QuestionÌý Are symptoms of premenstrual disorders associated with genetic liability for major psychiatric disorders?

FindingsÌý In this genetic association study of 56 725 women, premenstrual disorder symptoms were associated with polygenic liability for major psychiatric disorders but not for height.

MeaningÌý The results of this study suggest that symptoms of premenstrual disorders share genetic liability with major psychiatric disorders.

ImportanceÌý Premenstrual disorders are heritable, clinically heterogenous, with a range of affective spectrum comorbidities. It is unclear whether genetic predispositions to affective spectrum disorders or other major psychiatric disorders are associated with symptoms of premenstrual disorders.

ObjectiveÌý To assesss whether symptoms of premenstrual disorders are associated with the genetic liability for major psychiatric disorders, as indexed by polygenic risk scores (PRSs).

Design, Setting, and ParticipantsÌý Women from the Norwegian Mother, Father and Child Cohort Study were included in this genetic association study. PRSs were used to determine whether genetic liability for major depression, bipolar disorder, schizophrenia, attention-deficit/hyperactivity disorder, and autism spectrum disorder were associated with the symptoms of premenstrual disorders, using the PRS for height as a somatic comparator. The sample was recruited across Norway between June 1999 and December 2008, and analyses were performed from July 1 to October 14, 2022.

Main Outcomes and MeasuresÌý The symptoms of premenstrual disorders were assessed at recruitment at week 15 of pregnancy with self-reported severity of depression and irritability before menstruation. Logistic regression was applied to test for the association between the presence of premenstrual disorder symptoms and the PRSs for major psychiatric disorders.

ResultsÌý The mean (SD) age of 56 725 women included in the study was 29.0 (4.6) years. Premenstrual disorder symptoms were present in 12 316 of 56 725 participants (21.7%). The symptoms of premenstrual disorders were associated with the PRSs for major depression (β = 0.13; 95% CI, 0.11-0.15; P = 1.21 ×â¶Ä‰10^−36), bipolar disorder (β = 0.07; 95% CI, 0.05-0.09; P = 1.74 ×â¶Ä‰10^−11), attention deficit/hyperactivity disorder (β = 0.07; 95% CI, 0.04-0.09; P = 1.58 ×â¶Ä‰10^−9), schizophrenia (β = 0.11; 95% CI, 0.09-0.13; P = 7.61 ×â¶Ä‰10^−25), and autism spectrum disorder (β = 0.03; 95% CI, 0.01-0.05; P = .02) but not with the PRS for height. The findings were confirmed in a subsample of women without a history of psychiatric diagnosis.

ConclusionsÌý The results of this genetic association study show that genetic liability for both affective spectrum disorder and major psychiatric disorders was associated with symptoms of premenstrual disorders, indicating that premenstrual disorders have overlapping genetic foundations with major psychiatric disorders.