1. Replication study and meta-analysis in European samples supports association of the 3p21.1 locus with bipolar disorder.
- Author
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Vassos E, Steinberg S, Cichon S, Breen G, Sigurdsson E, Andreassen OA, Djurovic S, Morken G, Grigoroiu-Serbanescu M, Diaconu CC, Czerski PM, Hauser J, Babadjanova G, Abramova LI, Mühleisen TW, Nöthen MM, Rietschel M, McGuffin P, St Clair D, Gustafsson O, Melle I, Pietiläinen OP, Ruggeri M, Tosato S, Werge T, Ophoff RA, Rujescu D, Børglum AD, Mors O, Mortensen PB, Demontis D, Hollegaard MV, van Winkel R, Kenis G, De Hert M, Réthelyi JM, Bitter I, Rubino IA, Golimbet V, Kiemeney LA, van den Berg LH, Franke B, Jönsson EG, Farmer A, Stefansson H, Stefansson K, and Collier DA
- Subjects
- Databases, Genetic statistics & numerical data, Europe epidemiology, Female, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Odds Ratio, Schizophrenia genetics, White People genetics, Bipolar Disorder genetics, Chromosomes, Human, Pair 3 genetics, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics
- Abstract
Background: Common genetic polymorphisms at chromosome 3p21.1, including rs2251219 in polybromo 1 (PBRM1), have been implicated in susceptibility to bipolar affective disorder (BP) through genome-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 PBRM1 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, p = .003), and meta-analysis of previously published data with our nonoverlapping new data confirmed genome-wide significant association (OR = .875, p = 2.68 × 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, p = .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., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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