Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study
Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi...
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| Veröffentlicht in: | Journal of human genetics 2018-03, Vol.63 (3), p.327-337 |
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| creator | Raffield, Laura M Ellis, Jaclyn Olson, Nels C Duan, Qing Li, Jin Durda, Peter Pankratz, Nathan Keating, Brendan J Wassel, Christina L Cushman, Mary Wilson, James G Gross, Myron D Tracy, Russell P Rich, Stephen S Reiner, Alex P Li, Yun Willis, Monte S Lange, Ethan M Lange, Leslie A |
| description | Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p |
| doi_str_mv | 10.1038/s10038-017-0384-9 |
| format | Article |
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) for the NOX4 locus (lead variant rs2289125, β = -0.15, p = 5.3 × 10
). While the NOX4 locus was previously reported as associated with Hcy in European-American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.</description><identifier>ISSN: 1434-5161</identifier><identifier>ISSN: 1435-232X</identifier><identifier>EISSN: 1435-232X</identifier><identifier>DOI: 10.1038/s10038-017-0384-9</identifier><identifier>PMID: 29321517</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adult ; Alleles ; Arteriosclerosis ; Atherosclerosis ; Atherosclerosis - blood ; Atherosclerosis - epidemiology ; Atherosclerosis - genetics ; Black or African American - genetics ; Coronary artery ; Coronary Artery Disease - blood ; Coronary Artery Disease - epidemiology ; Coronary Artery Disease - genetics ; Coronary vessels ; Dementia disorders ; Female ; Females ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotype ; Homocysteine ; Homocysteine - blood ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Mississippi - epidemiology ; NOX4 protein ; Polymorphism, Single Nucleotide ; Population genetics ; Population Surveillance ; Quantitative Trait Loci ; Quantitative Trait, Heritable ; Sex ; Vascular diseases ; Young Adult ; Young adults</subject><ispartof>Journal of human genetics, 2018-03, Vol.63 (3), p.327-337</ispartof><rights>Copyright Nature Publishing Group Mar 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-dcf3dfcfc53ea391da458b726a6342127e2bd8e1dcebac950e3710b0aec1d053</citedby><cites>FETCH-LOGICAL-c517t-dcf3dfcfc53ea391da458b726a6342127e2bd8e1dcebac950e3710b0aec1d053</cites><orcidid>0000-0002-0769-5816</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29321517$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raffield, Laura M</creatorcontrib><creatorcontrib>Ellis, Jaclyn</creatorcontrib><creatorcontrib>Olson, Nels C</creatorcontrib><creatorcontrib>Duan, Qing</creatorcontrib><creatorcontrib>Li, Jin</creatorcontrib><creatorcontrib>Durda, Peter</creatorcontrib><creatorcontrib>Pankratz, Nathan</creatorcontrib><creatorcontrib>Keating, Brendan J</creatorcontrib><creatorcontrib>Wassel, Christina L</creatorcontrib><creatorcontrib>Cushman, Mary</creatorcontrib><creatorcontrib>Wilson, James G</creatorcontrib><creatorcontrib>Gross, Myron D</creatorcontrib><creatorcontrib>Tracy, Russell P</creatorcontrib><creatorcontrib>Rich, Stephen S</creatorcontrib><creatorcontrib>Reiner, Alex P</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Willis, Monte S</creatorcontrib><creatorcontrib>Lange, Ethan M</creatorcontrib><creatorcontrib>Lange, Leslie A</creatorcontrib><title>Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study</title><title>Journal of human genetics</title><addtitle>J Hum Genet</addtitle><description>Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p < 5.0 × 10
) for the NOX4 locus (lead variant rs2289125, β = -0.15, p = 5.3 × 10
