Qibin Qi1, Stephanie M Gogarten2, Leslie S Emery2, Tin Louie2, Adrienne Stilp2, Jianwen Cai3, Neil Schneiderman4, M Larissa Avilés-Santa5, Robert C Kaplan6, Kari E North7, Cathy C Laurie2, Ruth J F Loos8, Carmen R Isasi6. 1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. qibin.qi@einstein.yu.edu. 2. Department of Biostatistics, University of Washington, Seattle, Washington, USA. 3. Department of Biostatistics and Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina, USA. 4. Department of Psychology, University of Miami, Miami, Florida, USA. 5. Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. 6. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. 7. Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina, USA. 8. Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Abstract
OBJECTIVE: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. 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 (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. RESULTS: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% 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, it was 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). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). CONCLUSIONS: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women.
OBJECTIVE: Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined. 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 (5,232 men; 7,515 women) from the Hispanic Community Health Study/Study of Latinos. RESULTS: The C-allele (frequency = 26%) of rs2943650 was significantly associated with higher BF% 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, it was 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). The BF%-increasing allele of rs2943650 was significantly associated with lower levels of fasting insulin, homeostatic model assessment of insulin resistance, hemoglobin A1c, and triglycerides and higher high-density lipoprotein cholesterol (P < 0.05). CONCLUSIONS: This study confirmed and extended previous findings of IRS1 variation associated with increased adiposity but a favorable metabolic profile in U.S. Hispanics/Latinos, with a relatively stronger genetic effect on BF% in Hispanic/Latino women compared with European women.
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