Genetic utility of broadly defined bipolar schizoaffective disorder as a diagnostic concept.
paper
Cited
Public
- Authors
- Hamshere, M L; Green, E K; Jones, I R; Jones, L; Moskvina, V; Kirov, G; Grozeva, D; Nikolov, I; Vukcevic, D; Caesar, S; Gordon-Smith, K; Fraser, C; Russell, E; Breen, G; St Clair, D; Collier, D A; Young, A H; Ferrier, I N; Farmer, A; McGuffin, P; Wellcome Trust Case Control Consortium; Holmans, P A; Owen, M J; O'Donovan, M C; Craddock, N
- Year
- 2009
- Journal
- The British journal of psychiatry : the journal of mental science
- PMID
- 19567891
- DOI
- 10.1192/bjp.bp.108.061424
- PMCID
- PMC2802523
BACKGROUND: Psychiatric phenotypes are currently defined according to sets of descriptive criteria. Although many of these phenotypes are heritable, it would be useful to know whether any of the various diagnostic categories in current use identify cases that are particularly helpful for biological-genetic research. AIMS: To use genome-wide genetic association data to explore the relative genetic utility of seven different descriptive operational diagnostic categories relevant to bipolar illness within a large UK case-control bipolar disorder sample. METHOD: We analysed our previously published Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder genome-wide association data-set, comprising 1868 individuals with bipolar disorder and 2938 controls genotyped for 276 122 single nucleotide polymorphisms (SNPs) that met stringent criteria for genotype quality. For each SNP we performed a test of association (bipolar disorder group v. control group) and used the number of associated independent SNPs statistically significant at P<0.00001 as a metric for the overall genetic signal in the sample. We next compared this metric with that obtained using each of seven diagnostic subsets of the group with bipolar disorder: Research Diagnostic Criteria (RDC): bipolar I disorder; manic disorder; bipolar II disorder; schizoaffective disorder, bipolar type; DSM-IV: bipolar I disorder; bipolar II disorder; schizoaffective disorder, bipolar type. RESULTS: The RDC schizoaffective disorder, bipolar type (v. controls) stood out from the other diagnostic subsets as having a significant excess of independent association signals (P<0.003) compared with that expected in samples of the same size selected randomly from the total bipolar disorder group data-set. The strongest association in this subset of participants with bipolar disorder was at rs4818065 (P = 2.42 x 10(-7)). Biological systems implicated included gamma amniobutyric acid (GABA)(A) receptors. Genes having at least one associated polymorphism at P<10(-4) included B3GALTS, A2BP1, GABRB1, AUTS2, BSN, PTPRG, GIRK2 and CDH12. CONCLUSIONS: Our findings show that individuals with broadly defined bipolar schizoaffective features have either a particularly strong genetic contribution or that, as a group, are genetically more homogeneous than the other phenotypes tested. The results point to the importance of using diagnostic approaches that recognise this group of individuals. Our approach can be applied to similar data-sets for other psychiatric and non-psychiatric phenotypes.
