Show simple item record

dc.contributor.authorKraja, A.T.
dc.contributor.authorLiu, C.
dc.contributor.authorFetterman, J.L.
dc.date.accessioned2019-03-29T14:47:40Z
dc.date.available2019-03-29T14:47:40Z
dc.date.issued2019
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059497971&doi=10.1016%2fj.ajhg.2018.12.001&partnerID=40&md5=ed617b241e3a7c0db1549ab66fa8d182
dc.identifier.urihttp://hdl.handle.net/10713/8736
dc.description.abstractMitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia’s genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.en_US
dc.description.urihttps://dx.doi.org/10.1016/j.ajhg.2018.12.001en_US
dc.language.isoen_USen_US
dc.publisherCell Pressen_US
dc.relation.ispartofAmerican Journal of Human Genetics
dc.subjectBMIen_US
dc.subjectHbA1cen_US
dc.subjectHOMA-Ben_US
dc.subjectHOMA-IRen_US
dc.subjectMT-nDNA candidate genesen_US
dc.subjectmtDNAen_US
dc.subject.meshGlucoseen_US
dc.subject.meshInsulinen_US
dc.subject.meshMitochondriaen_US
dc.subject.meshWaist-Hip Ratio
dc.titleAssociations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traitsen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.ajhg.2018.12.001
dc.identifier.pmid30595373


Files in this item

Thumbnail
Name:
Publisher version

This item appears in the following Collection(s)

Show simple item record