Confirmation of prior evidence of genetic susceptibility to alcoholism in a genome-wide association study of comorbid alcoholism and bipolar disorder

被引：52

作者：

Lydall, Gregory John ^{[1
]}

Bass, Nicholas J. ^{[1
]}

McQuillin, Andrew ^{[1
]}

Lawrence, Jacob ^{[1
]}

Anjorin, Adebayo ^{[1
]}

Kandaswamy, Radhika ^{[1
]}

Pereira, Ana ^{[1
]}

Guerrini, Irene ^{[1
]}

Curtis, David ^{[2
]}

Vine, Anna E. ^{[2
]}

Sklar, Pamela ^{[3
,4
,5
,6
,7
,8
]}

Purcell, Shaun M. ^{[3
,4
,5
,6
,7
,8
]}

Gurling, Hugh Malcolm Douglas ^{[1
]}

机构：

[1] UCL, Mol Psychiat Lab, Dept Mental Hlth Sci, London W1T 4JF, England

[2] Univ London, Barts & London Sch Med & Dent, Ctr Psychiat, London, England

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[5] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[6] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Dept Med, Boston, MA USA

[8] Broad Inst Harvard & MIT, Cambridge, MA USA

来源：

PSYCHIATRIC GENETICS | 2011年 / 21卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

alcoholism; bipolar; comorbid; gene wise; genome-wide association; AFFECTED SIB PAIR; HISTAMINE N-METHYLTRANSFERASE; ADDICTION MOLECULAR-GENETICS; D-2; DOPAMINE-RECEPTOR; DRUG-DEPENDENCE; LINKAGE ANALYSIS; SUBSTANCE DEPENDENCE; CANDIDATE GENES; FUNCTIONAL POLYMORPHISM; PROMOTER POLYMORPHISMS;

D O I：

10.1097/YPG.0b013e32834915c2

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Objectives Alcoholism and affective disorders are both strongly comorbid and heritable. We have investigated the genetic comorbidity between bipolar affective disorder and alcoholism. Methods A genome-wide allelic association study of 506 patients from the University College London bipolar disorder case-control sample and 510 ancestrally matched supernormal controls. One hundred forty-three of the bipolar patients fulfilled the Research Diagnostic Criteria diagnosis of alcoholism. A total of 372 193 single nucleotide polymorphisms (SNPs) were genotyped. Genes previously shown to be associated with alcoholism and addiction phenotypes were then tested for association in the bipolar alcoholic sample using gene-wise permutation tests of all SNPs genotyped within a 50-kb region flanking each gene. Results Several central nervous system genes showed significant (P<0.05) gene-wise evidence of association with bipolar alcoholism. The genes implicated, which replicated genes previously shown to be associated with alcoholism were: cadherin 11, collagen type 11 alpha 2, neuromedin U receptor 2, exportin7, and semaphorin-associated protein 5A. The SNPs most strongly implicated in bipolar alcoholism, but, which did not meet conventional genome-wide significance criteria were the insulin-like growth factor-binding protein 7, carboxypeptidase O, cerebellin 2, and the cadherin 12 genes. Conclusion We have confirmed the role of some genes previously shown to be associated with alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup, bipolar disorder may lower the threshold for the phenotypic expression of these alcoholism susceptibility genes. We also show that some genes may independently increase susceptibility to affective disorder and alcoholism. Psychiatr Genet 21: 294-306 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Psychiatric Genetics 2011, 21: 294-306

引用

页码：294 / 306

页数：13

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