Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos.

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.

• Authors: Qibin Qi, Stephanie M Gogarten, Leslie S Emery, Tin Louie, Adrienne Stilp, Jianwen Cai, Neil Schneiderman, M Larissa Avilés-Santa, Robert C Kaplan, Kari E North, Cathy C Laurie, Ruth J F Loos, Carmen R Isasi
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 24 Issue 11 Pg. 2407-2413 (11 2016) ISSN: 1930-739X [Electronic] United States
• PMID: 27663718 (Publication Type: Journal Article)
• Copyright: © 2016 The Obesity Society.

Chemical References

• Cholesterol, HDL
• Glycated Hemoglobin A
• IRS1 protein, human
• Insulin
• Insulin Receptor Substrate Proteins
• Triglycerides

Topics

• Adiposity (genetics)
• Adult
• Alleles
• Cholesterol, HDL (blood)
• Ethnicity
• Fasting (blood)
• Female
• Gene Frequency
• Genetic Variation
• Genome-Wide Association Study
• Glycated Hemoglobin (analysis)
• Hispanic or Latino (genetics)
• Humans
• Insulin (blood)
• Insulin Receptor Substrate Proteins (genetics)
• Insulin Resistance (genetics)
• Male
• Metabolome
• Middle Aged
• Obesity (genetics)
• Risk Factors
• Sex Factors
• Triglycerides (blood)
• United States
• White People (genetics)