NDLI: Uncovering hidden variance: pair-wise SNP analysis accounts for additional variance in nicotine dependence

Content Provider	Springer Nature Link
Author	Culverhouse, Robert C. Saccone, Nancy L. Stitzel, Jerry A. Wang, Jen C. Steinbach, Joseph H. Goate, Alison M. Schwantes An, Tae Hwi Grucza, Richard A. Stevens, Victoria L. Bierut, Laura J.
Copyright Year	2010
Abstract	Results from genome-wide association studies of complex traits account for only a modest proportion of the trait variance predicted to be due to genetics. We hypothesize that joint analysis of polymorphisms may account for more variance. We evaluated this hypothesis on a case–control smoking phenotype by examining pairs of nicotinic receptor single-nucleotide polymorphisms (SNPs) using the Restricted Partition Method (RPM) on data from the Collaborative Genetic Study of Nicotine Dependence (COGEND). We found evidence of joint effects that increase explained variance. Four signals identified in COGEND were testable in independent American Cancer Society (ACS) data, and three of the four signals replicated. Our results highlight two important lessons: joint effects that increase the explained variance are not limited to loci displaying substantial main effects, and joint effects need not display a significant interaction term in a logistic regression model. These results suggest that the joint analyses of variants may indeed account for part of the genetic variance left unexplained by single SNP analyses. Methodologies that limit analyses of joint effects to variants that demonstrate association in single SNP analyses, or require a significant interaction term, will likely miss important joint effects.
Starting Page	177
Ending Page	188
Page Count	12
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	129
Issue Number	2
e-ISSN	14321203
Language	English
Publisher	Springer-Verlag
Publisher Date	2010-11-16
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Metabolic Diseases Gene Function Molecular Medicine
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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