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. 2024 Oct;39(10):1161-1170.
doi: 10.1007/s10654-024-01166-w. Epub 2024 Nov 4.

Familial coaggregation and shared genetic influence between major depressive disorder and gynecological diseases

Cheng-Yun Chen #  1 , Chi-Fung Cheng #  2 , Pei-Chun Chen  2 , Chi-Shin Wu  2   3 , Mei-Chen Lin  2 , Mei-Hsin Su  1   4 , Cherry Yin-Yi Chang  5 , Yi-Jiun Pan  6 , Yen-Tsung Huang  7 , Chun-Chieh Fan  8   9 , Shi-Heng Wang  10   11
Affiliations

Familial coaggregation and shared genetic influence between major depressive disorder and gynecological diseases

Cheng-Yun Chen et al. Eur J Epidemiol. 2024 Oct.

Abstract

The mechanism underlying the co-occurrence of major depressive disorder (MDD) and gynecological diseases remains unclear. This study aimed to investigate the familial co-aggregation and shared genetic loading between MDD and gynecological diseases, namely dysmenorrhea, endometriosis, uterine leiomyomas (UL), and polycystic ovary syndrome (PCOS). Overall, 2,121,632 females born 1970-1999 with parental information were enrolled from the Taiwan National Health Insurance Research Database (NHIRD); 25,142 same-sex twins and 951,779 persons with full-sibling(s) were selected. Genome-wide genotyping data were available for 67,882 unrelated female participants from the Taiwan Biobank linked to the NHIRD. A generalized linear model with a logistic link function was used to examine the associations of individual history, family history in parents/full-siblings/same-sex twins, and polygenic risk scores (PRS) for MDD with the risk of gynecological diseases; generalized estimating equations were used to consider the non-independence of data. Both parents affected with MDD was associated with four gynecological diseases, and its magnitude of association was higher than either affected parent; maternal MDD showed a higher magnitude of association than paternal MDD. Full-siblings of patients with MDD had a higher risk of four gynecological diseases; same-sex twins of patients with MDD had a greater association with dysmenorrhea and PCOS. PRS for MDD was associated with dysmenorrhea and endometriosis. Familial co-aggregation was observed in the co-occurrence of MDD and four gynecological diseases. There exists a shared polygenic liability between MDD and dysmenorrhea and endometriosis. Individuals with MDD-affected relatives or a higher PRS for MDD should be monitored for gynecological diseases.

Keywords: Familial coaggregation; GWAS; Gynecological diseases; Major depressive disorder; Polygenic risk score; Shared genetic influence.

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Conflict of interest statement

Declarations. Competing interests: The authors have no relevant financial or nonfinancial interests to disclose.

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