@misc{10481/103453,
year = {2025},
month = {1},
url = {https://hdl.handle.net/10481/103453},
abstract = {Bipolar disorder (BD) is a leading contributor to the global burden of disease 1 . Despite high
heritability (60-80%), the majority of the underlying genetic determinants remain unknown 2 . We
analysed data from participants of European, East Asian, African American and Latino
ancestries (n=158,036 BD cases, 2.8 million controls), combining Clinical, Community, and Self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-
analysis, a 4-fold increase over previous findings 3 , and identified a novel ancestry-specific
association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of BD. Genes prioritised
through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating
variations in BD cases 4 , highlighting convergence of common and rare variant signals. We
report differences in genetic architecture of BD depending on the source of patient
ascertainment and on BD-subtype (BDI and BDII). Several analyses implicate specific cell types
in BD pathophysiology, including GABAergic interneurons and medium spiny neurons.
Together, these analyses provide novel insights into the genetic architecture and biological
underpinnings of BD.},
organization = {US National Institute of Mental Health (PGC4: R01 MH124839, PGC3: U01 MH109528, PGC2: U01 MH094421, PGC1: U01 MH085520)},
publisher = {Springer Nature},
title = {Genomics yields biological and phenotypic insights into bipolar disorder},
doi = {10.1038/s41586-024-08468-9},
doi = {10.1101/2023.10.07.23296687},
author = {O’Connell, Kevin S. and Rivera Sánchez, Margarita and Bipolar Disorder Working Group},
}