title: Genetic variants in nicotinic acetylcholine receptor genes jointly contribute to kidney function in American Indians: the Strong Heart Family Study.
abstract: BACKGROUND
  Cigarette smoking negatively affects kidney function. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with nicotine dependence, and are likely to influence renal function and related traits. Whereas each single variant may only exert a small effect, the joint contribution of multiple variants to the risk of disease could be substantial.
  
  
  METHODS
  Using a gene-family approach, we investigated the joint association of 61 tagging SNPs in seven genes encoding the nAChRs with kidney function in 3620 American Indians participating in the Strong Heart Family Study, independent of known risk factors. Kidney function was evaluated by estimated glomerular filtration rate, urinary albumin/creatinine ratio, albuminuria and chronic kidney disease. The joint impact of smoking-related variants was assessed using the weighted truncated product method.
  
  
  RESULTS
  Multiple SNPs showed marginal individual effect on renal function variability, and only a few survive multiple comparison correction. In contrast, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant associations of the nAChR gene family with kidney function variables including estimated glomerular filtration rate, urinary albumin/creatinine ratio, and albuminuria (all Ps ≤ 0.0001) after adjusting for established risk factors including cigarette smoking.
  
  
  CONCLUSIONS
  Genetic variants in nAChR genes jointly contribute to renal function or kidney damage in American Indians. The effects of these genetic variants on kidney function or damage are independent of traditional risk factors including cigarette smoking per se.
authors.affiliation: aTulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana bRush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois cTexas Biomedical Research Institute, San Antonio, Texas dMedStar Health Research Institute, Hyattsville, Maryland eUniversity of North Carolina at Chapel Hill, Chapel Hill, North Carolina fCenter for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.forename: Shengxu
authors.initials: S
authors.lastname: Li
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Lee
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000328:Adult; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007198:Indians, North American; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D011978:Receptors, Nicotinic