Pleiotropy and Cross-Disorder Genetics Among Psychiatric Disorders

Genome-wide analyses of common and rare genetic variations have documented the heritability of major psychiatric disorders, established their highly polygenic genetic architecture, and identified hundreds of contributing variants. In recent years, these studies have illuminated another key feature o...

Full description

Saved in:
Bibliographic Details
Published in:Biological psychiatry (1969) 2021-01, Vol.89 (1), p.20-31
Main Authors: Lee, Phil H., Feng, Yen-Chen A., Smoller, Jordan W.
Format: Article
Language:English
Subjects:
Cross-disorder
Genetic correlation
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
GWAS
Humans
Mental Disorders - genetics
Multifactorial Inheritance
Nosology
Phenotype
Pleiotropy
Precision psychiatry
Psychiatric genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Genome-wide analyses of common and rare genetic variations have documented the heritability of major psychiatric disorders, established their highly polygenic genetic architecture, and identified hundreds of contributing variants. In recent years, these studies have illuminated another key feature of the genetic basis of psychiatric disorders: the important role and pervasive nature of pleiotropy. It is now clear that a substantial fraction of genetic influences on psychopathology transcend clinical diagnostic boundaries. In this review, we summarize evidence in psychiatry for pleiotropy at multiple levels of analysis: from overall genome-wide correlation to biological pathways and down to the level of individual loci. We examine underlying mechanisms of observed pleiotropy, including genetic effects on neurodevelopment, diverse actions of regulatory elements, mediated effects, and spurious associations of genomic variation with multiple phenotypes. We conclude with an exploration of the implications of pleiotropy for understanding the genetic basis of psychiatric disorders, informing nosology, and advancing the aims of precision psychiatry and genomic medicine.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2020.09.026