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A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.

Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence,... Full description

Journal Title: Human genetics October 2013, Vol.132(10), pp.1141-1151
Main Author: Kapoor, Manav
Other Authors: Wang, Jen-Chyong , Wetherill, Leah , Le, Nhung , Bertelsen, Sarah , Hinrichs, Anthony L , Budde, John , Agrawal, Arpana , Bucholz, Kathleen , Dick, Danielle , Harari, Oscar , Hesselbrock, Victor , Kramer, John , Nurnberger, John I , Rice, John , Saccone, Nancy , Schuckit, Marc , Tischfield, Jay , Porjesz, Bernice , Edenberg, Howard J , Bierut, Laura , Foroud, Tatiana , Goate, Alison
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1432-1203 ; DOI: 10.1007/s00439-013-1318-z
Link: http://search.proquest.com/docview/1433268190/?pq-origsite=primo
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title: A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
format: Article
creator:
  • Kapoor, Manav
  • Wang, Jen-Chyong
  • Wetherill, Leah
  • Le, Nhung
  • Bertelsen, Sarah
  • Hinrichs, Anthony L
  • Budde, John
  • Agrawal, Arpana
  • Bucholz, Kathleen
  • Dick, Danielle
  • Harari, Oscar
  • Hesselbrock, Victor
  • Kramer, John
  • Nurnberger, John I
  • Rice, John
  • Saccone, Nancy
  • Schuckit, Marc
  • Tischfield, Jay
  • Porjesz, Bernice
  • Edenberg, Howard J
  • Bierut, Laura
  • Foroud, Tatiana
  • Goate, Alison
subjects:
  • Adult–Genetics
  • Alcohol Drinking–Genetics
  • Alcoholism–Genetics
  • Chromosomes, Human, Pair 13–Genetics
  • DNA-Binding Proteins–Methods
  • Female–Genetics
  • Gene-Environment Interaction–Genetics
  • Genetic Loci–Genetics
  • Genetic Predisposition to Disease–Genetics
  • Genetics, Population–Genetics
  • Genome, Human–Genetics
  • Genome-Wide Association Study–Genetics
  • Humans–Genetics
  • Lim Domain Proteins–Genetics
  • Male–Genetics
  • Middle Aged–Genetics
  • Pedigree–Genetics
  • Phenotype–Genetics
  • Phosphoinositide Phospholipase C–Genetics
  • Polymorphism, Single Nucleotide–Genetics
  • Transcription Factors–Genetics
  • DNA-Binding Proteins
  • Lim Domain Proteins
  • Lmo1 Protein, Human
  • Transcription Factors
  • Phosphoinositide Phospholipase C
  • Phospholipase C Epsilon
ispartof: Human genetics, October 2013, Vol.132(10), pp.1141-1151
description: Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 x [10.sup.-6]) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 x [10.sup.-7]), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 x [10.sup.-7]) and PLCL1 genes (p = 4.1 x [10.sup.-6]) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p [less than or equal to] [10.sup.-4]) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 x [10.sup.-3], 3 x [10.sup.-6]), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.
language: eng
source:
identifier: E-ISSN: 1432-1203 ; DOI: 10.1007/s00439-013-1318-z
fulltext: fulltext
issn:
  • 14321203
  • 1432-1203
url: Link


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titleA meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
creatorKapoor, Manav ; Wang, Jen-Chyong ; Wetherill, Leah ; Le, Nhung ; Bertelsen, Sarah ; Hinrichs, Anthony L ; Budde, John ; Agrawal, Arpana ; Bucholz, Kathleen ; Dick, Danielle ; Harari, Oscar ; Hesselbrock, Victor ; Kramer, John ; Nurnberger, John I ; Rice, John ; Saccone, Nancy ; Schuckit, Marc ; Tischfield, Jay ; Porjesz, Bernice ; Edenberg, Howard J ; Bierut, Laura ; Foroud, Tatiana ; Goate, Alison
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ispartofHuman genetics, October 2013, Vol.132(10), pp.1141-1151
identifierE-ISSN: 1432-1203 ; DOI: 10.1007/s00439-013-1318-z
subjectAdult–Genetics ; Alcohol Drinking–Genetics ; Alcoholism–Genetics ; Chromosomes, Human, Pair 13–Genetics ; DNA-Binding Proteins–Methods ; Female–Genetics ; Gene-Environment Interaction–Genetics ; Genetic Loci–Genetics ; Genetic Predisposition to Disease–Genetics ; Genetics, Population–Genetics ; Genome, Human–Genetics ; Genome-Wide Association Study–Genetics ; Humans–Genetics ; Lim Domain Proteins–Genetics ; Male–Genetics ; Middle Aged–Genetics ; Pedigree–Genetics ; Phenotype–Genetics ; Phosphoinositide Phospholipase C–Genetics ; Polymorphism, Single Nucleotide–Genetics ; Transcription Factors–Genetics ; DNA-Binding Proteins ; Lim Domain Proteins ; Lmo1 Protein, Human ; Transcription Factors ; Phosphoinositide Phospholipase C ; Phospholipase C Epsilon
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descriptionMaximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 x [10.sup.-6]) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 x [10.sup.-7]), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 x [10.sup.-7]) and PLCL1 genes (p = 4.1 x [10.sup.-6]) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p [less than or equal to] [10.sup.-4]) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 x [10.sup.-3], 3 x [10.sup.-6]), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.
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15Middle Aged–Genetics
16Pedigree–Genetics
17Phenotype–Genetics
18Phosphoinositide Phospholipase C–Genetics
19Polymorphism, Single Nucleotide–Genetics
20Transcription Factors–Genetics
21DNA-Binding Proteins
22Lim Domain Proteins
23Lmo1 Protein, Human
24Transcription Factors
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26Phospholipase C Epsilon
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titleA meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
authorKapoor, Manav ; Wang, Jen-Chyong ; Wetherill, Leah ; Le, Nhung ; Bertelsen, Sarah ; Hinrichs, Anthony L ; Budde, John ; Agrawal, Arpana ; Bucholz, Kathleen ; Dick, Danielle ; Harari, Oscar ; Hesselbrock, Victor ; Kramer, John ; Nurnberger, John I ; Rice, John ; Saccone, Nancy ; Schuckit, Marc ; Tischfield, Jay ; Porjesz, Bernice ; Edenberg, Howard J ; Bierut, Laura ; Foroud, Tatiana ; Goate, Alison
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6Gene-Environment Interaction–Genetics
7Genetic Loci–Genetics
8Genetic Predisposition to Disease–Genetics
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