Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population

Michael Way; Andrew McQuillin; Jit Saini; Kush Ruparelia; Gregory J. Lydall; Irene Guerrini; David Ball; Iain Smith; Giorgia Quadri; Allan D. Thomson; Katherine Kasiakogia-Worlley; Raquin Cherian; Priyanthi Gunwardena; Harish Rao; Girija Kottalgi; Shamir Patel; Audrey Hillman; Ewen Douglas; Sherhzad Y. Qureshi; Gerry Reynolds; Sameer Jauhar; Aideen O'Kane; Alex Dedman; Sally Sharp; Radhika Kandaswamy; Karim Dar; David Curtis; Marsha Y. Morgan; Hugh M D Gurling

doi:10.1111/adb.12141

Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population

Michael Way, Andrew McQuillin, Jit Saini, Kush Ruparelia, Gregory J. Lydall, Irene Guerrini, David Ball, Iain Smith, Giorgia Quadri, Allan D. Thomson, Katherine Kasiakogia-Worlley, Raquin Cherian, Priyanthi Gunwardena, Harish Rao, Girija Kottalgi, Shamir Patel, Audrey Hillman, Ewen Douglas, Sherhzad Y. Qureshi, Gerry ReynoldsSameer Jauhar, Aideen O'Kane, Alex Dedman, Sally Sharp, Radhika Kandaswamy, Karim Dar, David Curtis, Marsha Y. Morgan^*, Hugh M D Gurling

^*Corresponding author for this work

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

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Abstract

Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10^-6, odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10^-5, OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

Original language	English
Pages (from-to)	594-604
Number of pages	11
Journal	Addiction Biology
Volume	20
Issue number	3
Early online date	16 Apr 2014
DOIs	https://doi.org/10.1111/adb.12141
Publication status	Published - 1 May 2015

Keywords

Alcohol dehydrogenase
alcohol dependence
association study
British and Irish ancestry
population attributable risk
protective alleles

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10.1111/adb.12141

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Way, M., McQuillin, A., Saini, J., Ruparelia, K., Lydall, G. J., Guerrini, I., Ball, D., Smith, I., Quadri, G., Thomson, A. D., Kasiakogia-Worlley, K., Cherian, R., Gunwardena, P., Rao, H., Kottalgi, G., Patel, S., Hillman, A., Douglas, E., Qureshi, S. Y., ... Gurling, H. M. D. (2015). Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population. Addiction Biology, 20(3), 594-604. https://doi.org/10.1111/adb.12141

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title = "Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population",

abstract = "Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10-6, odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10-5, OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.",

keywords = "Alcohol dehydrogenase, alcohol dependence, association study, British and Irish ancestry, population attributable risk, protective alleles",

author = "Michael Way and Andrew McQuillin and Jit Saini and Kush Ruparelia and Lydall, {Gregory J.} and Irene Guerrini and David Ball and Iain Smith and Giorgia Quadri and Thomson, {Allan D.} and Katherine Kasiakogia-Worlley and Raquin Cherian and Priyanthi Gunwardena and Harish Rao and Girija Kottalgi and Shamir Patel and Audrey Hillman and Ewen Douglas and Qureshi, {Sherhzad Y.} and Gerry Reynolds and Sameer Jauhar and Aideen O'Kane and Alex Dedman and Sally Sharp and Radhika Kandaswamy and Karim Dar and David Curtis and Morgan, {Marsha Y.} and Gurling, {Hugh M D}",

year = "2015",

month = may,

day = "1",

doi = "10.1111/adb.12141",

language = "English",

volume = "20",

pages = "594--604",

journal = "Addiction Biology",

issn = "1355-6215",

publisher = "Wiley-Blackwell",

number = "3",

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Way, M, McQuillin, A, Saini, J, Ruparelia, K, Lydall, GJ, Guerrini, I , Ball, D, Smith, I, Quadri, G, Thomson, AD, Kasiakogia-Worlley, K, Cherian, R, Gunwardena, P, Rao, H, Kottalgi, G, Patel, S, Hillman, A, Douglas, E, Qureshi, SY, Reynolds, G, Jauhar, S, O'Kane, A, Dedman, A, Sharp, S, Kandaswamy, R, Dar, K, Curtis, D, Morgan, MY & Gurling, HMD 2015, 'Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population', Addiction Biology, vol. 20, no. 3, pp. 594-604. https://doi.org/10.1111/adb.12141

TY - JOUR

T1 - Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population

AU - Way, Michael

AU - McQuillin, Andrew

AU - Saini, Jit

AU - Ruparelia, Kush

AU - Lydall, Gregory J.

AU - Guerrini, Irene

AU - Ball, David

AU - Smith, Iain

AU - Quadri, Giorgia

AU - Thomson, Allan D.

AU - Kasiakogia-Worlley, Katherine

AU - Cherian, Raquin

AU - Gunwardena, Priyanthi

AU - Rao, Harish

AU - Kottalgi, Girija

AU - Patel, Shamir

AU - Hillman, Audrey

AU - Douglas, Ewen

AU - Qureshi, Sherhzad Y.

AU - Reynolds, Gerry

AU - Jauhar, Sameer

AU - O'Kane, Aideen

AU - Dedman, Alex

AU - Sharp, Sally

AU - Kandaswamy, Radhika

AU - Dar, Karim

AU - Curtis, David

AU - Morgan, Marsha Y.

AU - Gurling, Hugh M D

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10-6, odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10-5, OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

AB - Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10-6, odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10-5, OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

KW - Alcohol dehydrogenase

KW - alcohol dependence

KW - association study

KW - British and Irish ancestry

KW - population attributable risk

KW - protective alleles

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U2 - 10.1111/adb.12141

DO - 10.1111/adb.12141

M3 - Article

C2 - 24735490

AN - SCOPUS:84926529602

SN - 1355-6215

VL - 20

SP - 594

EP - 604

JO - Addiction Biology

JF - Addiction Biology

IS - 3

ER -

Genetic variants in or near adh1b and adh1c affect susceptibility to alcohol dependence in a british and irish population

Abstract

Keywords

UN SDGs

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