期刊
BIOLOGICAL PSYCHIATRY
卷 75, 期 5, 页码 386-397出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2013.03.033
关键词
Bipolar disorder; genome-wide association; meta-analysis; polygenic score analysis; psychosis; schizophrenia
资金
- Wellcome Trust, as part of the Wellcome Trust Case Control Consortium 2 project [085475/B/08/Z, 085475/Z/08/Z]
- MRC New Investigator Award
- MRC Centenary Award
- National Institute of Health Research UK
- Psychiatry Research Trust
- Schizophrenia Research Fund
- Brain and Behavior Research foundation's (NARSAD's) Young Investigator Award
- Wellcome Trust Research Training Fellowship
- NIHR Biomedical Research Centre for Mental Health at the South London
- Maudsley NHS Foundation Trust
- Institute of Psychiatry Kings College London
- Royal Society Wolfson Merit Award
- Wellcome Trust Fellowship [097364/Z/11/Z]
- Academy of Finland [257654]
- Medical Research Council [G0000934]
- Wellcome Trust [068545/Z/02]
- UK National Blood Service controls
- Wellcome Trust
- People of the British Isles collection
- Wellcome Trust Centre for Human Genetics core grants [072894/Z/03/Z, 090532/Z/09/Z, 075491/Z/04/B]
- Wellcome Trust Research Training Fellowship [064971]
- NARSAD independent investigator award
- Health Foundation Clinician Scientist Award
- Wellcome Trust Clinical Research Training Fellowship
- Royal Society Dorothy Hodgkin Fellowship
- Geestkracht programme of the Dutch Health Research Council [10-000-1002]
- EU Seventh Framework Programme [HEALTH-F2-2009-241909]
- German Research Community (Deutsche Forschungsgemeinschaft, DFG) [WE-1996/ 1-3]
- NIMH grant [1R01MH078075]
- National Health and Medical Research Council, Australia [513874]
- North Metropolitan Health Service, Perth, Australia
- Instituto de Salud Carlos III [PI020499, PI050427, PI060507]
- SENY Fundacic [CI 20050308007]
- Fundacion Ramon Areces
- Fundacion Marques de Valdecilla [API07/011, API10/13]
- Medical Research Council [G0901310, G9817803B, G1100583, G0000934] Funding Source: researchfish
- National Institute for Health Research [PDA/02/06/016] Funding Source: researchfish
- MRC [G1100583, G0901310, G0000934] Funding Source: UKRI
- Wellcome Trust [097364/Z/11/Z] Funding Source: Wellcome Trust
Background: Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories. Methods: 1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls). Results: No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p.003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 x 10(-14)) and explained approximately 2% of the phenotypic variance. Conclusions: Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through metaanalysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data.
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