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PW01-233 - Searching For Alcoholism Vulnerability Genes: Uk-Coga Provisional Clinical Findings

Published online by Cambridge University Press:  17 April 2020

G. Lydall ,
K. Worlley ,
A. McQuillin ,
S. Jauhar ,
A. O’Kane ,
H. Rao ,
A. Anjorin ,
I. Guerrini ,
D. Curtis  and
A.E. Vine
...Show all authors
G. Lydall
Affiliation:
Molecular Psychiatry, University College London, London, UK
K. Worlley
Affiliation:
Molecular Psychiatry, University College London, London, UK
A. McQuillin
Affiliation:
Molecular Psychiatry, University College London, London, UK
S. Jauhar
Affiliation:
Molecular Psychiatry, University College London, London, UK
A. O’Kane
Affiliation:
Molecular Psychiatry, University College London, London, UK
H. Rao
Affiliation:
Molecular Psychiatry, University College London, London, UK
A. Anjorin
Affiliation:
Molecular Psychiatry, University College London, London, UK
I. Guerrini
Affiliation:
Molecular Psychiatry, University College London, London, UK
D. Curtis
Affiliation:
Molecular Psychiatry, University College London, London, UK
A.E. Vine
Affiliation:
Molecular Psychiatry, University College London, London, UK
H.M. Gurling
Affiliation:
Molecular Psychiatry, University College London, London, UK

Abstract

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Background

Alcoholism has a high prevalence and impacts on morbidity, mortality, life quality, and the economy. Heritability estimates of alcohol dependence are 50-61%. Putative psychological, cultural, and genetic susceptibilities to alcoholism have been identified but understanding of the genetic components is still underdeveloped.

Aim

Identify genetic vulnerabilities predisposing individuals to alcoholism and co-morbid psychiatric disorders in the largest study of its kind.

Method

12 centres including 10 trainees are currently collecting blood and clinical samples. Nearly 1700 of 2000 cases of ICD-10/DSM-IV alcohol dependence have been collected; 500 with standardized assessments of alcohol use and comorbdity; and 2000 ancestrally-matched supernormal controls from UCL/collaborators. Genomic DNA will be isolated following standard procedures. Genotyping will be performed using the Affymetrix Gene Chip Human Mapping 1M Array to type up to 1 million single nucleotide polymorphism (SNP) and copy number variant (CNV) markers. Chi-square analysis of allelic association for the alcoholic sample versus controls will occur.

Results

n=65; 57% male; mean age 45years; mean age onset harmful alcohol use 19years; mean age onset withdrawals 32y; mean alcohol intake 21 units; primary depression 27%; secondary depression 49%; antisocial personality disorder 14%. The candidate gene approach in this sample has shown that the GABA receptor B1 (GABRB1) and the tachykinin receptor 1 (TACR1) are involved in genetic susceptibility to alcoholism. The D2 dopamine receptor is next.

Conclusion

Preliminary data suggests high psychiatric comorbidity in a clinical alcohol dependence sample and implicated candidate genes. Next is genomewide analysis of markers, sequencing and biological pathway/systems alterations.

Type
Substance related disorders
Information
European Psychiatry , Volume 25 , Issue S1: 18th European Congress of Psychiatry. February 27, March 2, 2010 - Munich, Germany , 2010 , 25-E1640
Copyright
Copyright © European Psychiatric Association 2009
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