Shared genetic basis between reproductive behaviors and anxiety-related disorders

Ohi, Kazutaka; Kuramitsu, Ayumi; Fujikane, Daisuke; Takai, Kentaro; Sugiyama, Shunsuke; Shioiri, Toshiki

doi:10.1038/s41380-022-01667-8

Cited by 5 publications

(4 citation statements)

References 58 publications

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“…For the causal relations between reproductive behaviors and psychiatric disorders, our study supports evidence for the earlier of age of reproductive behaviors in early life are causal factors in the rising risks of psychiatric disorders in previous studies [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. However, the none effects of age at menarche, AFB and ALB after accounting for AFS using multivariable MR suggest that the effect of age at menarche on depression is totally mediated by AFS and the effects of AFB and ALB on psychiatric disorders are confounded by AFS.…”

Section: Discussionsupporting

confidence: 89%

“…The GWAS summary data for psychiatric disorders were retrieved from the Psychiatric Genomes Consortium (PGC). We chose 12 related psychiatric disorders as the outcome, including anxiety disorders (33,640 cases/43,456 controls) [31], anorexia nervosa (14,477 samples) [32], attention deficit or hyperactivity disorder (4,945 cases/16,246 controls) [33], autism spectrum disorder (18,382 cases/27,969 controls) [34], bipolar disorder (41,917 cases/371,549 controls) and two BD subtypes: bipolar I disorder (25,060 cases/449,978 controls) and bipolar II disorder (6,781 cases/364,075 controls) [35], major depressive disorder (170,756 cases/329,443 controls) [36], obsessive compulsive disorder (2,688 cases/7,037 controls) [37], posttraumatic stress disorder (23,185 cases/151,309 controls) [38], schizophrenia (67,280 cases/86,912 controls) [39] and Tourette syndrome (55,386 cases/77,258 controls) [40]. Details for datasets are listed in Table 1.…”

Section: Psychiatric Disordersmentioning

confidence: 99%

“…Female reproductive behaviors, including age at menarche, age at first sexual intercourse, age at first birth, age at last birth and age at menopause, have important implications in reproductive health and evolutionary fitness. Some of these reproductive behaviors have been identified as risk factors for various psychiatric disorders [4][5][6], such as depression, schizophrenia [7] and bipolar disorders [8]. Taking depression as an example, multiple studies in the past decade have examined the association between age of menarche and risk of depression in adolescent girls and adulthood [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study

Hou

et al. 2023

Preprint

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Background: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. Methods: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. Results: Univariable MR analyses provide evidences that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on six psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder, Anxiety disorders and Anorexia Nervosa) when accounting for other reproductive behaviors with significant effects in univariable analyses. Conclusion: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders.

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Section: Discussionsupporting

confidence: 89%

Section: Psychiatric Disordersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study

Hou

et al. 2023

Preprint

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“…To estimate the genetic correlations of single-nucleotide polymorphisms (SNPs) (r g ) between two GWASs, LDSC analyses were performed. [32][33][34][35] For each GWAS, we ltered the imputed and directly genotyped SNPs in each GWAS to SNPs that overlapped with a HapMap3 SNP panel to restrict the analysis to wellimputed SNPs. Furthermore, insertion-deletion polymorphisms (indels), structural variants, strandambiguous SNPs and SNPs with extremely large effect sizes were removed.…”

Section: Linkage Disequilibrium Score Regression (Ldsc) Analysismentioning

confidence: 99%

Genetic correlations between suicide attempts and psychiatric and intermediate phenotypes adjusting for mental disorders

et al. 2023

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Background Suicide attempts are a moderately heritable trait, and genetic correlations with psychiatric and related intermediate phenotypes have been reported. However, as several mental disorders as well as major depressive disorder (MDD) are strongly associated with suicide attempts, these genetic correlations could be mediated by psychiatric disorders. Here, we investigated genetic correlations of suicide attempts with psychiatric and related intermediate phenotypes, with and without adjusting for mental disorders. Methods To investigate the genetic correlations, we utilized large-scale genome-wide association study summary statistics for suicide attempts (with and without adjusting for mental disorders), nine psychiatric disorders, and 15 intermediate phenotypes. Results Without adjusting for mental disorders, suicide attempts had significant positive genetic correlations with risks of attention-deficit/hyperactivity disorder, schizophrenia, bipolar disorder, MDD, anxiety disorders and posttraumatic stress disorder; higher risk tolerance; earlier age at first sexual intercourse, at first birth and at menopause; higher parity; lower childhood IQ, educational attainment and cognitive ability; and lower smoking cessation. After adjusting for mental disorders, suicide attempts had significant positive genetic correlations with the risk of MDD; earlier age at first sexual intercourse, at first birth and at menopause; and lower educational attainment. After adjusting for mental disorders, most of the genetic correlations with psychiatric disorders were decreased, while several genetic correlations with intermediate phenotypes were increased. Conclusions These findings highlight the importance of considering mental disorders in the analysis of genetic correlations related to suicide attempts and suggest that susceptibility to MDD, reproductive behaviors, and lower educational levels share a genetic basis with suicide attempts after adjusting for mental disorders.

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Is adjustment disorder genetically correlated with depression, anxiety, or risk-tolerant personality trait?

Ohi,

Fujikane,

Kuramitsu

et al. 2023

Journal of Affective Disorders

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Shared genetic basis between reproductive behaviors and anxiety-related disorders

Cited by 5 publications

References 58 publications

Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study

Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study

Genetic correlations between suicide attempts and psychiatric and intermediate phenotypes adjusting for mental disorders

Is adjustment disorder genetically correlated with depression, anxiety, or risk-tolerant personality trait?

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