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

paper Cited Public

Authors: 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
Year: 2011
Journal: Human genetics
PMID: 21079997
DOI: 10.1007/s00439-010-0911-7
PMCID: PMC3030551

#	Section	Preview
20	Materials and methods — Hypothesis testing — Replication testing	low risk genotypes. We note that although this second replication condition is heuristic, (1) it is…
21	Results — Univariate results	A complete list of the 127 SNPs used in this study, along with the results of the univariate RPM…
22	Results — Pair-wise results	There were a total of 8,001 SNP-pairs analyzed in the hypothesis generating dataset (COGEND). We…
23	Results — Pair-wise results	Each of the joint effect signals in Table 2 involves the SNP rs16969968. This SNP provides the…
24	Results — Pair-wise results	The RPM results are followed in Table 2 by the results from a logistic regression analysis. The…
25	Results — Pair-wise results	Four of the signals listed in Table 2 were testable in the ACS data, and details of the replication…
26	Results — Pair-wise results	The variant rs1696998, though still the most significant SNP in the ACS data, only accounts for…
27	Results — Pair-wise results	Our second ranking of signals, based on increased explained variance under an RPM analysis, was…
28	Results — Pair-wise results	To evaluate how well we succeeded in increasing the explained variance in phenotype, we evaluated…
29	Discussion	Our goal was to determine if examining genetic variants jointly could account for substantially more…
30	Discussion	The prime illustration for both of these points is the joint effect of the loci tagged by rs16969968…
31	Discussion	with the phenotype in a univariate analysis. Again, a joint RPM analysis of the two SNPs accounts…
32	Discussion	The case for these two loci having a synergistic joint effect has been greatly strengthened by…
33	Discussion	by rs588765. The logistic regression interaction term in this analysis was not significant. The…
34	Discussion	Although we cannot know how often this kind of joint effect might occur, we find this result,…
35	Discussion	Although a replicable joint effect does not require a significant logistic regression interaction…
36	Discussion	The variants rs16969968, a non-synonymous coding SNP in CHRNA5, and rs1051730, a synonymous SNP, are…
37	Discussion	similar to those for rs16969968. (An analog of Table 2, replacing rs16969968 throughout with…
38	Discussion	We focused on cholinergic nicotinic receptor subunit genes because the protein products physically…
39	Discussion	We have presented evidence that examining factors jointly, including SNPs displaying little to no…

Name	Type
ACS Cancer Prevention Study-II Nutrition cohort local	cohort
ACS data local	cohort
African American	cohort
age	phenotype
American Community Survey	cohort
binary trait	phenotype
cancer	phenotype
cardiovascular disease	phenotype
CGASP local	cohort
Chinese	cohort
cholinergic nicotinic receptor subunit SNPs local	variant
chr15q25 local	gene
Chrna3	gene
Chrna4	gene
CHRNA5	gene
Chrnb2	gene
Chrnb4	gene
CHRN subunit gene variants local	variant
cigarettes	phenotype
COGEND	cohort
COGEND dataset local	cohort
complex diseases	phenotype
complex traits	phenotype
Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) local	cohort
copy number variant	variant
CYP2A6	gene
datasets	cohort
Detroit	cohort
diabetes	phenotype
dichotomous trait local	phenotype
efficiency of reproduction local	phenotype
European population	cohort
FTND-derived nicotine dependence phenotype local	phenotype
Gabbr1	gene
Gabbr2	gene
genetic data	drug
genetic variants	cohort
gross morphology local	phenotype
HapMap	cohort
heavy drinking	phenotype
heavy smoking phenotype local	phenotype
Heavy-smoking phenotype local	phenotype
heavy versus light smoking phenotype local	phenotype
hypertension	phenotype
Independent Dataset local	cohort
independent samples	cohort
infection	phenotype
Initial Dataset local	cohort
insertion/deletion	variant
inversion	variant
Koreans	cohort
light smokers	phenotype
light smoking phenotype local	phenotype
Light-smoking phenotype local	phenotype
longevity	phenotype
MAOA	gene
mesolimbic reward pathway local	anatomy
Meta-analysis of 76,972 subjects local	cohort
Minneapolis local	cohort
multi-locus genotype local	variant
neuronal nicotinic acetylcholine receptor genes local	gene
nicotine	drug
nicotine dependence	phenotype
nicotine receptor gene cluster local	gene
nicotinic receptor SNP local	variant
nicotinic receptor subunit genes local	gene
nicotinic receptor variants local	variant
Non-dependent smoking local	phenotype
obesity	phenotype
phenotype	phenotype
phenotypic variance	phenotype
Polymorphism	cohort
rare variant	cohort
replication sample	cohort
rs1051730	variant
rs1061730 local	variant
rs13277524	variant
rs1500948 local	variant
rs16969968	variant
rs1696998 local	variant
rs17483548 local	variant
rs2133965 local	variant
rs2292977 local	variant
rs2611603 local	variant
rs3743075 local	variant
rs3787138	variant
rs514743 local	variant
rs588765	variant
rs667282 local	variant
rs680244	variant
sex	phenotype
smoking	phenotype
smoking behavior	phenotype
smoking behaviors	phenotype
SNP	cohort
SNP in CHRNA5-CHRNA3-CHRNB4 cluster local	variant
SNP-pair local	variant
SNPs in cholinergic nicotinic receptor genes local	variant
St. Louis local	cohort
structural variant	cohort
Tobacco and Genetics Consortium	cohort
trait	phenotype
trait variance local	phenotype
translocation	variant
α5α3β4 cluster local	gene

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

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