Abstract for presentation at 11th International Congress of Human Genetics

Haplotypes in a 750 kb fragment encoding SPEC2, PDZ-GEF2 and ACSL6 genes are associated with schizophrenia

  • Xiangning Chen, Virginia Commonwealth University, United States
  • Ms Xu Wang, Virginia Commonwealth University, United States
  • Ms Shaon Hossain, Virginia Commonwealth University, United States
  • Dr F O'Neil, The Queens University, Ireland
  • Dr Dermot Walsh, The Health Reseearch Board, Ireland
  • Dr Patrick Sullivan, University of North Carolina, United States
  • Dr Edwin van den Oord, Virginia Commonwealth University, United States
  • Dr Kenneth Kendler, Virginia Commonwealth University, United States

    • Chromosome 5q22-33 is a region where studies have repeatedly found evidence for linkage to schizophrenia. To identify the susceptibility genes in this region, we took a stepwise approach to systematically map the Irish study of high density schizophrenia families (ISHDSF) sample. In a screening subsample consisting of 61 families selected for evidence of linkage to this region, we genotyped 289 SNPs in an 8-million basepair interval defined by markers D5S2059 and D5S2053. We found that a 750 kb fragment, encoding for the SPEC2, PDZ-GEF2 and ACSL6 genes, showed consistent association with the disease. We followed up with this 750 kb interval by typing the remaining families of the ISHDSF sample (replication subsample) and an independent Irish case control sample for 24 SNPs. In the replication subsample (212 families), we observed multiple SNPs with p values ≤ 0.1. In haplotype analysis, significant associations were observed for both global and haplotype tests. For a 4-marker combination (markers13-14-15-16), using the broad disease definition, the global p was 0.00064 and the haplotype (1-2-1-2) p was 0.00016. The risk haplotypes identified in both the screening and replication subsamples were identical. In the case-control sample, only nominally significant genotypic associations were observed. A three-marker haplotype (markers 14-16-17) which overlaps with the core region from markers13-16 identified in the two family subsamples, reached global significance (p = 0.02918). From these data, we concluded that haplotypes underlying the SPEC2/PDZ-GEF2/ACSL6 region may be associated with schizophrenia. However, due to the extended high LD in this region, we were unable to distinguish whether the association signals came from one or more genes.

    Conference Organiser - ICMS Pty Ltd