Abstract:
:Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery rate. Among an approximately 680 known genome-wide association study (GWAS) loci for cardio-metabolic traits, we identified 140 coincident cis-eQTLs at 109 GWAS loci, including 93 eQTLs not previously described. At 49 of these 140 eQTLs, gene expression was nominally associated (p < 0.05) with levels of the GWAS trait. The size of our dataset enabled identification of five loci associated (p < 5 × 10-8) with at least five genes located >5 Mb away. These trans-eQTL signals confirmed and extended the previously reported KLF14-mediated network to 55 target genes, validated the CIITA regulation of class II MHC genes, and identified ZNF800 as a candidate master regulator. Finally, we observed similar expression-clinical trait correlations of genes associated with GWAS loci in both humans and a panel of genetically diverse mice. These results provide candidate genes for further investigation of their potential roles in adipose biology and in regulating cardio-metabolic traits.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Civelek M,Wu Y,Pan C,Raulerson CK,Ko A,He A,Tilford C,Saleem NK,Stančáková A,Scott LJ,Fuchsberger C,Stringham HM,Jackson AU,Narisu N,Chines PS,Small KS,Kuusisto J,Parks BW,Pajukanta P,Kirchgessner T,Collins FS,Gdoi
10.1016/j.ajhg.2017.01.027subject
Has Abstractpub_date
2017-03-02 00:00:00pages
428-443issue
3eissn
0002-9297issn
1537-6605pii
S0002-9297(17)30028-9journal_volume
100pub_type
杂志文章abstract::With the imminent availability of ultra-high-volume genotyping platforms (on the order of 100,000-1,000,000 genotypes per sample) at a manageable cost, there is growing interest in the possibility of conducting genomewide association studies for a variety of diseases but, so far, little consensus on methods to design ...
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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