Shared genetic basis between reproductive behaviors and anxiety-related disorders. 2022

Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
Department of Psychiatry, Gifu University Graduate School of Medicine, Gifu, Japan. k_ohi@gifu-u.ac.jp.

Reproductive behaviors are associated with risks for psychiatric disorders. Reproductive phenotypes are moderately heritable and have genetic overlaps with risks for psychiatric disorders. However, the genetic and causal relationships between anxiety-related disorders or specific anxiety disorders and reproductive phenotypes remain unknown. We utilized large-scale genome-wide association study (GWAS) results (n = 9537-542,901) for five reproductive phenotypes [age at menarche, age at first sexual intercourse (AFS), age at first birth (AFB), number of children ever born (NEB), and age at menopause] and five anxiety-related disorders [panic disorder, anxiety disorders from the ANGST and the UK biobank (UKBB), posttraumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD)]. To assess genetic correlations and causal associations, linkage disequilibrium score regression and Mendelian randomization analyses, respectively, were performed. We found that AFS and AFB were negatively correlated with anxiety disorders ANGST (AFS: rg ± SE = -0.28 ± 0.08, p = 6.00 × 10-4; AFB: -0.45 ± 0.11, p = 3.26 × 10-5), anxiety disorders UKBB (AFS: -0.18 ± 0.03, p = 9.64 × 10-9; AFB; -0.25 ± 0.03, p = 2.90 × 10-13) and PTSD (AFS: -0.42 ± 0.12, p = 4.00 × 10-4; AFB: -0.44 ± 0.12, p = 2.00 × 10-4) and positively correlated with OCD (AFS: 0.25 ± 0.05, p = 2.46 × 10-6; AFB: 0.25 ± 0.05, p = 3.92 × 10-7). Conversely, NEB was negatively correlated with OCD (-0.28 ± 0.08, p = 6.00 × 10-4). We revealed bidirectional effects between earlier AFS and AFB and anxiety disorders (odds ratios: ORearlier AFS→Anxiety = 1.64, p = 2.27 × 10-8; ORearlier AFB→Anxiety = 1.15, p = 2.28 × 10-3; ORAnxiety→earlier AFS = 1.02, p = 6.62 × 10-8; ORAnxiety→earlier AFB = 1.08, p = 1.60 × 10-4). In contrast, we observed unidirectional effects of later AFS and AFB on OCD (ORlater AFS→OCD = 2.18, p = 2.16 × 10-6; ORlater AFB→OCD = 1.22, p = 0.016). We suggest that those who have earlier sexual debut and childbirth are prone to risk for anxiety disorders and vice versa, while those who have later sexual debut and childbirth are genetically prone to risk for OCD. Our findings further support revising the diagnostic criteria (DSM-5) such that OCD is independent from anxiety disorders.

UI MeSH Term Description Entries

Related Publications

Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
March 2020, Psychological medicine,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
October 2015, European journal of human genetics : EJHG,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
June 2021, Psychiatry and clinical neurosciences,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
December 2017, Genome medicine,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
April 1995, Human reproduction (Oxford, England),
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
March 2009, Behavioural pharmacology,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
July 2021, Epilepsia,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
October 2017, Best practice & research. Clinical obstetrics & gynaecology,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
August 2025, Scientific reports,
Kazutaka Ohi, and Ayumi Kuramitsu, and Daisuke Fujikane, and Kentaro Takai, and Shunsuke Sugiyama, and Toshiki Shioiri
May 2008, American journal of medical genetics. Part C, Seminars in medical genetics,
Copied contents to your clipboard!