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dc.contributor.authorNatarajan, P.
dc.contributor.authorPeloso, G.M.
dc.contributor.authorZekavat, S.M.
dc.date.accessioned2019-06-21T18:46:35Z
dc.date.available2019-06-21T18:46:35Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85052245414&doi=10.1038%2fs41467-018-05747-8&partnerID=40&md5=681d90285a75346c98d0bd2fc236e3aa
dc.identifier.urihttp://hdl.handle.net/10713/9805
dc.description.abstractLarge-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth >29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia. Copyright 2018, The Author(s).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41467-018-05747-8en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature Communications
dc.subjectBase Sequenceen_US
dc.subjectCholesterol, LDLen_US
dc.subjectGene Frequencyen_US
dc.subjectGenome, Humanen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHigh-Throughput Nucleotide Sequencingen_US
dc.subjectHumansen_US
dc.subjectLipidsen_US
dc.subjectModels, Geneticen_US
dc.subjectMutationen_US
dc.titleDeep-coverage whole genome sequences and blood lipids among 16,324 individualsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-018-05747-8
dc.identifier.pmid30140000


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