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

TitleGenetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos.
Publication TypePublication
Year2016
AuthorsQi Q, Gogarten SM, Emery LS, Louie T, Stilp A, Cai J, Schneiderman N, M Avilés-Santa L, Kaplan RC, North KE, Laurie CC, Loos RJF, Isasi CR
JournalObesity (Silver Spring)
Volume24
Issue11
Pagination2407-2413
Date Published2016 11
ISSN1930-739X
Keywordsadiposity, Adult, Alleles, Cholesterol, HDL, ethnicity, Fasting, Female, Gene Frequency, Genetic Variation, genome-wide association study, Glycated Hemoglobin A, Hispanic or Latino, Humans, insulin, Insulin Receptor Substrate Proteins, insulin resistance, Male, Metabolome, Middle Aged, Obesity, Risk Factors, Sex Factors, triglycerides, United States, Whites
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.

DOI10.1002/oby.21624
Alternate JournalObesity (Silver Spring)
PubMed ID27663718
PubMed Central IDPMC5093062
Grant ListHHSN268201300005C / HL / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
K01 HL129892 / HL / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
U54 TR000123 / TR / NCATS NIH HHS / United States
UL1 TR001073 / TR / NCATS NIH HHS / United States
P30 DK020541 / DK / NIDDK NIH HHS / United States
MS#: 
0359
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Yes
Manuscript Status: 
Published