Genome-Wide Scan in 124 Indonesian Sib-Pair Families With Schizophrenia Reveals Genome-Wide Significant Linkage to a Locus on Chromosome 3p26-21

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 genomewide significant linkage, which will serve as starting point for identification of schizophrenia susceptibility genes in the Indonesian population. (C) 2008 Wiley-Liss, Inc.