Chen Y-S, Akula N, Detera-Wadleigh S D, Schulze T G, Thomas J, Potash J B, DePaulo J R, McInnis M G, Cox N J, McMahon F J
Department of Human Genetics, The University of Chicago, Chicago, IL, USA.
Mol Psychiatry. 2004 Jan;9(1):87-92; image 5. doi: 10.1038/sj.mp.4001453.
Markers near the nested genes G72 and G30 on chromosome 13q33 have been implicated in the etiology of schizophrenia and, recently, bipolar affective disorder (BPAD). Hattori et al (2003) reported that single-nucleotide polymorphisms (SNPs) near the G72/G30 locus were associated with BPAD in a sample of 22 pedigrees, and that SNP haplotypes were associated in a second, larger sample of triads. The present study attempts to replicate this finding in an independent case-control sample. Six SNPs near the G72/G30 locus, including the most strongly associated markers in the previous study, were tested in 139 cases and 113 ethnically matched controls. Significant association was detected between BPAD and two adjacent SNPs (smallest P=0.007; global P=0.024). Haplotype analysis produced additional support for association (smallest P=0.004; global P=0.004). Analysis of 31 unlinked microsatellite markers detected no population stratification in the cases or controls studied. Although the associated alleles and haplotypes differ from those previously reported, these new results provide further evidence, in an independent sample, for an association between BPAD and genetic variation in the vicinity of the genes G72 and G30.
位于13号染色体q33区域的嵌套基因G72和G30附近的标记物已被证实与精神分裂症的病因有关，最近又发现与双相情感障碍（BPAD）有关。Hattori等人（2003年）报告称，在一个包含22个家系的样本中，G72/G30基因座附近的单核苷酸多态性（SNP）与BPAD有关，并且在另一个更大的三联体样本中，SNP单倍型也存在关联。本研究试图在一个独立的病例对照样本中重复这一发现。在139例病例和113例种族匹配的对照中，对G72/G30基因座附近的6个SNP进行了检测，其中包括先前研究中关联性最强的标记物。在BPAD与两个相邻的SNP之间检测到显著关联（最小P值 = 0.007；整体P值 = 0.024）。单倍型分析为这种关联性提供了更多支持（最小P值 = 0.004；整体P值 = 0.004）。对31个不连锁的微卫星标记物进行分析，在所研究的病例或对照中未检测到群体分层现象。尽管相关的等位基因和单倍型与先前报道的不同，但这些新结果在一个独立样本中进一步证明了BPAD与G72和G30基因附近的遗传变异之间存在关联。
