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The genetic relationship between female reproductive traits and six psychiatric disorders.

ABSTRACT: Female reproductive behaviours have important implications for evolutionary fitness and health of offspring. Here we used the second release of UK Biobank data (N?=?220,685) to evaluate the association between five female reproductive traits and polygenic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N?=?429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with age at first birth (AFB) (genetic correlation of -0.68?±?0.03), age at first sexual intercourse (AFS) (-0.56?±?0.03), number of live births (NLB) (0.36?±?0.04) and age at menopause (-0.27?±?0.04). There were also robustly significant associations between the PRS of eating disorder (ED) and AFB (0.35?±?0.06), ED and AFS (0.19?±?0.06), major depressive disorder (MDD) and AFB (-0.27?±?0.07), MDD and AFS (-0.27?±?0.03) and schizophrenia and AFS (-0.10?±?0.03). These associations were mostly explained by pleiotropic effects and there was little evidence of causal relationships. Our findings can potentially help improve reproductive health in women, hence better child outcomes. Our findings also lend partial support to the evolutionary hypothesis that causal mutations underlying psychiatric disorders have positive effects on reproductive success.

SUBMITTER: Ni G

PROVIDER: S-EPMC6700195 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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The genetic relationship between female reproductive traits and six psychiatric disorders.

Ni Guiyan G Amare Azmeraw T AT Zhou Xuan X Mills Natalie N Gratten Jacob J Lee S Hong SH

Scientific reports 20190819 1

Female reproductive behaviours have important implications for evolutionary fitness and health of offspring. Here we used the second release of UK Biobank data (N = 220,685) to evaluate the association between five female reproductive traits and polygenic risk scores (PRS) projected from genome-wide association study summary statistics of six psychiatric disorders (N = 429,178). We found that the PRS of attention-deficit/hyperactivity disorder (ADHD) were strongly associated with age at first bi ...[more]

PMID: 31427629

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Project description:BackgroundSleep is disrupted in depressed subjects, but it also deteriorates with age and possibly with the transition to menopause. The nature of interaction between mood, sleep, age and reproductive state is not well-defined. The aim of this study was to evaluate the relationship between mood and sleep among healthy women in different reproductive states.MethodsWe analyzed data from 11 younger (20-26 years), 21 perimenopausal (43-51 years) and 29 postmenopausal (58-71 years) healthy women who participated in a study on menopause, sleep and cognition. The 21-item Beck Depression Inventory (BDI) was administered to assess mood. Subjective sleep quality was assessed with the Basic Nordic Sleep Questionnaire (BNSQ). Objective sleep was measured with all-night polysomnography (PSG) recordings. Perimenopausal and younger women were examined during the first days of their menstrual cycle at the follicular phase.ResultsAmong younger women, less arousals associated with higher BDI total scores (p = 0.026), and higher SWS percentages with more dissatisfaction (p = 0.001) and depressive-somatic symptoms (p = 0.025), but with less depressive-emotional symptoms (p = 0.001). In specific, less awakenings either from REM sleep or SWS, respectively, associated with more punishment (p = 0.005; p = 0.036), more dissatisfaction (p < 0.001; p = 0.001) and more depressive-somatic symptoms (p = 0.001; p = 0.009), but with less depressive-emotional symptoms (p = 0.002; p = 0.003). In perimenopausal women, higher BNSQ insomnia scores (p = 0.005), lower sleep efficiencies (p = 0.022) and shorter total sleep times (p = 0.024) associated with higher BDI scores, longer sleep latencies with more depressive-somatic symptoms (p = 0.032) and longer REM latencies with more dissatisfaction (p = 0.017). In postmenopausal women, higher REM percentages associated with higher BDI total scores (p = 0.019) and more depressive-somatic symptoms (p = 0.005), and longer SWS latencies with more depressive-somatic symptoms (p = 0.030).ConclusionsDepressive symptoms measured with the total BDI scores associated with sleep impairment in both perimenopausal and postmenopausal women. In younger women, specific BDI factors revealed minor associations, suggesting that the type of sleep impairment can vary in relation to different depressive features. Our data indicate that associations between sleep and depressed mood may change in conjunction with hormonal milestones.

Project description:Importance:Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes. Objective:To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits. Design, Setting, and Participants:This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample. Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017. Main Outcomes and Measures:Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested. Results:Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32). Conclusions and Relevance:These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular.

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The genetic relationship between female reproductive traits and six psychiatric disorders.

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The genetic relationship between female reproductive traits and six psychiatric disorders.

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