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Background
Co
mmon genetic poly
morphis
ms at chro
moso
me 3p21.1, including rs2251219 in
m>polybromo 1m> (
m>PBRM1m>), have been i
mplicated in susceptibility to bipolar affective disorder (BP) through geno
me-wide association studies. Subsequent studies have suggested that this is also a risk locus for other psychiatric phenotypes, including
major depression and schizophrenia.
Methods
To replicate the association, we studied 2562 cases with BP and 25,439 control subjects collected from seven cohorts with either genome-wide association or individual genotyping of rs2251219 and tagging single nucleotide polymorphisms across the m>PBRM1m> gene. Results from the different case-control groups were combined with the inverse variance weighting method.
Results
In our dataset, rs2251219 was associated with BP (odds ratio [OR] = .89, m>pm> = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, m>pm> = 2.68 ¡Á 10?9). Genotypic data from the SGENE-plus consortium were used to examine the association of the same variant with schizophrenia in an overall sample of 8794 cases and 25,457 control subjects, but this was not statistically significant (OR = .97, m>pm> = .21).
Conclusions
There is strong evidence of association of rs2251219 with BP. However, our data do not support association of this marker with schizophrenia. Because the region of association has high linkage disequilibrium, forming a large haplotype block across many genes, it is not clear which gene is causally implicated in the disorder.