TY  - BOOK
AU  - Howard, Barbara V
TI  - Joint associations of 61 genetic variants in the nicotinic acetylcholine receptor genes with subclinical atherosclerosis in American Indians: a gene-family analysis
SN  - 1942-3268
KW  - *Atherosclerosis/ge [Genetics]
KW  - *Genetic Variation
KW  - *Indians, North American/ge [Genetics]
KW  - *Multigene Family
KW  - *Receptors, Nicotinic/ge [Genetics]
KW  - Adult
KW  - Atherosclerosis/pp [Physiopathology]
KW  - Carotid Intima-Media Thickness
KW  - Female
KW  - Genetic Predisposition to Disease
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Pedigree
KW  - Polymorphism, Single Nucleotide
KW  - Prospective Studies
KW  - Risk Factors
KW  - MedStar Health Research Institute
KW  - Journal Article
KW  - Multicenter Study
KW  - Research Support, N.I.H., Extramural
N2  - BACKGROUND: Atherosclerosis is the underlying cause of cardiovascular disease, the leading cause of morbidity and mortality in all American populations, including American Indians. Genetic factors play an important role in the pathogenesis of atherosclerosis. Although a single-nucleotide polymorphism (SNP) may explain only a small portion of variability in disease, the joint effect of multiple variants in a pathway on disease susceptibility could be large; CONCLUSIONS: Genetic variants in the nicotinic acetylcholine receptor gene family jointly contribute to subclinical atherosclerosis in American Indians who participated in the SHFS. These variants may influence the susceptibility of atherosclerosis through pathways other than cigarette smoking per se; METHODS AND RESULTS: Using a gene-family analysis, we investigated the joint associations of 61 tag SNPs in 7 nicotinic acetylcholine receptor genes with subclinical atherosclerosis, as measured by carotid intima-media thickness and plaque score, in 3665 American Indians from 94 families recruited by the Strong Heart Family Study (SHFS). Although multiple SNPs showed marginal association with intima-media thickness and plaque score individually, only a few survived adjustments for multiple testing. However, simultaneously modeling of the joint effect of all 61 SNPs in 7 nicotinic acetylcholine receptor genes revealed significant association of the nicotinic acetylcholine receptor gene family with both intima-media thickness and plaque score independent of known coronary risk factors
UR  - http://dx.doi.org/10.1161/CIRCGENETICS.112.963967
ER  -