</creatorcontrib><creatorcontrib>Linares, Franciel</creatorcontrib><creatorcontrib>Costa, Lauren</creatorcontrib><creatorcontrib>Goethert, Ian</creatorcontrib><creatorcontrib>Tipton, Ryan</creatorcontrib><creatorcontrib>Honerlaw, Jacqueline</creatorcontrib><creatorcontrib>Davies, Laura</creatorcontrib><creatorcontrib>Whitbourne, Stacey</creatorcontrib><creatorcontrib>Cohen, Jeremy</creatorcontrib><creatorcontrib>Posner, Daniel C</creatorcontrib><creatorcontrib>Sangar, Rahul</creatorcontrib><creatorcontrib>Murray, Michael</creatorcontrib><creatorcontrib>Wang, Xuan</creatorcontrib><creatorcontrib>Dochtermann, Daniel R</creatorcontrib><creatorcontrib>Devineni, Poornima</creatorcontrib><creatorcontrib>Shi, Yunling</creatorcontrib><creatorcontrib>Nandi, Tarak Nath</creatorcontrib><creatorcontrib>Assimes, Themistocles L</creatorcontrib><creatorcontrib>Brunette, Charles A</creatorcontrib><creatorcontrib>Carroll, Robert J</creatorcontrib><creatorcontrib>Clifford, Royce</creatorcontrib><creatorcontrib>Duvall, Scott</creatorcontrib><creatorcontrib>Gelernter, Joel</creatorcontrib><creatorcontrib>Hung, Adriana</creatorcontrib><creatorcontrib>Iyengar, Sudha K</creatorcontrib><creatorcontrib>Joseph, Jacob</creatorcontrib><creatorcontrib>Kember, Rachel</creatorcontrib><creatorcontrib>Kranzler, Henry</creatorcontrib><creatorcontrib>Kripke, Colleen M</creatorcontrib><creatorcontrib>Levey, Daniel</creatorcontrib><creatorcontrib>Luoh, Shiuh-Wen</creatorcontrib><creatorcontrib>Merritt, Victoria C</creatorcontrib><creatorcontrib>Overstreet, Cassie</creatorcontrib><creatorcontrib>Deak, Joseph D</creatorcontrib><creatorcontrib>Grant, Struan F A</creatorcontrib><creatorcontrib>Polimanti, Renato</creatorcontrib><creatorcontrib>Roussos, Panos</creatorcontrib><creatorcontrib>Shakt, Gabrielle</creatorcontrib><creatorcontrib>Sun, Yan V</creatorcontrib><creatorcontrib>Tsao, Noah</creatorcontrib><creatorcontrib>Venkatesh, Sanan</creatorcontrib><creatorcontrib>Voloudakis, Georgios</creatorcontrib><creatorcontrib>Justice, Amy</creatorcontrib><creatorcontrib>Begoli, Edmon</creatorcontrib><creatorcontrib>Ramoni, Rachel</creatorcontrib><creatorcontrib>Tourassi, Georgia</creatorcontrib><creatorcontrib>Pyarajan, Saiju</creatorcontrib><creatorcontrib>Tsao, Philip</creatorcontrib><creatorcontrib>O'Donnell, Christopher J</creatorcontrib><creatorcontrib>Muralidhar, Sumitra</creatorcontrib><creatorcontrib>Moser, Jennifer</creatorcontrib><creatorcontrib>Casas, Juan P</creatorcontrib><creatorcontrib>Bick, Alexander G</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Cai, Tianxi</creatorcontrib><creatorcontrib>Voight, Benjamin F</creatorcontrib><creatorcontrib>Cho, Kelly</creatorcontrib><creatorcontrib>Gaziano, J Michael</creatorcontrib><creatorcontrib>Madduri, Ravi K</creatorcontrib><creatorcontrib>Damrauer, Scott</creatorcontrib><creatorcontrib>Liao, Katherine P</creatorcontrib><creatorcontrib>Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology 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Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Verma, Anurag</au><au>Huffman, Jennifer E</au><au>Rodriguez, Alex</au><au>Conery, Mitchell</au><au>Liu, Molei</au><au>Ho, Yuk-Lam</au><au>Kim, Youngdae</au><au>Heise, David A</au><au>Guare, Lindsay</au><au>Panickan, Vidul Ayakulangara</au><au>Garcon, Helene</au><au>Linares, Franciel</au><au>Costa, Lauren</au><au>Goethert, Ian</au><au>Tipton, Ryan</au><au>Honerlaw, Jacqueline</au><au>Davies, Laura</au><au>Whitbourne, Stacey</au><au>Cohen, Jeremy</au><au>Posner, Daniel