Functional classes of SNPs related to psychiatric disorders and behavioral traits contrast with those related to neurological disorders

Abstract

We investigated the functional classes of genomic regions containing SNPS contributing most to the SNP-heritability of important psychiatric and neurological disorders and behavioral traits, as determined from recent genome-wide association studies. We employed linkage-disequilibrium score regression with several brain-specific genomic annotations not previously used. The classes of genomic annotations conferring substantial SNP-heritability for the psychiatric disorders and behavioral traits differed systematically from the classes associated with neurological disorders, and both differed from the classes enriched for height, a biometric trait used here as a control outgroup. The SNPs implicated in these psychiatric disorders and behavioral traits were highly enriched in CTCF binding sites, in conserved regions likely to be enhancers, and in brain-specific promoters, regulatory sites likely to affect dynamic responses. The SNPs relevant for neurological disorders were highly enriched in constitutive coding regions and splice regulatory sites. We suggest that our results provide a bridge between genetics and the well-known effects of life history and recent stressful experiences on risk of psychiatric illness.

Human resilience depends on distinctively human brain circuitry and development

“…This fact was first noted in the landmark study of schizophrenia by the Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) and found repeatedly since. Recent work has shown that the genetics of behavioral and psychiatric traits are in this way clearly distinguishable from genetic liabilities for neurological disorders, for which more of the heritability lies in coding regions ( Reimers and Kendler, 2022 ).…”