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PW01-232 - Connectivity Genes In Comorbid Alcoholism And Bipolar Disorder

Published online by Cambridge University Press:  17 April 2020

G. Lydall ,
N. Bass ,
A. McQuillin ,
A. Anjorin ,
R. Kandaswamy ,
A.C. Pereira ,
I. Guerrini ,
D. Curtis ,
A.E. Vine  and
P. Sklar
...Show all authors
G. Lydall
Affiliation:
Molecular Psychiatry, University College London, London, UK
N. Bass
Affiliation:
Molecular Psychiatry, University College London, London, UK
A. McQuillin
Affiliation:
Molecular Psychiatry, University College London, London, UK
A. Anjorin
Affiliation:
Molecular Psychiatry, University College London, London, UK
R. Kandaswamy
Affiliation:
Molecular Psychiatry, University College London, London, UK
A.C. Pereira
Affiliation:
Molecular Psychiatry, University College London, London, UK
I. Guerrini
Affiliation:
Molecular Psychiatry, University College London, London, UK
D. Curtis
Affiliation:
Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK
A.E. Vine
Affiliation:
Centre for Psychiatry, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, London, UK
P. Sklar
Affiliation:
Broad Institute, Harvard and MIT, Cambridge, MA, USA
S.M. Purcell
Affiliation:
Broad Institute, Harvard and MIT, Cambridge, MA, USA
H.M. Gurling
Affiliation:
Molecular Psychiatry, University College London, London, UK

Abstract

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Introduction

Bipolar disorder (BPD) and alcoholism are strongly comorbid and both have significant genetic influences but no consistent genetic vulnerability has been found. We aimed to find bipolar-alcoholism vulnerability genes.

Method

A genome-wide association study (GWAS) of 510 patients with bipolar disorder (BPD), of whom 143 met Research Diagnostic Criteria (RDC) alcoholism diagnoses, and 506 ancestrally matched supernormal controls. We genotyped 372K genetic markers on an Affymetrix 500K-array. Chi-square analysis of allelic association using PLINK, and permutation testing for gene-wise association of genes previously associated with alcoholism-related phenotypes using COMBASSOC, were performed.

Results

No marker met genomewide significance. Gene-wise analyses of markers clustering near genes already implicated in alcoholism, but which were not associated in non-alcoholic BPD, were: Cadherin-11 (CDH11, p = 6 × 10-4), Exportin 7 (XPO7), neuromedin-U receptor 2 (NMUR2), collagen type XI-alpha 2 (COL11A2) and Semaphorin-5A (SEMA5A).

Discussion

These genes replicated prior genetic reports implicating “connectivity” (adhesion, migration and neuronal signalling) genes in addictions and comorbid BPD. Connectivity genes regulate neuronal connections during development and play roles in later neuroadaptive and mnemonic processes. These processes may influence addiction vulnerability, as seen clinically in denial, cognitive impairment, and repetitive substance misuse and relapse behaviour. We propose that we have identified genes i) increasing susceptibility to alcoholism that could be unmasked or released by the presence of bipolar affective disorder; ii) and genes increasing susceptibility to affective disorder that also predispose to secondary alcoholism. We were limited by small sample size. Larger future studies are needed.

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-E1639
Copyright
Copyright © European Psychiatric Association 2009
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