Schwab S G, Handoko H Y, Kusumawardhani A, Widyawati I, Amir N, Nasrun M W S, Holmans P, Knapp M, Wildenauer D B
Department of Psychiatry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.
Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1245-52. doi: 10.1002/ajmg.b.30763.
Variation in incidence of schizophrenia between populations with different ethnical background may reflect population specific differences in nature and composition of genetic and environmental factors. In order to investigate whether there are population specific susceptibility genes for schizophrenia, we collected in Indonesia families with two or more affected siblings and, as far as available, parents and unaffected siblings, suitable for genetic linkage- and association studies. After checking extensively for incompatibilities with Mendelian inheritance as well as for errors in sampling, we used 124 families from the sample of 152 originally ascertained families for linkage analysis. Genotyping was performed at the NHLBI Mammalian Genotyping Service at Marshfield Research Organisation using the Screening Set 16, which comprises 402 Short Tandem Repeat Polymorphisms (STRPs). The genotypes of 540 individuals including 267 affected with schizophrenia were used for analysis. Multipoint sib-pair linkage analysis was carried out by estimation of--allele sharing derived--maximum likelihood LOD scores (MLS) in 154 sib-pair combinations. We obtained a genome-wide significant MLS of 3.76 on chromosome 3p26.2-25.3. Genome-wide significance was estimated by performing 10,000 simulated genomescans. Additional loci were detected on 1p12, which produced suggestive evidence for linkage (MLS = 2.35), as well as on 5q14.1 (MLS = 1.56), 5q33.3 (MLS = 1.11), and 10q (MLS = 1.17), where linkage had been reported previously. In conclusion, our study detected a region with genome-wide significant linkage, which will serve as starting point for identification of schizophrenia susceptibility genes in the Indonesian population.
具有不同种族背景的人群中精神分裂症发病率的差异可能反映了遗传和环境因素的性质及构成在人群中的特异性差异。为了研究精神分裂症是否存在人群特异性易感基因，我们在印度尼西亚收集了有两个或更多患病同胞的家庭，以及尽可能获取的父母和未患病同胞，这些家庭适合进行遗传连锁和关联研究。在广泛检查与孟德尔遗传的不相容性以及抽样误差后，我们从最初确定的152个家庭样本中选取了12个家庭进行连锁分析。基因分型在马什菲尔德研究组织的美国国立心肺血液研究所哺乳动物基因分型服务中心进行，使用包含402个短串联重复多态性（STRP）的筛选集16。对包括267名精神分裂症患者在内的540名个体的基因型进行了分析。通过估计等位基因共享衍生的最大似然LOD分数（MLS），对154个同胞对组合进行了多点同胞对连锁分析。我们在3号染色体p26.2 - 25.3区域获得了全基因组显著的MLS为3.76。通过进行10000次模拟全基因组扫描估计全基因组显著性。在1p12上检测到其他位点，产生了连锁的提示性证据（MLS = 2.35），以及在5q14.1（MLS = 1.56）、5q33.3（MLS = 1.11）和10q（MLS = 1.17）上，这些区域之前已有连锁报道。总之，我们的研究检测到一个具有全基因组显著连锁的区域，这将作为在印度尼西亚人群中鉴定精神分裂症易感基因的起点。
