Genome-wide association study of pathological gambling

2016 ◽  
Vol 36 ◽  
pp. 38-46 ◽  
Author(s):  
M. Lang ◽  
T. Leménager ◽  
F. Streit ◽  
M. Fauth-Bühler ◽  
J. Frank ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Pathological Gambling ◽  
Huntington's Disease ◽  
Association Study ◽  
Huntington’S Disease ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Genetic Overlap

AbstractBackgroundPathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.MethodsFour hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.ResultsNo genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.ConclusionsThe present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.

scholarly journals Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

2017 ◽  
Vol 16 (9) ◽  
pp. 701-711 ◽  
Author(s):  
Davina J Hensman Moss ◽  
Antonio F Pardiñas ◽  
Douglas Langbehn ◽  
Kitty Lo ◽  
Blair R Leavitt ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Association Study ◽  
Huntington’S Disease ◽  
Disease Progression ◽  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yan Sun ◽  
Suhua Chang ◽  
Fan Wang ◽  
Hongqiang Sun ◽  
Zhaojun Ni ◽  
...  
Keyword(s):  
Alcohol Dependence ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Han Chinese ◽  
Genome Wide Association ◽  
European American ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Functional Snp

Abstract Alcohol-related behaviors are moderately heritable and have ethnic-specific characteristics. At present, genetic studies for alcohol dependence (AD) in Chinese populations are underrepresented. We are the first to conduct a genome-wide association study (GWAS) for AD using 533 male alcoholics and 2848 controls of Han Chinese ethnicity and replicate our findings in 146 male alcoholics and 200 male controls. We then assessed genetic effects on AD characteristics (drinking volume/age onset/Michigan Alcoholism Screening Test (MAST)/Barratt Impulsiveness Scale (BIS-11)), and compared the polygenic risk of AD in Han Chinese with other populations (Thai, European American and African American). We found and validated two significant loci, one located in 4q23, with lead SNP rs2075633*ADH1B (Pdiscovery = 6.64 × 10−16) and functional SNP rs1229984*ADH1B (Pdiscovery = 3.93 × 10−13); and the other located in 12q24.12-12q24.13, with lead SNP rs11066001*BRAP (Pdiscovery = 1.63 × 10−9) and functional SNP rs671*ALDH2 (Pdiscovery = 3.44 × 10−9). ADH1B rs1229984 was associated with MAST, BIS_total score and average drinking volume. Polygenic risk scores from the Thai AD and European American AD GWAS were significantly associated with AD in Han Chinese, which were entirely due to the top two loci, however there was no significant prediction from African Americans. This is the first case-control AD GWAS in Han Chinese. Our findings demonstrate that these variants, which were highly linked with ALDH2 rs671 and ADH1B rs1229984, were significant modulators for AD in our Han Chinese cohort. A larger replication cohort is still needed to validate our findings.

scholarly journals Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis

2019 ◽  
Author(s):  
Richard J Allen ◽  
Beatriz Guillen-Guio ◽  
Justin M Oldham ◽  
Shwu-Fan Ma ◽  
Amy Dressen ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Telomere Maintenance ◽  
Genome Wide Association ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Genome Wide

AbstractRationaleIdiopathic pulmonary fibrosis (IPF) is a complex lung disease characterised by scarring of the lung that is believed to result from an atypical response to injury of the epithelium. The mechanisms by which this arises are poorly understood and it is likely that multiple pathways are involved. The strongest genetic association with IPF is a variant in the promoter of MUC5B where each copy of the risk allele confers a five-fold risk of disease. However, genome-wide association studies have reported additional signals of association implicating multiple pathways including host defence, telomere maintenance, signalling and cell-cell adhesion.ObjectivesTo improve our understanding of mechanisms that increase IPF susceptibility by identifying previously unreported genetic associations.Methods and measurementsWe performed the largest genome-wide association study undertaken for IPF susceptibility with a discovery stage comprising up to 2,668 IPF cases and 8,591 controls with replication in an additional 1,467 IPF cases and 11,874 controls. Polygenic risk scores were used to assess the collective effect of variants not reported as associated with IPF.Main resultsWe identified and replicated three new genome-wide significant (P<5×10-8) signals of association with IPF susceptibility (near KIF15, MAD1L1 and DEPTOR) and confirm associations at 11 previously reported loci. Polygenic risk score analyses showed that the combined effect of many thousands of as-yet unreported IPF risk variants contribute to IPF susceptibility.ConclusionsNovel association signals support the importance of mTOR signalling in lung fibrosis and suggest a possible role of mitotic spindle-assembly genes in IPF susceptibility.

scholarly journals Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

2020 ◽  
Vol 52 (12) ◽  
pp. 1303-1313
Author(s):  
Mark K. Bakker ◽  
◽  
Rick A. A. van der Spek ◽  
Wouter van Rheenen ◽  
Sandrine Morel ◽  
...  
Keyword(s):  
Risk Factors ◽  
Association Study ◽  
Intracranial Aneurysms ◽  
Genome Wide Association Study ◽  
Clinical Risk Factors ◽  
Genome Wide Association ◽  
Clinical Risk ◽  
Genome Wide ◽  
Genetic Overlap

scholarly journals Genome-wide association study of body mass index in subjects with alcohol dependence

2015 ◽  
Vol 22 (2) ◽  
pp. 535-549 ◽  
Author(s):  
Renato Polimanti ◽  
Huiping Zhang ◽  
Andrew H. Smith ◽  
Hongyu Zhao ◽  
Lindsay A. Farrer ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Alcohol Dependence ◽  
Association Study ◽  
Body Mass ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals Genome-Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders

2013 ◽  
Vol 65 (12) ◽  
pp. 3239-3247 ◽  
Author(s):  
Frederick W. Miller ◽  
Robert G. Cooper ◽  
Jiří Vencovský ◽  
Lisa G. Rider ◽  
Katalin Danko ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Autoimmune Disorders ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Genetic Overlap

scholarly journals Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112,117)

2017 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
Gail Davies ◽  
David M. Howard ◽  
Lynsey S. Hall ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Hdl Cholesterol ◽  
Genome Wide Association ◽  
P Value ◽  
Uk Biobank ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Overlap

AbstractAlcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well known genetic variants in alcohol metabolizing genes, e.g. ALDH2, ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 8 independent loci. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, PXDN, CADM2 and TNFRSF11A. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (CRHR1, DRD2), and genes previously associated with alcohol consumption (AUTS2). GCTA-GREML analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (S.E.=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation between male and female alcohol consumption was 0.73 (S.E.=0.09, p-value = 1.37 x 10−16). Using LD score regression, genetic overlap was found between alcohol consumption and schizophrenia (rG=0.13, S.E=0.04), HDL cholesterol (rG=0.21, S.E=0.05), smoking (rG=0.49, S.E=0.06) and various anthropometric traits (e.g. Overweight, rG=-0.19, S.E.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies 4 novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

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