Investigating the molecular mechanisms and consequences of assortative mating in major psychiatric disorders: completing a missing piece of the psychiatric genetics puzzle

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PROJECT SUMMARY Recent research has indicated that individuals diagnosed with a major psychiatric disorder are more likely than healthy individuals to select a mate with their own or an alternative psychiatric condition. What role this nonrandom mating may play in the transmission of psychiatric illness, however, remains unclear. Where parents are homotypic for a disorder (e.g., both parents have a diagnosis of schizophrenia), offspring will receive genetic variants from each parent that are related to that disorder – placing them at particularly high genetic risk for that condition's development. However, this type of compounded genetic risk may also occur in heterotypic pairings (e.g., one parent having schizophrenia, the other bipolar disorder), as many psychiatric conditions share genetic risks. With prior research suggesting that such heterotypic pairings are pervasive in psychiatric populations, understanding the degree to which risks are sustained in these offspring is an important question. The primary goal of this proposal is, therefore, to leverage the unique scale of data available in the Swedish Medical Registers to determine the change in risk for major psychiatric diagnoses, among the offspring of parents who are homotypic or heterotypic for major psychiatric diagnoses, relative to the risk in offspring of single affected or healthy parents. Parents with any of eight major psychiatric diagnoses - attention deficit hyperactivity disorder, bipolar disorder, generalized anxiety disorder, major depressive disorder, obsessive- compulsive disorder, schizophrenia, social phobia, and substance abuse – will be considered in this work, with the incidence of these conditions in their offspring compared to the incidence in matched population controls. In addition to describing these risks, this project also proposes to examine the degree of overlap in risk variants for a particular condition – schizophrenia – among the parents of offspring diagnosed with this condition. If found, this type of molecular correlation would signal a clear mechanism by which a disorder may arise in offspring of homo- or heterotypic pairs, while its absence could suggest a stronger role for environment in shaping these added risks.