Abstract
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.
DOI
10.1038/tp.2016.242
Publication Date
2017-01-10
Publication Title
Translational Psychiatry
Volume
7
Issue
1
Publisher
Springer Science and Business Media LLC
ISSN
2158-3188
Embargo Period
2024-11-19
First Page
e993
Last Page
e993
Recommended Citation
Charney, A., Ruderfer, D., Stahl, E., & et al. (2017) 'Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder', Translational Psychiatry, 7(1), pp. e993-e993. Springer Science and Business Media LLC: Available at: https://doi.org/10.1038/tp.2016.242