Genomic dissection of bipolar disorder and schizophrenia including 28 subphenotypes

Abstract

Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable disorders that share a significant proportion of common risk variation. Understanding the genetic factors underlying the specific symptoms of these disorders will be crucial for improving diagnosis, intervention and treatment. In case-control data consisting of 53,555 cases (20,129 BD,33,426 SCZ) and 54,065 controls, we identified 114 genome-wide significant loci (GWS) when comparing all cases to controls, of which 41 represented novel findings. Two genome-wide significant loci were identified when comparing SCZ to BD and a third was found when directly incorporating functional information. Regional joint association identified a genomic region of overlapping association in BD and SCZ with disease-independent causal variants indicating a fourth region contributing to differences between these disorders. Regional SNP-heritability analyses demonstrated that the estimated heritability of BD based on the SCZ GWS regions was significantly higher than that based on the average genomic region (91 regions, p = 1. have identified specific loci pointing to a potential role of 4 genes (DARS2, ARFGEF2, DCAKD and GATAD2A) that distinguish between BD and SCZ, providing an opportunity to understand . CC-BY-NC-ND 4.0 International license It is made available under a was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/173435 doi: bioRxiv preprint first posted online Aug. 8, 2017; the biology contributing to clinical differences of these disorders. Our results provide the best evidence so far of genomic components distinguishing between BD and SCZ that contribute directly to specific symptom dimensions.

Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

“…Mental disorders are generally associated with phenotypic impairments in academic achievement and social role functioning, 52,53 but positive genetic correlations with educational attainment and creativity have been reported for some disorders 54,55 . We therefore tested NonCog rg with psychiatric disorders based on published case-control GWAS [56][57][58][59][60][61][62] In sum NonCog genetics were associated with phenotypes from economics and psychology thought to mediate non-cognitive influences on educational success. These associations contrasted with associations for Cog genetics, supporting distinct pathways of influence on achievement in school and later in life.…”

Genetic correlates of evolutionary adaptations in cognitive functional brain networks and their relationship to human cognitive functioning and disease

“…We used the SNP-based association statistics of a GWAS in 33,426 schizophrenia patients and 54,065 healthy controls 31 provided by the Psychiatric Genomics Consortium (http://www.med.unc.edu/pgc/). Using gene-set analysis, we observed HAR/HAR-BRAIN genes to be significantly associated with genetic variants in schizophrenia (ß = 0.056, p = 1.78 × 10 -11 for HAR genes; ß = 0.076, p = 1.82 × 10 -19 for HAR-BRAIN genes; Supplementary Table 8).…”

Gene-Set Enrichment with Mathematical Biology

“…Summary genetic data was obtained on subjects with bipolar disorder (n=20,129) and controls (n=21,524) from the Psychiatric Genomics Consortium (PGC) [53,54]. Association was measured between 8,958,989 SNPs and bipolar disorder, resulting in P-values for each SNP.…”