Family-based association study of Epsin 4 and Schizophrenia

Abstract

Recently, Pimm et al. identified Epsin 4 on chromosome 5q33 as a susceptibility gene for schizophrenia in the British population, based on linkage and association evidence. In Pimm's case-control study, both the single polymorphisms and the individual haplotypes at the 5 0 end of the gene showed genetic association with schizophrenia. Here, we report the first study evaluating the relevance of Epsin 4 and schizophrenia outside the British population. Markers showing positive results in the original work as well as two additional polymorphisms were genotyped in 308 Han Chinese family trios. Transmission disequilibrium analysis was used to test for association of single-locus markers and multi-locus haplotypes with schizophrenia. Although no individual marker was significant at the P = 0.05 level, the haplotypes detected in our samples, different from those previously reported, showed strong evidence of association (most significant global P = 0.0021). Our results indicate the presence of a locus near the 5 0 end of Epsin 4 conferring susceptibility to the disease and provide further support for Epsin 4 as an important potential contributor to genetic risk in schizophrenia.

Segmental uniparental isodisomy on 5q32-qter in a patient with childhood-onset schizophrenia

“…18 Pimm et al 19 reported an association with the Epsin 4 gene found on 5q33.3, in a large case-control sample from the UK, and this gene was further implicated by a follow-up study on a Chinese sample that showed an association between Epsin 4 haplotypes and schizophrenia. 20 This gene is a schizophrenia candidate owing to its involvement with neurotransmitter vesicle transport and stability in the synapses and neurones. 19 Taken together, these studies provide strong evidence for schizophrenia susceptibility in the region in which we have confirmed an iUPD, a chromosomal abnormality that can be detrimental owing to the homozygosity of autosomal recessively inherited disorders and imprinting.…”

Genome-wide scan supports the existence of a susceptibility locus for schizophrenia and bipolar disorder on chromosome 15q26

“…In several of these loci association studies identified putative common susceptibility genes, such as DISC1 on chromosome 1q42, 13 FZD3 14 and NRG1 15 on 8p2, Epsin 4 17,18 and GABAA receptor 19 on chromosome 5q. In addition, a new gene, ST8SIA2 (also known as SIAT8B), which maps on chromosome 15q26, has been recently associated with SZ in a Japanese sample.…”

A narrow and highly significant linkage signal for severe bipolar disorder in the chromosome 5q33 region in Latin American pedigrees

“…ADAM19 , which is directly pinpointed by the presence of an exonic SNP significantly linked to BP‐I (rs1422795, LOD = 4.1), is an interesting functional candidate due to its role in the proteolytic processing of neuregulin 1 [Yokozeki et al, 2007], which is a key element of the neuregulin‐erbB signaling pathway, putatively impaired in psychiatric diseases [Roy et al, 2007]. The second candidate gene, CLINT1 , is suggested as a candidate for vulnerability to psychopathology by its association with schizophrenia in UK, Chinese, and Latin American populations [Pimm et al, 2005; Liou et al, 2006; Tang et al, 2006; Gurling et al, 2007; Escamilla et al, 2008]. Epsin 4 which is a protein product of the CLINT1 gene was shown to be involved in endocytotic internalization, regulation of inositol phospholipid levels, membrane structure, and trafficking through direct binding to membrane clathrin and other associated proteins, such as AP‐1 and AP‐2 [McPherson and Ritter, 2005].…”