A phenome-wide association study
We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African...
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| Veröffentlicht in: | PloS one 2019-12, Vol.14 (12), p.e0226771 |
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| creator | Pendergrass, Sarah A Buyske, Steven Jeff, Janina M Frase, Alex Dudek, Scott Bradford, Yuki Ambite, Jose-Luis Avery, Christy L Buzkova, Petra Deelman, Ewa Fesinmeyer, Megan D Haiman, Christopher Heiss, Gerardo Hindorff, Lucia A Hsu, Chun-Nan Jackson, Rebecca D Lin, Yi Le Marchand, Loic Matise, Tara C Monroe, Kristine R Moreland, Larry North, Kari E Park, Sungshim L Reiner, Alex Wallace, Robert Wilkens, Lynne R Kooperberg, Charles Ritchie, Marylyn D Crawford, Dana C |
| description | We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p |
| doi_str_mv | 10.1371/journal.pone.0226771 |
| format | Article |
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The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0226771</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>African Americans ; Epidemiology ; Fibrosis ; Genetic aspects ; Genomes ; Genomics ; Glucose ; Hypertension ; Novels ; Phenotypes</subject><ispartof>PloS one, 2019-12, Vol.14 (12), p.e0226771</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids></links><search><creatorcontrib>Pendergrass, Sarah A</creatorcontrib><creatorcontrib>Buyske, Steven</creatorcontrib><creatorcontrib>Jeff, Janina M</creatorcontrib><creatorcontrib>Frase, Alex</creatorcontrib><creatorcontrib>Dudek, Scott</creatorcontrib><creatorcontrib>Bradford, Yuki</creatorcontrib><creatorcontrib>Ambite, Jose-Luis</creatorcontrib><creatorcontrib>Avery, Christy L</creatorcontrib><creatorcontrib>Buzkova, Petra</creatorcontrib><creatorcontrib>Deelman, Ewa</creatorcontrib><creatorcontrib>Fesinmeyer, Megan D</creatorcontrib><creatorcontrib>Haiman, Christopher</creatorcontrib><creatorcontrib>Heiss, Gerardo</creatorcontrib><creatorcontrib>Hindorff, Lucia A</creatorcontrib><creatorcontrib>Hsu, Chun-Nan</creatorcontrib><creatorcontrib>Jackson, Rebecca D</creatorcontrib><creatorcontrib>Lin, Yi</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Matise, Tara C</creatorcontrib><creatorcontrib>Monroe, Kristine R</creatorcontrib><creatorcontrib>Moreland, Larry</creatorcontrib><creatorcontrib>North, Kari E</creatorcontrib><creatorcontrib>Park, Sungshim L</creatorcontrib><creatorcontrib>Reiner, Alex</creatorcontrib><creatorcontrib>Wallace, Robert</creatorcontrib><creatorcontrib>Wilkens, Lynne R</creatorcontrib><creatorcontrib>Kooperberg, Charles</creatorcontrib><creatorcontrib>Ritchie, Marylyn D</creatorcontrib><creatorcontrib>Crawford, Dana C</creatorcontrib><title>A phenome-wide association study</title><title>PloS one</title><description>We performed a hypothesis-generating phenome-wide association study (PheWAS) to identify and characterize cross-phenotype associations, where one SNP is associated with two or more phenotypes, between thousands of genetic variants assayed on the Metabochip and hundreds of phenotypes in 5,897 African Americans as part of the Population Architecture using Genomics and Epidemiology (PAGE) I study. The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.</description><subject>African Americans</subject><subject>Epidemiology</subject><subject>Fibrosis</subject><subject>Genetic aspects</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Glucose</subject><subject>Hypertension</subject><subject>Novels</subject><subject>Phenotypes</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqFz0tLw0AUBeBBFKzVf-AiK8FF4jwyr2UoPgqFgha34WZy8yhxpjgJ6r9X0UVcubqHw8eBS8gloxkTmt3sw_TqYcgOwWNGOVdasyOyYFbwVHEqjmf5lJzFuKdUCqPUgiRFcujQhxdM3_oaE4gxuB7GPvgkjlP9cU5OGhgiXvzeJdnd3e5WD-lme79eFZu0tdakwJVtcmeMlA1amUtQNWphuWxsbazRUmlOuRDWOaDCmapCaeCrqqtcOi6W5PpntoUBy9674Ed8H1uYYizXT49loRhlyhpl_rHb57_2amY7hGHsYhim7wfjHH4CZPVeHA</recordid><startdate>20191231</startdate><enddate>20191231</enddate><creator>Pendergrass, Sarah A</creator><creator>Buyske, Steven</creator><creator>Jeff, Janina M</creator><creator>Frase, Alex</creator><creator>Dudek, Scott</creator><creator>Bradford, Yuki</creator><creator>Ambite, Jose-Luis</creator><creator>Avery, Christy L</creator><creator>Buzkova, Petra</creator><creator>Deelman, Ewa</creator><creator>Fesinmeyer, Megan D</creator><creator>Haiman, Christopher</creator><creator>Heiss, Gerardo</creator><creator>Hindorff, Lucia A</creator><creator>Hsu, Chun-Nan</creator><creator>Jackson, Rebecca D</creator><creator>Lin, Yi</creator><creator>Le Marchand, Loic</creator><creator>Matise, Tara C</creator><creator>Monroe, Kristine R</creator><creator>Moreland, Larry</creator><creator>North, Kari E</creator><creator>Park, Sungshim L</creator><creator>Reiner, Alex</creator><creator>Wallace, Robert</creator><creator>Wilkens, Lynne R</creator><creator>Kooperberg, Charles</creator><creator>Ritchie, Marylyn D</creator><creator>Crawford, Dana C</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20191231</creationdate><title>A phenome-wide association study</title><author>Pendergrass, Sarah A ; 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The PAGE I study was a National Human Genome Research Institute-funded collaboration of four study sites accessing diverse epidemiologic studies genotyped on the Metabochip, a custom genotyping chip that has dense coverage of regions in the genome previously associated with cardio-metabolic traits and outcomes in mostly European-descent populations. Here we focus on identifying novel phenome-genome relationships, where SNPs are associated with more than one phenotype. To do this, we performed a PheWAS, testing each SNP on the Metabochip for an association with up to 273 phenotypes in the participating PAGE I study sites. We identified 133 putative pleiotropic variants, defined as SNPs associated at an empirically derived p-value threshold of p<0.01 in two or more PAGE study sites for two or more phenotype classes. We further annotated these PheWAS-identified variants using publicly available functional data and local genetic ancestry. Amongst our novel findings is SPARC rs4958487, associated with increased glucose levels and hypertension. SPARC has been implicated in the pathogenesis of diabetes and is also known to have a potential role in fibrosis, a common consequence of multiple conditions including hypertension. The SPARC example and others highlight the potential that PheWAS approaches have in improving our understanding of complex disease architecture by identifying novel relationships between genetic variants and an array of common human phenotypes.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0226771</doi><tpages>e0226771</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | PloS one, 2019-12, Vol.14 (12), p.e0226771 |
| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | African Americans Epidemiology Fibrosis Genetic aspects Genomes Genomics Glucose Hypertension Novels Phenotypes |
| title | A phenome-wide association study |
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