Show simple item record

dc.contributor.authorByars, SG
dc.contributor.authorHuang, QQ
dc.contributor.authorGray, L-A
dc.contributor.authorBakshi, A
dc.contributor.authorRipatti, S
dc.contributor.authorAbraham, G
dc.contributor.authorStearns, SC
dc.contributor.authorInouye, M
dc.date.accessioned2021-02-04T02:07:47Z
dc.date.available2021-02-04T02:07:47Z
dc.date.issued2017-06-01
dc.identifierpii: PGENETICS-D-16-01943
dc.identifier.citationByars, S. G., Huang, Q. Q., Gray, L. -A., Bakshi, A., Ripatti, S., Abraham, G., Stearns, S. C. & Inouye, M. (2017). Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy. PLOS GENETICS, 13 (6), https://doi.org/10.1371/journal.pgen.1006328.
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/11343/259582
dc.description.abstractTraditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGenetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pgen.1006328
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentSchool of BioSciences
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.affiliation.facultyScience
melbourne.source.titlePLoS Genetics
melbourne.source.volume13
melbourne.source.issue6
melbourne.identifier.nhmrc1062227
melbourne.identifier.nhmrc1061435
melbourne.identifier.nhmrc1090462
dc.rights.licenseCC BY
melbourne.elementsid1216877
melbourne.contributor.authorByars, Sean
melbourne.contributor.authorBakshi, Andrew
melbourne.contributor.authorAbraham, Gad
melbourne.contributor.authorInouye, Michael
dc.identifier.eissn1553-7404
melbourne.identifier.fundernameidNHMRC, 1062227
melbourne.identifier.fundernameidNHMRC, 1061435
melbourne.identifier.fundernameidNHMRC, 1090462
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record