Shared Genetic Risk Across Psychiatric Disorders

Background:  Population based epidemiological studies have shown an association between autism spectrum disorder (ASD) and several other disorders including schizophrenia, psychosis and intellectual disability. Likewise, a variety of genetic studies in children with autism have genetic risk genes and loci shared with other, frequently co-morbid, psychiatric disorders. Genetic and family based studies have extended this also to other family members.

Where previous family-based studies focused either on one disorder as a risk factor for several other disorders or several other disorders as risks for one disorlder, the aim of this study was to assess in one large population a variety of psychiatric disorders both as risk factors and as outcomes. This was examined by the risk for psychiatric disorders in full siblings of probands diagnosed with a range of psychiatric disorders. To verify if the risk is specific to psychiatric disorders, we also assessed the ASD risk and the risk of other psychiatric disorders in siblings of probands with type-1 diabetes and siblings of probands with hernia, two heritable conditions. Not all countries and health systems can provide data to answer these questions. In our study we could use unique data from Israel, including information on family relations as well as clinically ascertained diagnoses of psychiatric disorders and potentially important confounding covariates.

Objectives:  To utilize diagnostic data from screening of an entire population to further understand autism risk in relation to risk shared across other psychiatric diagnostic groups

Methods:  The study population was recruited from all Israeli adolescents, ages 16-17, with at least one sibling and undergoing mandatory screening for eligibility to serve in the Israeli military, between the years 1998-2014. If the recruit is suspected of any relevant problems a comprehensive psychosocial examination is performed by a clinical social worker or psychologist and board-certified psychiatrist. Among individuals with an ASD diagnosis we calculated the risk of a selected psychiatric disorder in his/her sibling. Next, we repeated these calculations for all selected psychiatric disorders pairwise. We included the disorders: ASD (n=3400), psychotic disorder (n=9028), personality disorders (n=25,211), anxiety disorders (n=16,394), mood disorders (n=12,639), intellectual disability (n=13,667), low cognitive ability (n=23,226), type-1 diabetes (n=3638), and hernia (n=36,806). For each case we included 10 matched controls. We estimated relative risks of each disorder by the odds ratios from logistic regression. The odds ratios were calculated adjusted for sex, socio-economic status and year of birth.

Results:  Siblings of probands with any of the psychiatric disorders were at increased risk for all psychiatric disorders examined and for low cognitive ability (most RRs ranging 2-3). For individuals with ASD the sibling RRs (95% confidence intervals) were estimated to be: for psychotic disorder, 3.4 (2.8-4.0); mood disorder, 2.4 (1.9-3.0); anxiety disorder, 2.9 (2.4-3.6); intellectual disability, 6.9 (6.0-7.9); ASD, 11.5 (9.2-14.4); hernia, 0.8 (0.6-0.9); and, diabetes, 1.0 (0.5-2.1).

Conclusions:  There appears to be a large cross-sibling risk among individuals with different psychiatric diagnoses. Highest cross-sibling recurrence risk was observed for individuals with ASD, intellectual disability and psychotic disorder.