期刊
BIOLOGICAL PSYCHIATRY
卷 72, 期 8, 页码 645-650出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2012.02.040
关键词
3p21.1; bipolar disorder; genetics; polybromo 1; genome-wide association; schizophrenia
资金
- European Union [LSHM-CT-2006-037761]
- National Alliance for Research in Schizophrenia and Affective Disorders
- State Scholarship Foundation of Greece
- Romanian Ministry for Education and Research [CNMP/UEFISCDI-42-151/2008]
- National Institute of Mental Health [R01 MH078075]
- Oslo University Hospital-Ulleval
- Eastern Norway Health Authority [2004-123]
- Research Council of Norway [167153/V50, 163070/V50, 183782/V50]
- Danish Strategic Research Council
- Astra-Zeneca Belgium
- German Federal Ministry of Education and Research (BMBF)
- National Genome Research Network plus (NGFNplus)
- Integrated Genome Research Network (IG) MooDS [01GS08144, 01GS08147]
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 x 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.
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