The genetic epidemiology of obsessive-compulsive disorder: a systematic review and meta-analysis

Abstract

The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the relevance of all the studies published since 2001, the current study aimed to update the state-of-art knowledge on the field. All published data concerning the genetic epidemiology of OCD from the CENTRAL, MEDLINE, EMBASE, BVS, and OpenGrey databases were searched by two independent researchers until September 30, 2021. To be included, the articles had to fulfill the following criteria: OCD diagnosis provided by standardized and validated instruments; or medical records; inclusion of a control group for comparison and case-control, cohort or twin study designs. The analysis units were the first-degree relatives (FDRs) of OCD or control probands and the co-twins in twin pairs. The outcomes of interest were the familial recurrence rates of OCD and the correlations of OCS in monozygotic compared with dizygotic twins. Nineteen family, twenty-nine twin, and six population-based studies were included. The main findings were that OCD is a prevalent and highly familial disorder, especially among the relatives of children and adolescent probands, that OCD has a phenotypic heritability of around 50%; and that the higher OCS correlations between MZ twins were mainly due to additive genetic or to non-shared environmental components.

Heritability of Clinically Diagnosed Obsessive-Compulsive Disorder Among Twins

“…The heritability of clinically diagnosed OCD in this study was similar to that reported in previous nonclinical twin studies of individuals self-reporting symptoms despite only partially overlapping constructs being measured. Environmental factors shared by twins growing up in the same family did not contribute to OCD liability, whereas nonshared environmental factors explained the remaining variance.…”

“…Evidence comes from extended family pedigrees of individuals with clinically diagnosed OCD and, indirectly, from nonclinical twin studies of research volunteers self-reporting current obsessive-compulsive symptoms. These phenotypes overlap, but are not equivalent; it is possible that heritability estimates based on self-report data differ from estimates derived from clinician diagnoses. This is the first study, to our knowledge, to estimate the heritability of clinically diagnosed OCD from a sample of twins.…”

“…Obsessive-compulsive disorder (OCD) is thought to be moderately heritable (around 40%-50%). Evidence comes from extended family pedigrees of individuals with clinically diagnosed OCD and, indirectly, from nonclinical twin studies of research volunteers self-reporting current obsessive-compulsive symptoms . These phenotypes overlap, but are not equivalent; it is possible that heritability estimates based on self-report data differ from estimates derived from clinician diagnoses.…”

Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci

“…OCD is responsible for profound personal and societal costs (World Health Organization, 2008), including a substantial risk of suicide (~10 times higher than the population prevalence; Fernandez de la Cruz, 2017) as well as an increase in general mortality (Meier, 2016). OCD is highly heritable, with twinbased heritability estimates ranging between 27-47% in adults and 45-65% in children (Blanco-Vieira et al, 2023;Burton et al, 2018;Pauls, 2008;van Grootheest et al, 2005). The SNPbased heritability of OCD has been reported to be between 28% and 37% (SEs between 4-11%; Mahjani, 2022a;IOCDF & OCGAS et al, 2018;Davis et al, 2013), with heritability estimates for childhood-onset OCD at the higher end of the range, in line with findings from twin studies.…”

A Burden of Rare Copy Number Variants in Obsessive-Compulsive Disorder

“…Current scientific literature supports a genetic contribution to OCD risk. Population-scale epidemiological studies indicate substantial familial clustering of the condition [ 1 – 3 ]. Based on twin study estimates, additive genetic factors account for 47% of variance in obsessive-compulsive symptoms [ 1 ].…”