title: Joint association of nicotinic acetylcholine receptor variants with abdominal obesity in American Indians: the Strong Heart Family Study.
abstract: Cigarette smoke is a strong risk factor for obesity and cardiovascular disease. The effect of genetic variants involved in nicotine metabolism on obesity or body composition has not been well studied. Though many genetic variants have previously been associated with adiposity or body fat distribution, a single variant usually confers a minimal individual risk. The goal of this study is to evaluate the joint association of multiple variants involved in cigarette smoke or nicotine dependence with obesity-related phenotypes in American Indians. To achieve this goal, we genotyped 61 tagSNPs in seven genes encoding nicotine acetylcholine receptors (nAChRs) in 3,665 American Indians participating in the Strong Heart Family Study. Single SNP association with obesity-related traits was tested using family-based association, adjusting for traditional risk factors including smoking. Joint association of all SNPs in the seven nAChRs genes were examined by gene-family analysis based on weighted truncated product method (TPM). Multiple testing was controlled by false discovery rate (FDR). Results demonstrate that multiple SNPs showed weak individual association with one or more measures of obesity, but none survived correction for multiple testing. However, gene-family analysis revealed significant associations with waist circumference (p = 0.0001) and waist-to-hip ratio (p = 0.0001), but not body mass index (p = 0.20) and percent body fat (p = 0.29), indicating that genetic variants are jointly associated with abdominal, but not general, obesity among American Indians. The observed combined genetic effect is independent of cigarette smoking per se. In conclusion, multiple variants in the nAChR gene family are jointly associated with abdominal obesity in American Indians, independent of general obesity and cigarette smoking per se.
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Fawn
authors.initials: F
authors.lastname: Yeh
authors.affiliation: Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Lee
authors.affiliation: MedStar Health Research Institute, Hyattsville, Maryland, United States of America; Georgetown and Howard Universities Centers for Translational Sciences, Washington, District of Columbia, United States of America.
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050218:Body Fat Distribution; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000208:ethnology* / Q000209:etiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000453:epidemiology / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult
chemical_list: D011978:Receptors, Nicotinic