Characterization of DSM-IV Opioid Dependence Among Individuals of European Ancestry
Characterization of DSM-IV Opioid Dependence Among Individuals of European Ancestry
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DOI：
10.15288/jsad.2019.80.319
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发表时间：
2019-05-01
影响因子：
3.4
通讯作者：
Palmer, Rohan H. C.
中科院分区：
文献类型：
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作者：
Brick, Leslie A.;Micalizzi, Lauren;Palmer, Rohan H. C.
目的：阿片类药物在美国的流行导致了前所未有的发病率和死亡率的增加，造成了严重的公共卫生危机。尽管双胞胎和家庭研究以及全基因组关联研究（GWAS）都确定了导致阿片类药物依赖的重要遗传因素。迄今为止还没有研究估计阿片类药物依赖的基于标记的遗传力估计。本研究的目的是使用一个包含4064名参与者（经过质量控制和输入后）的大型遗传输入的病例/对照样本，使用全基因组数据来估计单核苷酸多态性（snp）标记的无偏遗传力。方法：研究数据是海洛因依赖全基因组研究的一部分，通过基因型和表型数据库（dbGaP）获得。通过调整小等位基因频率（MAF）和连锁不平衡（LD; GREML-LDMS）的基因组关联-矩阵限制最大似然来确定由输入数据中常见snp引起的阿片类药物依赖的变化。在探索性GWAS中使用混合线性模型来评估单个snp的影响。结果：根据第四版《精神障碍诊断与统计手册》，至少45%的阿片类药物依赖差异可归因于常见snp。通过分层来解释基因组中MAF和LD的差异。大多数遗传变异由1%-9% MAF范围内的snp标记，并与该地区的其他snp标记在低LD范围内。LOC I01927293中有2个标记在多次检验校正后存活（即q值< 0.05）。结论：近一半的阿片类药物依赖变异可归因于共同的snp。这种变异大部分是由于低LD与该地区其他标记的罕见变异。
Objective: The opioid epidemic in the United States has led to unprecedented increases in morbidity and mortality, posing a serious public health crisis. Although twin and family studies, as well as genome-wide association studies (GWAS), all identify significant genetic factors contributing to opioid dependence. no studies to date have estimated marker-based heritability estimates of opioid dependence. The goal of the current study was to use a large, genetically imputed, case/control sample of 4,064 participants (after quality control and imputation) with genome-wide data to estimate the unbiased heritability tagged by single nucleotide polymorphisms (SNPs). Method: Study data were part of the Genome-wide Study of Heroin Dependence obtained via the Database for Genotypes and Phenotypes (dbGaP). Genomic-Relatedness-Matrix Restricted Maximum Likelihood with adjustment for minor allele frequency (MAF) and linkage disequilibrium (LD; GREML-LDMS) was used to determine the variation in opioid dependence attributable to common SNPs from imputed data. Mixed linear models were used in an exploratory GWAS to assess effects of single SNPs. Results: At least 45% of the variance in opioid dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, was attributable to common SNPs. after stratifying to account for differences in MAF and LD across the genome. Most of the genetic variance was tagged by SNPs in the 1%-9% MAF range and in low LD with other SNPs in the region. Two markers in LOC I01927293 survived multiple-testing correction (i.e., q value< .05). Conclusions: Nearly half of the variation in opioid dependence can be attributed to common SNPs. Most of this variation is due to rare variants in low LD with other markers in the region.