title: Genome-wide association of pericardial fat identifies a unique locus for ectopic fat.
abstract: 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.
authors.affiliation: Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, United States of America. foxca@nhlbi.nih.gov
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Charles C
authors.initials: CC
authors.lastname: White
authors.forename: Kurt
authors.initials: K
authors.lastname: Lohman
authors.forename: Nancy
authors.initials: N
authors.lastname: Heard-Costa
authors.forename: Paul
authors.initials: P
authors.lastname: Cohen
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Johnson
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.forename: Y-D Ida
authors.initials: YD
authors.lastname: Chen
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Matthew
authors.initials: M
authors.lastname: Allison
authors.forename: Matthew
authors.initials: M
authors.lastname: Budoff
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Ding
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D000818:Animals; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics; D044383:Black People / Q000235:genetics; D050218:Body Fat Distribution; D015992:Body Mass Index; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003327:Coronary Disease / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010496:Pericardium / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D014057:Tomography, X-Ray Computed; D044465:White People / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human