Department of Psychiatry and Psychotherapy, Semmelweis University, 1083 Balassa u. 6., Budapest, Hungary.
Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 5;153B(3):792-801. doi: 10.1002/ajmg.b.31049.
Genetic association studies have yielded extensive but frequently inconclusive data about genetic risk factors for schizophrenia. Clinical and genetic heterogeneity are possible factors explaining the inconsistent findings. The objective of this study was to test the association of commonly incriminated candidate genes with two clinically divergent subgroups, non-deficit (SZ-ND) and deficit-schizophrenia (SZ-D), and symptom severity, in order to test for replication of previously reported results. A homogeneous sample of 280 schizophrenia patients and 230 healthy controls of Hungarian, Caucasian descent were genotyped for polymorphisms in schizophrenia candidate genes NRG1, DTNBP1, RGS4, G72/G30, and PIP5K2A. Patients were divided into the diagnostic subgroups of SZ-ND and SZ-D using the Schedule for Deficit Syndrome (SDS), and assessed clinically by the Positive and Negative Symptom Scale (PANSS). SNP8NRG241930 in NRG1 and rs1011313 in DTNBP1 were associated with SZ-ND (P = 0.04 and 0.03, respectively). Polymorphisms in RGS4, G72/G30, and PIP5K2A were neither associated with SZ-ND nor with SZ-D. SNP8NRG241930 showed association with the PANSS cognitive and hostility/excitability factors, rs1011313 with the negative factor and SDS total score, and rs10917670 in RGS4 was associated with the depression factor. Although these results replicate earlier findings about the genetic background of SZ-ND and SZ-D only partially, our data seem to confirm previously reported association of NRG1 with schizophrenia without prominent negative symptoms. It was possible to detect associations of small-to-medium effect size between the investigated candidate genes and symptom severity. Such studies have the potential to unravel the possible connection between genetic and clinical heterogeneity in schizophrenia.
遗传关联研究产生了广泛但经常不一致的关于精神分裂症遗传风险因素的数据。临床和遗传异质性可能是解释不一致发现的因素。本研究的目的是测试常见的可疑候选基因与两个临床上不同的亚组（非缺陷型精神分裂症[SZ-ND]和缺陷型精神分裂症[SZ-D]）以及症状严重程度之间的关联，以检验先前报道结果的复制情况。对来自匈牙利的 280 名精神分裂症患者和 230 名健康对照者的同质样本进行了精神分裂症候选基因 NRG1、DTNBP1、RGS4、G72/G30 和 PIP5K2A 多态性的基因分型。使用缺陷综合征量表（SDS）将患者分为 SZ-ND 和 SZ-D 诊断亚组，并使用阳性和阴性症状量表（PANSS）进行临床评估。NRG1 中的 SNP8NRG241930 和 DTNBP1 中的 rs1011313 与 SZ-ND 相关（P = 0.04 和 0.03）。RGS4、G72/G30 和 PIP5K2A 中的多态性既与 SZ-ND 也与 SZ-D 无关。SNP8NRG241930 与 PANSS 认知和敌意/兴奋因子相关，rs1011313 与阴性因子和 SDS 总分相关，RGS4 中的 rs10917670 与抑郁因子相关。尽管这些结果部分复制了关于 SZ-ND 和 SZ-D 遗传背景的早期发现，但我们的数据似乎证实了先前报道的 NRG1 与无明显阴性症状的精神分裂症之间的关联。可以检测到所研究的候选基因与症状严重程度之间的小到中等效应大小的关联。这些研究有可能揭示精神分裂症中遗传和临床异质性之间的可能联系。
