Genetic variation near IRS1 is associated with adiposity and a favorable metabolic profile in U.S. Hispanics/Latinos.
Associations of IRS1 genetic variation with adiposity and metabolic profile in U.S. Hispanic/Latino individuals of diverse backgrounds were examined.



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.



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).



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.
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. qibin.qi@einstein.yu.edu.
Qibin
Q
Qi
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Stephanie M
0000-0002-7231-9745
SM
Gogarten
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Leslie S
LS
Emery
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Tin
T
Louie
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Adrienne
A
Stilp
Department of Biostatistics and Collaborative Studies Coordinating Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Jianwen
J
Cai
Department of Psychology, University of Miami, Miami, Florida, USA.
Neil
N
Schneiderman
Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
M Larissa
ML
Avilés-Santa
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Robert C
RC
Kaplan
Department of Epidemiology and Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina, USA.
Kari E
KE
North
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
Cathy C
CC
Laurie
Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
Ruth J F
RJ
Loos
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
Carmen R
CR
Isasi
D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000483:Alleles; D008076:Cholesterol, HDL / Q000097:blood; D005006:Ethnicity; D005215:Fasting / Q000097:blood; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006442:Glycated Hemoglobin / Q000032:analysis; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D014481:United States; D044465:White People / Q000235:genetics
D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D014280:Triglycerides; C526292:IRS1 protein, human
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