). While the NOX4 locus was previously reported as associated with Hcy in European-American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.</description><subject>Adult</subject><subject>Alleles</subject><subject>Arteriosclerosis</subject><subject>Atherosclerosis</subject><subject>Atherosclerosis - blood</subject><subject>Atherosclerosis - epidemiology</subject><subject>Atherosclerosis - genetics</subject><subject>Black or African American - genetics</subject><subject>Coronary artery</subject><subject>Coronary Artery Disease - blood</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Coronary vessels</subject><subject>Dementia disorders</subject><subject>Female</subject><subject>Females</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Homocysteine</subject><subject>Homocysteine - blood</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mississippi - epidemiology</subject><subject>NOX4 protein</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population genetics</subject><subject>Population Surveillance</subject><subject>Quantitative Trait Loci</subject><subject>Quantitative Trait, Heritable</subject><subject>Sex</subject><subject>Vascular diseases</subject><subject>Young Adult</subject><subject>Young adults</subject><issn>1434-5161</issn><issn>1435-232X</issn><issn>1435-232X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdUstu1DAUjRCIPuAD2CBLbFjU4Ec8TjZI0agPUBESdAEry2PfdNwmdrEd0Pwc34YzKRWw8bnyPff4XOtU1QtK3lDCm7eJkgKYUIkL1rh9VB3SmgvMOPv6eF_XWNAVPaiOUrohhc0ke1odsJYzKqg8rH6dgw8j4J_OAtIpBeN0dsGjlCe7Q6FH2zAGs0sZnAfkPOr66IwuOMK-SKiPYUR5C-iDNrepzF6Ajhl9mRVO9o2P05AdPs1b78xyPyt3pRVDMsN8unSCtLd7-jrE4HXcoS5mKPDZpdv56W9h8teos0UtLQafVU96PSR4fo_H1dXZ6dX6Al9-On-_7i6xKVtmbE3PbW96Izho3lKra9FsJFvpFa8ZZRLYxjZArYGNNq0gwCUlG6LBUEsEP67eLbJ302aEwvI56kHdRTcWmypop_7teLdV1-GHEg1bNbwtAq_vBWL4PkHKanTJwDBoD2FKirZNK6QUDS3UV_9Rb8IUfdlOMUJkK2vGZkG6sEz5uxShfzBDiZrDoZZwqBIONYdDzTMv_97iYeJPGvhv5Ka6cQ</recordid><startdate>20180301</startdate><enddate>20180301</enddate><creator>Raffield, Laura M</creator><creator>Ellis, Jaclyn</creator><creator>Olson, Nels C</creator><creator>Duan, Qing</creator><creator>Li, Jin</creator><creator>Durda, Peter</creator><creator>Pankratz, Nathan</creator><creator>Keating, Brendan J</creator><creator>Wassel, Christina L</creator><creator>Cushman, Mary</creator><creator>Wilson, James G</creator><creator>Gross, Myron D</creator><creator>Tracy, Russell P</creator><creator>Rich, Stephen S</creator><creator>Reiner, Alex P</creator><creator>Li, Yun</creator><creator>Willis, Monte S</creator><creator>Lange, Ethan M</creator><creator>Lange, Leslie A</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0769-5816</orcidid></search><sort><creationdate>20180301</creationdate><title>Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study</title><author>Raffield, Laura M ; Ellis, Jaclyn ; Olson, Nels C ; Duan, Qing ; Li, Jin ; Durda, Peter ; Pankratz, Nathan ; Keating, Brendan J ; Wassel, Christina L ; Cushman, Mary ; Wilson, James G ; Gross, Myron D ; Tracy, Russell P ; Rich, Stephen S ; Reiner, Alex P ; Li, Yun ; Willis, Monte S ; Lange, Ethan M ; Lange, Leslie A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-dcf3dfcfc53ea391da458b726a6342127e2bd8e1dcebac950e3710b0aec1d053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Arteriosclerosis</topic><topic>Atherosclerosis</topic><topic>Atherosclerosis - blood</topic><topic>Atherosclerosis - epidemiology</topic><topic>Atherosclerosis - genetics</topic><topic>Black or African American - genetics</topic><topic>Coronary artery</topic><topic>Coronary Artery Disease - blood</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Coronary Artery Disease - genetics</topic><topic>Coronary vessels</topic><topic>Dementia disorders</topic><topic>Female</topic><topic>Females</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype</topic><topic>Homocysteine</topic><topic>Homocysteine - blood</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mississippi - epidemiology</topic><topic>NOX4 protein</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population genetics</topic><topic>Population Surveillance</topic><topic>Quantitative Trait Loci</topic><topic>Quantitative Trait, Heritable</topic><topic>Sex</topic><topic>Vascular diseases</topic><topic>Young Adult</topic><topic>Young adults</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raffield, Laura