C</au><au>Sangar, Rahul</au><au>Murray, Michael</au><au>Wang, Xuan</au><au>Dochtermann, Daniel R</au><au>Devineni, Poornima</au><au>Shi, Yunling</au><au>Nandi, Tarak Nath</au><au>Assimes, Themistocles L</au><au>Brunette, Charles A</au><au>Carroll, Robert J</au><au>Clifford, Royce</au><au>Duvall, Scott</au><au>Gelernter, Joel</au><au>Hung, Adriana</au><au>Iyengar, Sudha K</au><au>Joseph, Jacob</au><au>Kember, Rachel</au><au>Kranzler, Henry</au><au>Kripke, Colleen M</au><au>Levey, Daniel</au><au>Luoh, Shiuh-Wen</au><au>Merritt, Victoria C</au><au>Overstreet, Cassie</au><au>Deak, Joseph D</au><au>Grant, Struan F A</au><au>Polimanti, Renato</au><au>Roussos, Panos</au><au>Shakt, Gabrielle</au><au>Sun, Yan V</au><au>Tsao, Noah</au><au>Venkatesh, Sanan</au><au>Voloudakis, Georgios</au><au>Justice, Amy</au><au>Begoli, Edmon</au><au>Ramoni, Rachel</au><au>Tourassi, Georgia</au><au>Pyarajan, Saiju</au><au>Tsao, Philip</au><au>O'Donnell, Christopher J</au><au>Muralidhar, Sumitra</au><au>Moser, Jennifer</au><au>Casas, Juan P</au><au>Bick, Alexander G</au><au>Zhou, Wei</au><au>Cai, Tianxi</au><au>Voight, Benjamin F</au><au>Cho, Kelly</au><au>Gaziano, J Michael</au><au>Madduri, Ravi K</au><au>Damrauer, Scott</au><au>Liao, Katherine P</au><aucorp>Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2024-07-19</date><risdate>2024</risdate><volume>385</volume><issue>6706</issue><spage>eadj1182</spage><pages>eadj1182-</pages><issn>0036-8075</issn><issn>1095-9203</issn><eissn>1095-9203</eissn><abstract>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 (
= 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.</abstract><cop>United States</cop><pub>The American Association for the Advancement of 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|
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2024-07, Vol.385 (6706), p.eadj1182 |
| issn | 0036-8075 1095-9203 1095-9203 |
| language | eng |
| recordid | cdi_osti_scitechconnect_2406806 |
| source | American Association for the Advancement of Science; MEDLINE |
| subjects | Alleles Apolipoprotein E BASIC BIOLOGICAL SCIENCES Datasets Dementia disorders Disproportionate Representation Electronic health records Electronic medical records Ethnicity Female Frequency variation Gene frequency Gene mapping Genes Genetic diversity Genetic Predisposition to Disease Genetic Variation Genome-wide association studies Genome-Wide Association Study Genomics Genotypes Heterogeneity Humans Longitudinal Studies Male Mapping Phenotypes Polymorphism, Single Nucleotide Population (statistical) Population genetics Population studies Quantitative Trait Loci United States United States Department of Veterans Affairs Veterans |
| title | Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T14%3A32%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Diversity%20and%20scale:%20Genetic%20architecture%20of%202068%20traits%20in%20the%20VA%20Million%20Veteran%20Program&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Verma,%20Anurag&rft.aucorp=Oak%20Ridge%20National%20Laboratory%20(ORNL),%20Oak%20Ridge,%20TN%20(United%20States)&rft.date=2024-07-19&rft.volume=385&rft.issue=6706&rft.spage=eadj1182&rft.pages=eadj1182-&rft.issn=0036-8075&rft.eissn=1095-9203&rft_id=info:doi/10.1126/science.adj1182&rft_dat=%3Cproquest_osti_%3E3082625671%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3082290624&rft_id=info:pmid/39024449&rfr_iscdi=true |