Distinguishing population stratification from genuine allelic effects with Mx: Association of ADH2 with alcohol consumption

M. C. Neale; S. S. Cherny; P. C. Sham; J. B. Whitfield; A. C. Heath; A. J. Birley; N. G. Martin

doi:10.1023/A:1021638122693

Distinguishing population stratification from genuine allelic effects with Mx: Association of ADH2 with alcohol consumption

M. C. Neale^*, S. S. Cherny, P. C. Sham, J. B. Whitfield, A. C. Heath, A. J. Birley, N. G. Martin

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

A universal problem in genetic association studies is to distinguish associations due to genuine effects of the locus under investigation, or linkage disequilibrium with a nearby locus that has a genuine effect, from associations due to population stratification or other artifacts. Fulker et al. (1999) have suggested a test using unselected sib pairs to distinguish these two causes of association. The test is readily implemented within a standard maximum-likelihood framework using the Mx package. The approach is applied to data on ADH2 genotypes and a measure of alcohol consumption from an Australian DZ twin pair sample. Results indicate that the association of the ADH2*2 allele with lower alcohol consumption cannot be explained by simple admixture and that there may be genuine allelic effects of the locus on alcohol consumption. Power calculations are provided to show that these results are plausible for the sample size in this study and consider the effects of genetic architecture and sample structure on required sample sizes for the Fulker et al. test.

Original language	English
Pages (from-to)	233-243
Number of pages	11
Journal	Behavior Genetics
Volume	29
Issue number	4
DOIs	https://doi.org/10.1023/A:1021638122693
State	Published - 1999
Externally published	Yes

Funding

Funders	Funder number
Cambridge UK
Gemini Holdings PLC
National Institute of Mental Health	MH-01458
National Institute on Drug Abuse	EY-12562, DA-11015
National Institute on Alcohol Abuse and Alcoholism	AA07728, AA07535 AA10249
National Health and Medical Research Council
Mauritius Research Council

Keywords

ADH2
Admixture
Alcohol consumption
Genetic association
Identical by descent (IBD)
Linkage
Linkage disequilibrium
Mx
Population stratification
Statistical model
Twins

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10.1023/A:1021638122693

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@article{4059707e0bad4c8da75988acd5716c1f,

title = "Distinguishing population stratification from genuine allelic effects with Mx: Association of ADH2 with alcohol consumption",

abstract = "A universal problem in genetic association studies is to distinguish associations due to genuine effects of the locus under investigation, or linkage disequilibrium with a nearby locus that has a genuine effect, from associations due to population stratification or other artifacts. Fulker et al. (1999) have suggested a test using unselected sib pairs to distinguish these two causes of association. The test is readily implemented within a standard maximum-likelihood framework using the Mx package. The approach is applied to data on ADH2 genotypes and a measure of alcohol consumption from an Australian DZ twin pair sample. Results indicate that the association of the ADH2*2 allele with lower alcohol consumption cannot be explained by simple admixture and that there may be genuine allelic effects of the locus on alcohol consumption. Power calculations are provided to show that these results are plausible for the sample size in this study and consider the effects of genetic architecture and sample structure on required sample sizes for the Fulker et al. test.",

keywords = "ADH2, Admixture, Alcohol consumption, Genetic association, Identical by descent (IBD), Linkage, Linkage disequilibrium, Mx, Population stratification, Statistical model, Twins",

author = "Neale, {M. C.} and Cherny, {S. S.} and Sham, {P. C.} and Whitfield, {J. B.} and Heath, {A. C.} and Birley, {A. J.} and Martin, {N. G.}",

note = "Funding Information: This work was supported by NHMRC (Australia) grants to N. G. M. and J. B. W.; NIAAA Grants AA07535 AA10249, and AA07728 to A. C. H.; NIDA Grant DA-11015 to D. W. F. and S. S. C.; EY-12562 and MRC (England) grants to D. W. F., P. C. S., and S. S. C.; NIMH Grant MH-01458; and a grant from Gemini Holdings PLC,Cambridge UK, to M. C. N. The authors are grateful for comments from two anonymous reviewers and the editor M. Miller which greatly improved this paper.",

year = "1999",

doi = "10.1023/A:1021638122693",

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journal = "Behavior Genetics",

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TY - JOUR

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T2 - Association of ADH2 with alcohol consumption

AU - Neale, M. C.

AU - Cherny, S. S.

AU - Sham, P. C.

AU - Whitfield, J. B.

AU - Heath, A. C.

AU - Birley, A. J.

AU - Martin, N. G.

N1 - Funding Information: This work was supported by NHMRC (Australia) grants to N. G. M. and J. B. W.; NIAAA Grants AA07535 AA10249, and AA07728 to A. C. H.; NIDA Grant DA-11015 to D. W. F. and S. S. C.; EY-12562 and MRC (England) grants to D. W. F., P. C. S., and S. S. C.; NIMH Grant MH-01458; and a grant from Gemini Holdings PLC,Cambridge UK, to M. C. N. The authors are grateful for comments from two anonymous reviewers and the editor M. Miller which greatly improved this paper.

PY - 1999

Y1 - 1999

N2 - A universal problem in genetic association studies is to distinguish associations due to genuine effects of the locus under investigation, or linkage disequilibrium with a nearby locus that has a genuine effect, from associations due to population stratification or other artifacts. Fulker et al. (1999) have suggested a test using unselected sib pairs to distinguish these two causes of association. The test is readily implemented within a standard maximum-likelihood framework using the Mx package. The approach is applied to data on ADH2 genotypes and a measure of alcohol consumption from an Australian DZ twin pair sample. Results indicate that the association of the ADH2*2 allele with lower alcohol consumption cannot be explained by simple admixture and that there may be genuine allelic effects of the locus on alcohol consumption. Power calculations are provided to show that these results are plausible for the sample size in this study and consider the effects of genetic architecture and sample structure on required sample sizes for the Fulker et al. test.

AB - A universal problem in genetic association studies is to distinguish associations due to genuine effects of the locus under investigation, or linkage disequilibrium with a nearby locus that has a genuine effect, from associations due to population stratification or other artifacts. Fulker et al. (1999) have suggested a test using unselected sib pairs to distinguish these two causes of association. The test is readily implemented within a standard maximum-likelihood framework using the Mx package. The approach is applied to data on ADH2 genotypes and a measure of alcohol consumption from an Australian DZ twin pair sample. Results indicate that the association of the ADH2*2 allele with lower alcohol consumption cannot be explained by simple admixture and that there may be genuine allelic effects of the locus on alcohol consumption. Power calculations are provided to show that these results are plausible for the sample size in this study and consider the effects of genetic architecture and sample structure on required sample sizes for the Fulker et al. test.

KW - ADH2

KW - Admixture

KW - Alcohol consumption

KW - Genetic association

KW - Identical by descent (IBD)

KW - Linkage

KW - Linkage disequilibrium

KW - Mx

KW - Population stratification

KW - Statistical model

KW - Twins

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SN - 0001-8244

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EP - 243

JO - Behavior Genetics

JF - Behavior Genetics

IS - 4

ER -

Distinguishing population stratification from genuine allelic effects with Mx: Association of ADH2 with alcohol consumption

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