Yu Yi, Kranzler Henry R, Panhuysen Carolien, Weiss Roger D, Poling James, Farrer Lindsay A, Gelernter Joel
Department of Medicine (Genetics Program), Boston University Schools of Medicine and Public Health, Boston, MA, USA.
Hum Genet. 2008 Jun;123(5):495-506. doi: 10.1007/s00439-008-0501-0. Epub 2008 Apr 26.
Cocaine and opioid dependence are common, complex disorders with high heritability that commonly co-occur with other substance dependence disorders. Improved insight into the genetic basis of substance dependence would help elucidate its etiology and could inform its prevention and treatment. To generate new hypotheses about the genetics of substance dependence, we genotyped 5633 tagging single nucleotide polymorphism (SNP) markers in 1699 subjects from 339 African American (AA) families and 334 European American (EA) families ascertained through a sib pair meeting DSM-IV criteria for either cocaine or opioid dependence. The associations between genetic markers and five substance dependence traits (cocaine dependence, opioid dependence, cocaine-induced paranoia, alcohol dependence, and nicotine dependence) were assessed by family based association tests (FBAT). Results were ranked according to several criteria including statistical significance, concordance of results across population samples, and potential biological relevance of the implicated gene. The top-ranked result was an association of SNP rs1133503 in the MANEA gene with cocaine-induced paranoia (CIP). Our study provides an initial substance dependence trait-specific blueprint of associated regions for future candidate gene studies.
可卡因和阿片类药物依赖是常见的、复杂的且具有高遗传性的疾病，通常与其他物质依赖障碍同时出现。对物质依赖的遗传基础有更深入的了解将有助于阐明其病因，并可为其预防和治疗提供依据。为了生成关于物质依赖遗传学的新假设，我们对来自339个非裔美国家庭和334个欧裔美国家庭的1699名受试者中的5633个标签单核苷酸多态性（SNP）标记进行了基因分型，这些家庭是通过同胞对符合DSM-IV可卡因或阿片类药物依赖标准来确定的。通过基于家系的关联测试（FBAT）评估遗传标记与五种物质依赖性状（可卡因依赖、阿片类药物依赖、可卡因诱发的偏执狂、酒精依赖和尼古丁依赖）之间的关联。根据包括统计学显著性、不同人群样本结果的一致性以及所涉及基因的潜在生物学相关性等几个标准对结果进行排名。排名最高的结果是MANEA基因中的SNP rs1133503与可卡因诱发的偏执狂（CIP）之间的关联。我们的研究为未来的候选基因研究提供了一个初步的物质依赖性状特异性相关区域蓝图。