M</creatorcontrib><creatorcontrib>Ellis, Jaclyn</creatorcontrib><creatorcontrib>Olson, Nels C</creatorcontrib><creatorcontrib>Duan, Qing</creatorcontrib><creatorcontrib>Li, Jin</creatorcontrib><creatorcontrib>Durda, Peter</creatorcontrib><creatorcontrib>Pankratz, Nathan</creatorcontrib><creatorcontrib>Keating, Brendan J</creatorcontrib><creatorcontrib>Wassel, Christina L</creatorcontrib><creatorcontrib>Cushman, Mary</creatorcontrib><creatorcontrib>Wilson, James G</creatorcontrib><creatorcontrib>Gross, Myron D</creatorcontrib><creatorcontrib>Tracy, Russell P</creatorcontrib><creatorcontrib>Rich, Stephen S</creatorcontrib><creatorcontrib>Reiner, Alex P</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Willis, Monte S</creatorcontrib><creatorcontrib>Lange, Ethan M</creatorcontrib><creatorcontrib>Lange, Leslie A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raffield, Laura M</au><au>Ellis, Jaclyn</au><au>Olson, Nels C</au><au>Duan, Qing</au><au>Li, Jin</au><au>Durda, Peter</au><au>Pankratz, Nathan</au><au>Keating, Brendan J</au><au>Wassel, Christina L</au><au>Cushman, Mary</au><au>Wilson, James G</au><au>Gross, Myron D</au><au>Tracy, Russell P</au><au>Rich, Stephen S</au><au>Reiner, Alex P</au><au>Li, Yun</au><au>Willis, Monte S</au><au>Lange, Ethan M</au><au>Lange, Leslie A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study</atitle><jtitle>Journal of human genetics</jtitle><addtitle>J Hum Genet</addtitle><date>2018-03-01</date><risdate>2018</risdate><volume>63</volume><issue>3</issue><spage>327</spage><epage>337</epage><pages>327-337</pages><issn>1434-5161</issn><issn>1435-232X</issn><eissn>1435-232X</eissn><abstract>Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease, stroke, and dementia. Little is known about genetic associations with Hcy in individuals of African ancestry. We performed a genome-wide association study for Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA) study. Analyses were stratified by sex and results were meta-analyzed within and across sex. In the sex-combined meta-analysis, we observed genome-wide significant evidence (p < 5.0 × 10
) for the NOX4 locus (lead variant rs2289125, β = -0.15, p = 5.3 × 10
). While the NOX4 locus was previously reported as associated with Hcy in European-American populations, rs2289125 remained genome-wide significant when conditioned on the previously reported lead variants. Previously reported genome-wide significant associations at NOX4, MTR, CBS, and MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the CPS1 locus, previously reported in females only, also was replicated specifically in females in this analysis, supporting sex-specific effects for this locus. These results suggest that there may be a combination of cross-population and population-specific genetic effects, as well as differences in genetic effects between males and females, in the regulation of Hcy levels.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>29321517</pmid><doi>10.1038/s10038-017-0384-9</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-0769-5816</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Alleles Arteriosclerosis Atherosclerosis Atherosclerosis - blood Atherosclerosis - epidemiology Atherosclerosis - genetics Black or African American - genetics Coronary artery Coronary Artery Disease - blood Coronary Artery Disease - epidemiology Coronary Artery Disease - genetics Coronary vessels Dementia disorders Female Females Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Genomes Genotype Homocysteine Homocysteine - blood Humans Longitudinal Studies Male Middle Aged Mississippi - epidemiology NOX4 protein Polymorphism, Single Nucleotide Population genetics Population Surveillance Quantitative Trait Loci Quantitative Trait, Heritable Sex Vascular diseases Young Adult Young adults |
| title | Genome-wide association study of homocysteine in African Americans from the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary Artery Risk in Young Adults study |
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