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Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.

Publication ,  Journal Article
Fox, CS; White, CC; Lohman, K; Heard-Costa, N; Cohen, P; Zhang, Y; Johnson, AD; Emilsson, V; Liu, C-T; Chen, Y-DI; Taylor, KD; Allison, M ...
Published in: PLoS Genet
2012

Pericardial fat is a localized fat depot associated with coronary artery calcium and myocardial infarction. We hypothesized that genetic loci would be associated with pericardial fat independent of other body fat depots. Pericardial fat was quantified in 5,487 individuals of European ancestry from the Framingham Heart Study (FHS) and the Multi-Ethnic Study of Atherosclerosis (MESA). Genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of pericardial fat adjusted for age, sex, weight, and height. A weighted z-score meta-analysis was conducted, and validation was obtained in an additional 3,602 multi-ethnic individuals from the MESA study. We identified a genome-wide significant signal in our primary meta-analysis at rs10198628 near TRIB2 (MAF 0.49, p = 2.7 × 10(-08)). This SNP was not associated with visceral fat (p = 0.17) or body mass index (p = 0.38), although we observed direction-consistent, nominal significance with visceral fat adjusted for BMI (p = 0.01) in the Framingham Heart Study. Our findings were robust among African ancestry (n = 1,442, p = 0.001), Hispanic (n = 1,399, p = 0.004), and Chinese (n = 761, p = 0.007) participants from the MESA study, with a combined p-value of 5.4E-14. We observed TRIB2 gene expression in the pericardial fat of mice. rs10198628 near TRIB2 is associated with pericardial fat but not measures of generalized or visceral adiposity, reinforcing the concept that there are unique genetic underpinnings to ectopic fat distribution.

Duke Scholars

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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

2012

Volume

8

Issue

5

Start / End Page

e1002705

Location

United States

Related Subject Headings

  • White People
  • Tomography, X-Ray Computed
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Pericardium
  • Obesity
  • Middle Aged
  • Mice
  • Male
  • Intracellular Signaling Peptides and Proteins
 

Citation

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Fox, C. S., White, C. C., Lohman, K., Heard-Costa, N., Cohen, P., Zhang, Y., … Liu, Y. (2012). Genome-wide association of pericardial fat identifies a unique locus for ectopic fat. PLoS Genet, 8(5), e1002705. https://doi.org/10.1371/journal.pgen.1002705
Fox, Caroline S., Charles C. White, Kurt Lohman, Nancy Heard-Costa, Paul Cohen, Yingying Zhang, Andrew D. Johnson, et al. “Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.PLoS Genet 8, no. 5 (2012): e1002705. https://doi.org/10.1371/journal.pgen.1002705.
Fox CS, White CC, Lohman K, Heard-Costa N, Cohen P, Zhang Y, et al. Genome-wide association of pericardial fat identifies a unique locus for ectopic fat. PLoS Genet. 2012;8(5):e1002705.
Fox, Caroline S., et al. “Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.PLoS Genet, vol. 8, no. 5, 2012, p. e1002705. Pubmed, doi:10.1371/journal.pgen.1002705.
Fox CS, White CC, Lohman K, Heard-Costa N, Cohen P, Zhang Y, Johnson AD, Emilsson V, Liu C-T, Chen Y-DI, Taylor KD, Allison M, Budoff M, CARDIoGRAM Consortium, Rotter JI, Carr JJ, Hoffmann U, Ding J, Cupples LA, Liu Y. Genome-wide association of pericardial fat identifies a unique locus for ectopic fat. PLoS Genet. 2012;8(5):e1002705.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

2012

Volume

8

Issue

5

Start / End Page

e1002705

Location

United States

Related Subject Headings

  • White People
  • Tomography, X-Ray Computed
  • Quantitative Trait Loci
  • Polymorphism, Single Nucleotide
  • Pericardium
  • Obesity
  • Middle Aged
  • Mice
  • Male
  • Intracellular Signaling Peptides and Proteins