非裔美国人酒精依赖的全基因组密集连锁扫描：10号染色体上存在显著连锁。
Dense genomewide linkage scan for alcohol dependence in African Americans: significant linkage on chromosome 10.
作者信息
Gelernter Joel, Kranzler Henry R, Panhuysen Carolien, Weiss Roger D, Brady Kathleen, Poling James, Farrer Lindsay
机构信息
Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.
出版信息
Biol Psychiatry. 2009 Jan 15;65(2):111-5. doi: 10.1016/j.biopsych.2008.08.036. Epub 2008 Oct 18.
BACKGROUND
Alcohol dependence (AD) is costly to societies worldwide, moderately heritable, and genetically complex. Risk loci in several populations have been identified with genetic linkage analysis. To date, there has been no published linkage study of AD focused on African Americans (AAs).
METHODS
We completed a genomewide linkage scan with approximately 6000 single nucleotide polymorphism markers to map loci increasing risk for DSM-IV AD in a set of 238 small nuclear families ascertained on the basis of multiple individuals affected with cocaine or opioid dependence. Model free linkage analysis was completed with Merlin software. A modified marker set was used to avoid bias due to markers in strong linkage disequilibrium.
RESULTS
We identified a genomewide-significant linkage to markers near 117.2 centiMorgans on chromosome 10q23.3-24.1 (logarithm of odds score 3.32; p = 5.0E-05; empirical genomewide p = .033).
CONCLUSIONS
These data add to the growing evidence for locations for AD risk loci and provide the first linkage evidence for such a locus in the AA population.
背景
酒精依赖（AD）在全球范围内给社会带来高昂代价，具有中度遗传性且基因复杂。已通过遗传连锁分析在多个群体中确定了风险基因座。迄今为止，尚未有针对非裔美国人（AA）的酒精依赖连锁研究发表。
方法
我们使用约6000个单核苷酸多态性标记完成了全基因组连锁扫描，以在一组238个小核心家庭中绘制增加DSM-IV酒精依赖风险的基因座，这些家庭是基于多名受可卡因或阿片类药物依赖影响的个体确定的。使用Merlin软件完成无模型连锁分析。使用经过修改的标记集以避免因处于强连锁不平衡状态的标记而产生偏差。
结果
我们在10号染色体q23.3-24.1上117.2厘摩附近的标记处发现了全基因组显著连锁（优势对数得分3.32；p = 5.0E-05；经验性全基因组p = 0.033）。
结论
这些数据为酒精依赖风险基因座的位置提供了越来越多的证据，并为非裔美国人群体中此类基因座提供了首个连锁证据。
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