Absolute and relative risks of mental disorders in families: a Danish register-based study.

Background: Relative risk estimates of familial aggregation of many types of mental disorders are available, but absolute risk estimates of familial aggregation of mental disorders remain sparse. The proportion of individuals who develop a mental disorder in the absence of the same disorder in a relative (non-familial cases) has not been examined. We aimed to create comprehensive risk estimates of the familial aggregation of mental disorders.

Methods: In this prospective cohort study, we followed people of Danish origin between Jan 1, 1970, and Dec 31, 2021. We used Danish population-based registers to link individuals and their mental health across extended family pedigrees. These registers include the Danish Civil Registration System, the Danish Multi Generation Register, the Danish Psychiatric Central Research Register, and the Danish National Patient Register. Mental disorders investigated were substance use disorder, cannabis use disorder, alcohol use disorder, schizophrenia and related disorders, schizophrenia, schizoaffective disorder, mood disorders, bipolar disorder, single and recurrent depressive disorders (depression), personality disorder, borderline personality disorder, and antisocial personality disorder. We estimated lifetime risk (risk up to age 60 years), age-specific absolute risk, and relative risk for each mental disorder and type of affected relative (eg first, second, or third-degree relatives). We calculated heritability estimates and the proportion of non-familial cases. We involved people with related lived experience in the study design and implementation.

Findings: A total of 3 048 583 individuals (1 486 132 [48·75%] females and 1 562 451 [51·25%] males) were followed up for 80 425 971 person-years. Individuals with a family member with a specific type of mental disorder had higher lifetime and relative risks of developing the same type of mental disorder. Both lifetime and relative risks were higher the closer the affected kinship. For example, the lifetime risk of depression was 15·48% (95% CI 15·31-15·65) in individuals with affected first-degree relatives, 13·50% (13·25-13·75) in individuals with affected second-degree relatives, 7·80% (7·76-7·84) in the general population, and 4·68% (4·65-4·71) in individuals without affected first-degree and second-degree relatives. The heritability for depression was 45·4% (95% CI 44·8-46·0) and the proportion of non-familial cases constituted 60·0% (95% CI 59·8-60·2).

Interpretation: Individuals with family members with a mental disorder face increased risks of the same disorder. From a population perspective, most mental disorders occur in individuals without affected close relatives, thus highlighting the need for prevention strategies which target the entire population.

Funding: Novo Nordisk Foundation.

Translation: For the Danish translation of the abstract see Supplementary Materials section.