Evidence for a chromosome 2p13–14 schizophrenia susceptibility locus in families from Palau, Micronesia

Abstract

A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning ෂ11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.

Genome-wide multipoint linkage analyses of multiplex schizophrenia pedigrees from the oceanic nation of Palau

“…This signal corresponds to that reported in Coon et al 25 for two point analysis. Again this signal reflects extensive haplotype-sharing, in this case more than half of the schizophrenics share a 25 cM haplotype.…”

“…Multipoint linkage analysis continued to lend some support to 2p, with LOD = 2.2 near D2S393 (80.2cM) under a dominant model. In the earlier analysis, 25 the maximum two-point LOD score (LOD = 2.17) occurred at D2S441, roughly 6 cM away from D2S393.…”

“…In an earlier report, Coon et al 25 identified two promising regions on the basis of two-point linkage analysis of K1583 under a dominant model, namely 2p and 1q. Our multipoint linkage analysis did not support the 1q finding: LOD scores were less than 0.3 everywhere on 1q.…”

“…From this unique population we also gathered extensive genealogical records. Previously 25 we reported genome-wide linkage results for one, large multiplex schizophrenia Palauan pedigree. Assuming autosomal dominant inheritance and a strict definition of illness, the highest two-point lod scores were found for loci mapping to 2p13-14, with a maximum lod score of 2.17 near D2S441.…”

Gene Expression of Metabolic Enzymes and a Protease Inhibitor in the Prefrontal Cortex Are Decreased in Schizophrenia

“…MDH1 is located at chromosome 2p13-14. Suggestive linkages in the region of 2p13-14 to schizophrenia (25,26) and to bipolar disorders (27) have been reported. A large meta-analysis of schizophrenia linkage studies showed one region to be highly significant (2p11.1-q21.1), which met the criterion for genome-wide significance (28).…”