Analysis of shared heritability in common disorders of the brain

Abstract

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

“…This finding is consistent with numerous studies using genetically informed methods that have suggested shared genetic influences on both ASD and ADHD traits and diagnoses, 5,6,9 and several that have highlighted shared copy number variants, 10,25 although other studies have not identified genetic overlap. 8,26 …”

“…3,4 Evidence of their shared heritability is mixed, with familial and twin studies suggesting an association, 5–7 but molecular studies calling this into question. 8 These disorders appear to share some genetic factors 9 and biological pathways, 10 although divergences in their neuro-biological, cognitive, and genetic profiles are apparent. 11–13 Although some findings may be accounted for by the co-occurrence of ADHD and ASD 13 and others by heterogeneity within the 2 conditions, 14 it remains unclear how related these disorders are etiologically.…”

Psychotic symptoms in 16p11.2 copy‐number variant carriers

“…Yet the communication impairment and repetitive speech or behavior associated with ASD can make assessment and differentiation of delusional beliefs and perceptual disturbances difficult. Furthermore, repetitive behaviors in ASD are sometimes difficult to distinguish from symptoms of obsessive compulsive disorder (OCD), which is itself a common co-occurring diagnosis that shares genetic liability with SCZ and, by extension, ASD [The Brainstorm Consortium et al, 2018]. Although OCD symptoms and characteristic repetitive behaviors in ASD are thought to be phenomenologically distinct [Guo et al, 2017;Jiujias, Kelley, & Hall, 2017], the boundary between them is not always clear.…”

Association of Rare Genetic Variants in Opioid Receptors with Tourette Syndrome

“…8–10 Main genes possibly involved in TS so far include NRXN1 , CNTN6 , CELSR3 , SLITRK1 , and HDC . 11–22 SLITRK1 encodes a transmembrane protein modulating neurite outgrowth belonging to a family comprising six paralogues ( SLITRK1 to SLITRK6 ) in mammals.…”