Institute of Genetics and Cancer

Uncovering the link between genes for intellectual ability and lifetime risk of schizophrenia

A significant breakthrough in the understanding of schizophrenia confirms a suspected link with genes that affect intellectual ability: June 2017

Silhouette of head made up of networks

Mutations within around a dozen genes have been linked to an increased risk of developing schizophrenia. In combination with environmental factors or stresses during pregnancy or childhood, these may trigger the onset of the condition. Most brain development disorders cause symptoms in early childhood but schizophrenia is unusual in that it doesn’t present until adolescence or even later (15-35 years of age).

New research has shown that DISC1, a gene that has been associated with cognitive disabilities that appear during early childhood, also acts as a master switch for multiple schizophrenia-associated genes.

The researchers aimed to study two sets of DISC1-related genes: those whose protein products directly interact with the DISC1 protein and those that show altered expression as a result of disruption of DISC1 or its interactors.

By sequencing over 200 genes, researchers have found that rare DNA mutations within DISC1 and its protein interactors alter childhood IQ, and mutations in the genes regulated by DISC1 and its interactors increase the risk of schizophrenia later in life.

Previously schizophrenia research focused on the effects of altering each gene directly associated with schizophrenia. This study reveals that even if there are no mutations in other schizophrenia-associated genes, mutations in DISC1 and its interactors can still cause these genes to malfunction and lead to schizophrenia.

The prevalence of schizophrenia is 1% in the global population, with one in 4,000 people being diagnosed every year. This research may reduce the incidence of full-blown schizophrenia by leading to earlier diagnosis and paving the way for therapeutic interventions that target a limited number of regulatory genes.

The researchers sequenced the genes of individuals with clinical diagnoses of depression, bipolar disorder or schizophrenia as well as healthy controls from the Lothian Birth Cohort. This cohort consists of healthy participants whose cognitive ability was measured at ages 11 and 70.

The research was undertaken by colleagues at the Centre for Genomic and Experimental Medicine (CGEM), within the Institute of Genetics and Molecular Medicine (IGMM), the Division of Psychiatry and the Centre from Cognitive Ageing and Cognitive Epidemiology (CCACE) at the University of Edinburgh and in collaboration with researchers at the Stanley Institute for Cognitive Genomics at Cold Spring Harbor Laboratories in New York.

Relevant Links

Paper: Rare disruptive variants in the DISC1 Interactome and Regulome: association with cognitive ability and schizophrenia

Pippa Thomson Research Group

Dr Pippa Thomson

This work was supported by a gift from Theodore and Vana Stanley and a grant from the National Institutes of Health (NIH).

The Stanley Medical Research Institue

National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the American medical research agency