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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.issn1061-4036en_US
dc.identifier.doi10.1038/s41588-018-0334-2en_US
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.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofpagefrom452en_US
dc.relation.ispartofpageto469en_US
dc.relation.ispartofissue3en_US
dc.relation.ispartofjournalNature Geneticsen_US
dc.relation.ispartofvolume51en_US
dc.subject.fieldofresearchMedical and Health Sciencesen_US
dc.subject.fieldofresearchBiological Sciencesen_US
dc.subject.fieldofresearchcode11en_US
dc.subject.fieldofresearchcode06en_US
dc.subject.keywordsScience & Technologyen_US
dc.subject.keywordsLife Sciences & Biomedicineen_US
dc.subject.keywordsGenetics & Heredityen_US
dc.subject.keywordsGENOME-WIDE ASSOCIATIONen_US
dc.subject.keywordsTYPE-2 DIABETES SUSCEPTIBILITYen_US
dc.titleProtein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distributionen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
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. 452-469en_US
dcterms.dateAccepted2018-12-17
dc.date.updated2019-09-27T03:09:38Z
gro.hasfulltextNo Full Text
gro.griffith.authorCox, Amanda J.


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