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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, ethnic groups, European Continental Ancestry Group, Fasting, Female, Gene Frequency, Genetic Variation, genome-wide association study, Glycated Hemoglobin A, Hispanic Americans, Humans, insulin, Insulin Receptor Substrate Proteins, insulin resistance, Male, Metabolome, Middle Aged, Obesity, Risk Factors, Sex Factors, triglycerides, United States
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