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dc.contributor.authorJustice, Anne E
dc.contributor.authorKaraderi, Tugce
dc.contributor.authorHighland, Heather M
dc.contributor.authorYoung, Kristin L
dc.contributor.authorGraff, Mariaelisa
dc.contributor.authorLu, Yingchang
dc.contributor.authorTurcot, Valerie
dc.contributor.authorAuer, Paul L
dc.contributor.authorFine, Rebecca S
dc.contributor.authorGuo, Xiuqing
dc.contributor.authorSchurmann, Claudia
dc.contributor.authorLempradl, Adelheid
dc.contributor.authorMarouli, Eirini
dc.contributor.authorCox, Amanda J
dc.contributor.authoret al.
dc.date.accessioned2019-09-27T03:24:26Z
dc.date.available2019-09-27T03:24:26Z
dc.date.issued2019
dc.identifier.issn1061-4036
dc.identifier.doi10.1038/s41588-018-0334-2
dc.identifier.urihttp://hdl.handle.net/10072/387849
dc.description.abstractBody-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom452
dc.relation.ispartofpageto469
dc.relation.ispartofissue3
dc.relation.ispartofjournalNature Genetics
dc.relation.ispartofvolume51
dc.subject.fieldofresearchBiological sciences
dc.subject.fieldofresearchBiomedical and clinical sciences
dc.subject.fieldofresearchcode31
dc.subject.fieldofresearchcode32
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsGenetics & Heredity
dc.subject.keywordsGENOME-WIDE ASSOCIATION
dc.subject.keywordsTYPE-2 DIABETES SUSCEPTIBILITY
dc.titleProtein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationJustice et al., Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution, Nature Genetics, 2019, 51 (3), pp. 452-469
dcterms.dateAccepted2018-12-17
dc.date.updated2019-09-27T03:09:38Z
gro.hasfulltextNo Full Text
gro.griffith.authorCox, Amanda J.


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