RT Journal Article
T1 Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.
A1 Jia, Xiaoming
A1 Goes, Fernando S
A1 Locke, Adam E
A1 Palmer, Duncan
A1 Wang, Weiqing
A1 Cohen-Woods, Sarah
A1 Genovese, Giulio
A1 Jackson, Anne U
A1 Jiang, Chen
A1 Kvale, Mark
A1 Mullins, Niamh
A1 Nguyen, Hoang
A1 Pirooznia, Mehdi
A1 Rivera, Margarita
A1 Ruderfer, Douglas M
A1 Shen, Ling
A1 Thai, Khanh
A1 Zawistowski, Matthew
A1 Zhuang, Yongwen
A1 Abecasis, Gonçalo
A1 Akil, Huda
A1 Bergen, Sarah
A1 Burmeister, Margit
A1 Chapman, Sinéad
A1 DelaBastide, Melissa
A1 Juréus, Anders
A1 Kang, Hyun Min
A1 Kwok, Pui-Yan
A1 Li, Jun Z
A1 Levy, Shawn E
A1 Monson, Eric T
A1 Moran, Jennifer
A1 Sobell, Janet
A1 Watson, Stanley
A1 Willour, Virginia
A1 Zöllner, Sebastian
A1 Adolfsson, Rolf
A1 Blackwood, Douglas
A1 Boehnke, Michael
A1 Breen, Gerome
A1 Corvin, Aiden
A1 Craddock, Nick
A1 DiFlorio, Arianna
A1 Hultman, Christina M
A1 Landen, Mikael
A1 Lewis, Cathryn
A1 McCarroll, Steven A
A1 Richard McCombie, W
A1 McGuffin, Peter
A1 McIntosh, Andrew
A1 McQuillin, Andrew
A1 Morris, Derek
A1 Myers, Richard M
A1 O'Donovan, Michael
A1 Ophoff, Roel
A1 Boks, Marco
A1 Kahn, Rene
A1 Ouwehand, Willem
A1 Owen, Michael
A1 Pato, Carlos
A1 Pato, Michele
A1 Posthuma, Danielle
A1 Potash, James B
A1 Reif, Andreas
A1 Sklar, Pamela
A1 Smoller, Jordan
A1 Sullivan, Patrick F
A1 Vincent, John
A1 Walters, James
A1 Neale, Benjamin
A1 Purcell, Shaun
A1 Risch, Neil
A1 Schaefer, Catherine
A1 Stahl, Eli A
A1 Zandi, Peter P
A1 Scott, Laura J
AB Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.
YR 2021
FD 2021-01-22
LK https://hdl.handle.net/10668/25662
UL https://hdl.handle.net/10668/25662
LA en
DS RISalud
RD Apr 17, 2025