期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
卷 168, 期 8, 页码 739-748出版社
WILEY
DOI: 10.1002/ajmg.b.32379
关键词
cohol dependence; heritability; GWAS
资金
- European Research Council (ERC) [284167]
- Netherlands Organisation for Scientific Research (NWO)
- Netherlands Organisation for Health Research and Development (ZonMW)
- EMGO+ Institute for Health and Care Research
- Neuroscience Campus Amsterdam, BBMRI-NL [184.021.007]
- Avera Institute, Sioux Falls, South Dakota (USA)
- ERC [284167, 230374]
- National Institutes of Health [4R37DA018673-06, RC2 MH089951, NIH R01 HD042157-01A1, MH081802, 1RC2 MH089951, 1RC2 MH089995]
- Netherlands Scientific Organization [NWO 480-05-003]
- Dutch Brain Foundation
- Department of Psychology and Education of the VU University Amsterdam
- Netherlands Organization for Scientific Research [ZonMW] [31160008, 940-37-024, NWO/SPI 56-464-14192, NWO-400-05-717, NWO-MW 904-61-19, NWO-MagW 480-04-004, NWO-Veni 016-115-035]
- European Research Council [Genetics of Mental Illness] [ERC-230374]
- Centre for Medical Systems Biology (NWO Genomics)
- Netherlands Bioinformatics Center [BioAssist/RK/2008.024]
- Rutgers University Cell and DNA Repository cooperative agreement [National Institute of Mental Health] [U24 MH068457-06]
- Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health
- ZonMW [10-000-1002]
- Center for Medical Systems Biology (NWO Genomics)
- Biobanking and Biomolecular Resources Research Infrastructure
- EMGO Institute for Health and Care Research
- Neuroscience Campus Amsterdam
- Genetic Association InformationNetwork (GAIN) of the Foundation for the National Institutes of Health
- US National Institute of Mental Health [RC2 MH089951]
- American Recovery and Reinvestment Act
- European Research Council (ERC) [230374] Funding Source: European Research Council (ERC)
Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE = 0.12, P = 0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P = 7.58x10(-7)). This first GWAS of AD using the AUDIT measure found results consistent with previous genetic studies using DSM diagnosis: concordance in heritability estimates and direction of SNPs effect and overlap with top hits from previous GWAS. Thus, the use of appropriate questionnaires may represent cost-effective strategies to phenotype samples in large-scale biobanks or other population-based datasets. (C) 2015 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据