John Jeffrey Carr
Professor of Radiology, Biomedical Informatics and Cardiovascular Medicine
Last active: 9/11/2017

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

Fox CS, White CC, Lohman K, Heard-Costa N, Cohen P, Zhang Y, Johnson AD, Emilsson V, Liu CT, Chen YD, Taylor KD, Allison M, Budoff M, CARDIoGRAM Consortium, Rotter JI, Carr JJ, Hoffmann U, Ding J, Cupples LA, Liu Y
PLoS Genet. 2012 8 (5): e1002705

PMID: 22589742 · PMCID: PMC3349742 · DOI:10.1371/journal.pgen.1002705

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.

MeSH Terms (26)

Adipose Tissue Adult African Continental Ancestry Group Animals Asian Continental Ancestry Group Atherosclerosis Body Fat Distribution Body Mass Index Calcium-Calmodulin-Dependent Protein Kinases Coronary Disease European Continental Ancestry Group Female Gene Expression Regulation Genome-Wide Association Study Hispanic Americans Humans Intra-Abdominal Fat Intracellular Signaling Peptides and Proteins Male Mice Middle Aged Obesity Pericardium Polymorphism, Single Nucleotide Quantitative Trait Loci Tomography, X-Ray Computed

Connections (1)

This publication is referenced by other Labnodes entities:

Links