- Charney, AW;
- Ruderfer, DM;
- Stahl, EA;
- Moran, JL;
- Chambert, K;
- Belliveau, RA;
- Forty, L;
- Gordon-Smith, K;
- Di Florio, A;
- Lee, PH;
- Bromet, EJ;
- Buckley, PF;
- Escamilla, MA;
- Fanous, AH;
- Fochtmann, LJ;
- Lehrer, DS;
- Malaspina, D;
- Marder, SR;
- Morley, CP;
- Nicolini, H;
- Perkins, DO;
- Rakofsky, JJ;
- Rapaport, MH;
- Medeiros, H;
- Sobell, JL;
- Green, EK;
- Backlund, L;
- Bergen, SE;
- Juréus, A;
- Schalling, M;
- Lichtenstein, P;
- Roussos, P;
- Knowles, JA;
- Jones, I;
- Jones, LA;
- Hultman, CM;
- Perlis, RH;
- Purcell, SM;
- McCarroll, SA;
- Pato, CN;
- Pato, MT;
- Craddock, N;
- Landén, M;
- Smoller, JW;
- Sklar, P
We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.