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| Name | Type |
|---|---|
| 2938 controls local | cohort |
| A2BP1 | gene |
| ABHD2 local | gene |
| associations local | phenotype |
| ataxin-2 local | drug |
| ataxin 2-binding protein 1 isoform 4 local | drug |
| autism | phenotype |
| AUTS2 | gene |
| B3GALT5 local | gene |
| bipolar disorder | phenotype |
| Bipolar disorder cohort local | cohort |
| bipolar disorder data-set local | cohort |
| bipolar disorder not otherwise specified local | phenotype |
| bipolar disorder set local | cohort |
| Bipolar disorder spectrum local | phenotype |
| bipolar I disorder | phenotype |
| bipolar II disorder | phenotype |
| bipolar phenotype local | phenotype |
| Bipolar-spectrum diagnostic subsets local | phenotype |
| Bipolar type local | phenotype |
| BSN local | gene |
| C13orf30 local | gene |
| case sample size local | cohort |
| CDH12 | gene |
| chromosome 16p13.3 local | anatomy |
| chromosome 21 local | anatomy |
| clinical phenotypes | phenotype |
| common variants | cohort |
| control | cohort |
| controls | cohort |
| diagnostic phenotype definition local | phenotype |
| diagnostic phenotype definitions local | phenotype |
| DSMβIV | phenotype |
| DSM-IV bipolar I disorder local | cohort |
| DSM-IV bipolar II disorder local | cohort |
| DSMβIV definition of schizoaffective disorder, bipolar type local | phenotype |
| DSM-IV schizoaffective disorder, bipolar type local | cohort |
| DSMβIV schizoaffective disorder, bipolar type local | phenotype |
| DSMβV local | cohort |
| epilepsy | phenotype |
| European population | cohort |
| FLJ18221 local | gene |
| Full bipolar disorder sample local | cohort |
| GABAA receptor | drug |
| Gabra4 | gene |
| GABRA5 | gene |
| GABRB1 | gene |
| Gabrb3 | gene |
| GABRR1 | gene |
| genetic risk | cohort |
| genetic variants | cohort |
| genome-wide association study data local | cohort |
| GRIK2 | gene |
| ICDβ11 local | cohort |
| LPIN1 local | gene |
| major psychiatric illness | phenotype |
| manic disorder local | phenotype |
| mental retardation | phenotype |
| Moodβpsychosis disorders local | phenotype |
| participants with bipolar disorder who had experienced psychotic symptoms local | cohort |
| PRSS35 local | gene |
| psychiatric disorders | phenotype |
| psychosis | phenotype |
| PTPRG local | gene |
| rare variant | cohort |
| RDC local | phenotype |
| RDC bipolar I disorder local | cohort |
| RDC bipolar II disorder local | cohort |
| RDC dataset local | cohort |
| RDC definition of schizoaffective disorder, bipolar type local | phenotype |
| RDC diagnostic sets local | cohort |
| RDC manic disorder local | cohort |
| RDC schizoaffective bipolar cohort local | cohort |
| RDC schizoaffective disorder local | phenotype |
| RDC schizoaffective disorder, bipolar type local | cohort |
| RDC schizoaffective disorder, bipolar type local | phenotype |
| RDC schizoaffective disorder, bipolar type data-set local | cohort |
| RDC schizoaffective disorder, bipolar type diagnostic set local | cohort |
| RDC schizoaffective disorder, bipolar type group local | cohort |
| RDC schizoaffective disorder, bipolar type sample local | cohort |
| RDC schizoaffective disorder, bipolar type subset local | cohort |
| RDC schizoaffective disorder, depressed type local | phenotype |
| Research Diagnostic Criteria (RDC) schizoaffective disorder, bipolar type group local | cohort |
| rs1171115 local | variant |
| rs13154602 local | variant |
| rs16942644 local | variant |
| rs2352974 local | variant |
| rs4027132 local | variant |
| rs4279178 local | variant |
| rs4786811 local | variant |
| rs4818065 local | variant |
| rs7680321 local | variant |
| rs7990962 local | variant |
| schizoaffective disorder | phenotype |
| schizoaffective disorder, bipolar type local | phenotype |
| Schizoaffective disorder, bipolar type local | phenotype |
| schizoaffective illness local | phenotype |
| schizophrenia | phenotype |
| schizophrenia data-set local | cohort |
| schizophrenia spectrum local | phenotype |
| SNP | cohort |
| spinocerebellar ataxia type 2 local | phenotype |
| structural variant | cohort |
| Subset of participants with bipolar disorder local | cohort |
| Subset under investigation local | cohort |
| total bipolar disorder set local | cohort |
| TRAIP local | gene |
| twin and family samples local | cohort |
| UK 1958 birth cohort local | cohort |
| UK Blood Donor Service local | cohort |
| WTCCC | cohort |
| WTCCC bipolar disorder cohort local | cohort |
| WTCCC bipolar disorder data-set local | cohort |
| WTCCC bipolar disorder GWAS dataset local | cohort |
| WTCCC control cohort local | cohort |
| WTCCC participants local | cohort |
| WTCCC study of bipolar disorder local | cohort |
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