Stephens Sarah H, Franks Alexis, Berger Ralph, Palionyte Milda, Fingerlin Tasha E, Wagner Brandie, Logel Judith, Olincy Ann, Ross Randal G, Freedman Robert, Leonard Sherry
Department of Psychiatry, University of Colorado Denver, Colorado 80045, USA.
Psychiatr Genet. 2012 Feb;22(1):1-14. doi: 10.1097/YPG.0b013e32834c0c33.
The chromosomal region, 15q13-q14, including the α7 nicotinic acetylcholine receptor gene, CHRNA7, is a replicated region for schizophrenia. This study fine-mapped genes at 15q13-q14 to determine whether the association is unique to CHRNA7.
Family-based and case-control association studies were performed on Caucasian-non-Hispanic and African-American individuals from 120 families as well as 468 individual patients with schizophrenia and 144 well-characterized controls. Single-nucleotide polymorphism (SNP) markers were genotyped, and association analyses carried out for the outcomes of schizophrenia, smoking, and smoking in schizophrenia.
Three genes were associated with schizophrenia in both ethnic populations: TRPM1, KLF13, and RYR3. Two SNPs in CHRNA7 were associated with schizophrenia in African-Americans, and a second SNP in CHRNA7 was significant for an association with smoking and smoking in schizophrenia in Caucasians.
Results of these studies support association of the 15q13-q14 region with schizophrenia. The broad positive association suggests that more than one 15q gene may be contributing to the disorder, either in combination or through a regulatory mechanism.
包括α7烟碱型乙酰胆碱受体基因CHRNA7在内的染色体区域15q13 - q14是精神分裂症的一个重复区域。本研究对15q13 - q14区域的基因进行精细定位，以确定这种关联是否仅与CHRNA7有关。
对来自120个家庭的非西班牙裔白人和非裔美国人个体以及468例精神分裂症患者个体和144例特征明确的对照进行基于家系和病例对照的关联研究。对单核苷酸多态性（SNP）标记进行基因分型，并对精神分裂症、吸烟以及精神分裂症患者吸烟情况进行关联分析。
在两个种族群体中，有三个基因与精神分裂症相关：瞬时受体电位阳离子通道亚家族M成员1（TRPM1）、 Kruppel样因子13（KLF13）和兰尼碱受体3（RYR3）。CHRNA7中的两个SNP与非裔美国人的精神分裂症相关，CHRNA7中的另一个SNP在白种人中与吸烟以及精神分裂症患者吸烟显著相关。
这些研究结果支持15q13 - q14区域与精神分裂症的关联。广泛的阳性关联表明，15q上可能有不止一个基因对该疾病有影响，可能是联合作用或通过调节机制起作用。
