title: Common genetic variants and central adiposity among Asian-Indians.
abstract: Recent studies have identified common genetic variants that are unequivocally associated with central adiposity, BMI, and/or fasting plasma glucose among individuals of European descent. Our objective was to evaluate these associations in a population of Asian-Indians. We examined 16 single-nucleotide polymorphisms (SNPs) from loci previously linked to waist circumference, BMI, or fasting glucose in 1,129 Asian-Indians from New Delhi and Trivandrum. Trained medical staff measured waist circumference, height, and weight. Fasting plasma glucose was measured from collected blood specimens. Genotype-phenotype associations were evaluated using linear regression, with adjustments for age, gender, religion, and study region. For gene-environment interaction tests, total physical activity (PA) during the past 7 days was assessed by the International Physical Activity Questionnaire (IPAQ). The T allele at the FTO rs3751812 locus was associated with increased waist circumference (per allele effect of +1.58 cm, P(trend) = 0.0015) after Bonferroni adjustment for multiple testing (P(adj) = 0.04). We also found a nominally statistically significant FTO-PA interaction (P(interaction) = 0.008). Among participants with <81 metabolic equivalent (MET)-h/wk of PA, the rs3751812 variant was associated with increased waist size (+2.68 cm; 95% confidence interval (CI) = 1.24, 4.12), but not among those with 212+ MET-h/wk (-1.79 cm; 95% CI = -4.17, 0.58). No other variant had statistically significant associations, although statistical power was modest. In conclusion, we confirmed that an FTO variant associated with central adiposity in European populations is associated with central adiposity among Asian-Indians and corroborated prior reports indicating that high PA attenuates FTO-related genetic susceptibility to adiposity.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA. moorest@mail.nih.gov
authors.forename: Steven C
authors.initials: SC
authors.lastname: Moore
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Daniel
authors.forename: K Srinath
authors.initials: KS
authors.lastname: Reddy
authors.forename: Preeti S
authors.initials: PS
authors.lastname: George
authors.forename: Susan
authors.initials: S
authors.lastname: Yurgalevitch
authors.forename: Niveditha
authors.initials: N
authors.lastname: Devasenapathy
authors.forename: Lakshmy
authors.initials: L
authors.lastname: Ramakrishnan
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.forename: Aleyamma
authors.initials: A
authors.lastname: Mathew
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism; D015992:Body Mass Index; D004032:Diet / Q000706:statistics & numerical data*; D005215:Fasting / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D056128:Obesity, Abdominal / Q000235:genetics*; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D055105:Waist Circumference / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human