Abstract 2071: Genome-wide Association Study Identifies Genes Linking Abdominal Fat, Inflammation and Other Cardiovascular Disease Risk Factors in the Quebec Family Study
Background: Inflammation is a common feature of abdominal obesity, type-2 diabetes and cardiovascular disease (CVD). Since adipose tissue secretes large amounts of atheroinflammatory molecules, we hypothesized that genes influencing abdominal fat level could also influence cardiometabolic risk factors.
Methods: We performed a genome-wide association study (GWAS) of abdominal fat, adipocytokines and CVD risk factors in 929 subjects from the Quebec Family Study using the Human Illumina 610-Quad chip. Abdominal fat phenotypes included waist circumference (WC), visceral (VAT), subcutaneous (SAT) and total (TAT) abdominal adipose tissue areas measured by computed tomography. Circulating levels of C-reactive protein (CRP), adiponectin (ADIPO), interleukin-6 (IL6) and tumor necrosis factor-alpha (TNFα) and several CVD risk factors including blood pressure (BP), blood lipids and fasting levels of glucose (GLU) and insulin (INS) were also measured. A total of 543,714 autosomal SNPs were tested for association using the measured genotype approach implemented in SOLAR that takes into account the non-independence among family members.
Results: In the primary analyses, the best hits (SNPs with the lowest p-values) for each of the age-sex- and BMI-adjusted abdominal fat phenotypes were found in/near three genes located on chromosomes 6q25 for WC (p =3.1 ×10−7), 16q24 for SAT (p =1.6 ×10−7) and 4q31 for VAT (2.6 × 10−6), respectively. Several SNPs in each of these genes were also found to be pleiotropically associated (p <0.001) with many CVD risk factors. SNPs in the gene associated with SAT were also associated with CRP, ADIPO, IL6, TNFα, BP, blood lipids, GLU and INS. Similarly, SNPs in the gene associated with VAT were also associated with CRP, ADIPO, TNFα, BP, HDL-cholesterol, GLU and INS, while SNPs in the gene associated with WC were also associated with CRP, ADIPO, IL6, BP, triglycerides and GLU.
Conclusion: Although some of the associations reported here do not reach the formal threshold of genome-wide significance (5.0 × 10−7), they suggest the presence of molecular links between abdominal obesity, inflammation and cardiometabolic risk factors. Replication studies of the associations reported herein are warranted.