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Title: Statistical genetic and genomic analysis of a large family with bipolar disorder
Author: Christoforou, Andrea Nikie
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Bipolar disorder (BP) and schizophrenia (SCZ) are severe and debilitating psychiatric illnesses, each affecting approximately one per cent of the population. Previously, several independent linkage studies identified chromosome 4p15-p16 as a putative region of susceptibility for BP and SCZ. The primary aim of our research group is to identify the gene(s) involved in these psychiatric illnesses, using multiple, integrative computational and experimental methods. First, I performed two association studies based on the chromosome 4p findings. Previous haplotype analysis of F22 and three other 4p-linked families had prioritised two sub-regions (B and D) of the linkage region, based on overlapping linkage evidence from the families. I completed a population-based association study of both BP and SCZ on a candidate gene, the G protein-coupled receptor 78 (GPR78), which lies within region B. Six tagging single nucleotide polymorphisms (SNPs) were tested and a female-specific association was observed with a SNP, located ~3kb upstream of GPR78, and its overlapping haplotypes (best P=0.003). I also completed the analysis of a larger association study, covering regions B and D with 408 SNPs selected from the International HapMap Project. My analysis identified 13 regions that were significant at the adjusted, region-specific significance levels (best P=3x10-6). These regions, and others meeting a more relaxed significance threshold, were selected for replication in an independent sample. Evidence for replication was observed for a number of these regions (best P=0.0004). Second, I initiated a genome-wide expression study, using lymphoblastoid cell lines from members of F22, with the aim of finding genes showing differential expression. I summarise the preliminary findings of the expression study, relating them to the 4p locus and other main candidate genes and pathways for psychiatric illness.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available