Objective
We examined associations of IRS1 genetic variation with adiposity and metabolic profile in US Hispanic/Latino individuals of diverse backgrounds.
Methods
Previously genome-wide association study identified IRS1 variants (rs2943650, rs2972146, rs2943641, and rs2943634) as related to body fat percentage (BF%) and multiple metabolic traits were tested among up to 12,730 adults (5232 men; 7515 women) from the Hispanic Community Health Study/Study of Latinos.
Results
The C-allele (frequency=26%) of rs2943650 was significantly associated with higher BF% in overall (β=0.34±0.11% per allele; P=0.002) and in women (β=0.41±0.14% per C-allele; P=0.003), but not in men (β=0.28±0.18% per C-allele; P=0.11), though there was no significant sex-difference. Using the inverse-normal-transformed data to compare effect sizes, we found that the association with BF% was stronger in Hispanic/Latino women than that previously reported in European women (β=0.054±0.018SD vs β=0.008±0.011SD per C-allele; P=0.03). We also observed that the BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, HOMA-IR, Hemoglobin A1c and triglycerides, and higher HDL-cholesterol (P<0.05).
Conclusions
Our study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in US Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared to European women.