Dick Danielle M, Aliev Fazil, Kramer John, Wang Jen C, Hinrichs Anthony, Bertelsen Sarah, Kuperman Sam, Schuckit Marc, Nurnberger John, Edenberg Howard J, Porjesz Bernice, Begleiter Henri, Hesselbrock Victor, Goate Alison, Bierut Laura
Department of Psychiatry, Washington University in St. Louis, 660 South Euclid Ave., Box 8134, St. Louis, MO 63130, USA.
Behav Genet. 2007 Mar;37(2):265-72. doi: 10.1007/s10519-006-9131-2. Epub 2006 Dec 12.
The cholinergic neurotransmitter system is thought to be involved in many aspects of memory, attention, and higher cognition. In the Collaborative Study on the Genetics of Alcoholism (COGA) sample, we have previously reported linkage and association to the cholinergic muscarinic 2 receptor gene (CHRM2) on chromosome 7 with evoked EEG oscillations (Jones et al. 2004), providing evidence that this gene may be involved in human brain dynamics and cognition. In addition, a small number of genetic markers were genotyped in CHRM2 in the Minnesota Twin and Family Study (Comings et al. 2003) and a Dutch family study (Gosso et al. 2006, in press) and both research groups found evidence that this gene may be involved in intelligence. In the COGA sample, we have extensively genotyped SNPs within and flanking the CHRM2 gene. We find evidence of association with multiple SNPs across CHRM2 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R). These results remain significant after taking into account alcohol dependence and depression diagnoses in the sample.
胆碱能神经递质系统被认为与记忆、注意力及高级认知的诸多方面有关。在酒精中毒遗传学合作研究(COGA)样本中,我们之前曾报告过7号染色体上的胆碱能毒蕈碱2受体基因(CHRM2)与诱发脑电图振荡存在连锁和关联(琼斯等人,2004年),这为该基因可能参与人类脑动力学和认知提供了证据。此外,在明尼苏达双胞胎与家庭研究(科明斯等人,2003年)以及一项荷兰家庭研究(戈索等人,2006年,即将发表)中,对CHRM2中的少量遗传标记进行了基因分型,两个研究小组均发现有证据表明该基因可能与智力有关。在COGA样本中,我们对CHRM2基因内部及侧翼的单核苷酸多态性(SNP)进行了广泛的基因分型。我们发现,通过韦氏成人智力量表修订版(WAIS-R)测量,CHRM2基因上多个SNP与操作智商之间存在关联证据。在考虑样本中的酒精依赖和抑郁症诊断情况后,这些结果仍然显著。