Zuo Lingjun, Luo Xingguang, Listman Jennifer B, Kranzler Henry R, Wang Shuang, Anton Raymond F, Blumberg Hilary P, Stein Murray B, Pearlson Godfrey D, Covault Jonathan, Charney Dennis S, van Kammen Daniel P, Price Lawrence H, Lappalainen Jaakko, Cramer Joyce, Krystal John H, Gelernter Joel
Department of Psychiatry, Yale University School of Medicine, VA Psychiatry 116A2, West Haven, CT 06516, USA.
Hum Genet. 2009 Jun;125(5-6):605-13. doi: 10.1007/s00439-009-0647-4. Epub 2009 Mar 22.
The admixture of different ancestral populations in America may have important implications for the risk for psychiatric disorders, as it appears to have for other medical disorders. The present study investigated the role of population admixture in risk for several psychiatric disorders in European-Americans (EAs) and African-Americans (AAs). This is a multisite study with 3,792 subjects recruited from across the United States, including 3,119 EAs and 673 AAs. These subjects included healthy controls and those with substance dependence (SD) [including alcohol dependence (AD), cocaine dependence, and opioid dependence], social phobia, affective disorders, and schizophrenia. In addition, DNA was included from 78 West Africans. The degree of admixture for each subject was estimated by analysis of a set of ancestry-informative genetic markers using the program STRUCTURE, and was compared between cases and controls. As noted previously, the degree of admixture in AAs was higher than EAs. In EAs, the degree of admixture (with African ancestry) was significantly lower in patients with SD (mainly AD) than controls (P = 0.009 for SD; P = 0.008 for AD). This finding suggests that population admixture may modulate risk for alcohol dependence. Population admixture might protect against alcohol dependence by increasing average heterozygosity and reducing the risk of deleterious recessive alleles. We cannot exclude the possibility that the results might have been influenced by selection bias due to the multisite nature of the study.
在美国，不同祖先群体的混合可能对精神疾病的风险具有重要影响，就如同其对其他医学疾病的影响一样。本研究调查了群体混合在欧洲裔美国人（EAs）和非裔美国人（AAs）患几种精神疾病风险中的作用。这是一项多中心研究，从美国各地招募了3792名受试者，其中包括3119名EAs和673名AAs。这些受试者包括健康对照者以及患有物质依赖（SD）[包括酒精依赖（AD）、可卡因依赖和阿片类药物依赖]、社交恐惧症、情感障碍和精神分裂症的患者。此外，还纳入了78名西非人的DNA。使用STRUCTURE程序通过分析一组祖先信息遗传标记来估计每个受试者的混合程度，并对病例组和对照组进行比较。如前所述，AAs的混合程度高于EAs。在EAs中，患有SD（主要是AD）的患者的（非洲血统）混合程度显著低于对照组（SD的P = 0.009；AD的P = 0.008）。这一发现表明群体混合可能调节酒精依赖的风险。群体混合可能通过增加平均杂合性和降低有害隐性等位基因的风险来预防酒精依赖。由于该研究的多中心性质，我们不能排除结果可能受到选择偏倚影响的可能性。
