Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study.

BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]). CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

Evidence for genetic variation in human mate preferences for sexually dimorphic physical traits.

Intersexual selection has been proposed as an important force in shaping a number of morphological traits that differ between human populations and/or between the sexes. Important to these accounts is the source of mate preferences for such traits, but this has not been investigated. In a large sample of twins, we assess forced-choice, dichotomous mate preferences for height, skin colour, hair colour and length, chest hair, facial hair, and breast size. Across the traits, identical twins reported more similar preferences than nonidentical twins, suggesting genetic effects. However, the relative magnitude of estimated genetic and environmental effects differed greatly and significantly between different trait preferences, with heritability estimates ranging from zero to 57%.

Heritability of preferences for multiple cues of mate quality in humans.

Human mate preferences have received a great deal of attention in recent decades because of their centrality to sexual selection, which is thought to play a substantial role in human evolution. Most of this attention has been on universal aspects of mate preferences, but variation between individuals is less understood. In particular, the relative contribution of genetic and environmental influences to variation in mate preferences is key to sexual selection models but has barely been investigated in humans, and results have been mixed in other species. Here, we used data from over 4000 mostly female twins who ranked the importance of 13 key traits in a potential partner. We used the classical twin design to partition variation in these preferences into that due to genes, family environment, and residual factors. In women, there was significant variability in the broad-sense heritability of individual trait preferences, with physical attractiveness the most heritable (29%) and housekeeping ability the least (5%). Over all the trait preferences combined, broad-sense heritabilities were highly significant in women and marginally significant in men, accounting for 20% and 19% of the variation, respectively; family environmental influences were much smaller. Heritability was a little higher in reproductive aged than in nonreproductive aged women, but the difference was not significant.

An epidemiological survey of post-coital psychological symptoms in a UK population sample of female twins.

Postcoital psychological symptoms (PPS) is a virtually unexplored phenomenon in the female population even though women frequently complain about irritability and motiveless crying after intercourse and/or orgasm. The aim of this study was to explore the epidemiology and genetic influences of PPS in a UK population sample of women. 1,489 unselected female twins aged 18-85 completed questions on recent and persistent PPS and potential risk factors. Standard methods of quantitative genetic analysis were used to model latent genetic and environmental factors influencing variation in PPS. For identification of potential risk factors, regression analyses were conducted. Phenotypic variation in PPS was explored using a genetic variance component analysis (VCA) approach. We found 3.7% of women reported suffering from recent PPS and 7.7% from persistent PPS. Relationship satisfaction and experience of abuse were found to be independently associated with recent (OR 4.5, 95% CI 4.13-4.87 and OR 1.3, 95% CI 1.02-1.34, respectively) and persistent PPS (OR 2.53, 95% CI 2.17-2.81 and OR 1.16, 95% CI 1.09-1.26, respectively). VCA revealed that phenotypic variance was best explained by an additive genetic (AE) model, ascribing 28% (for recent PPS) and 26% (for persistent PPS) of phenotypic variance to additive genetic effects, with the rest being a result of individual experiences and random measurement error. To our knowledge, this is the first and largest study investigating the epidemiology of PPS. It seems that the most important targets for intervention and prevention occur outside of the family, such as relationship quality and satisfaction, and history of abuse.

Exploring genetic and environmental influences on miscarriage rates: a twin study.

Abstract Miscarriage is the most common type of pregnancy loss, occurring in up to 15% of clinically recognized pregnancies. Our understanding of the etiology is still limited but is believed to be multifactorial, including endocrine and anatomical abnormalities, immunologic, genetic and lifestyle factors. The aim of this study was to explore whether genetic variability in miscarriage is under any genetic influence. 3234 MZ and DZ female twins completed postal self-completion questionnaires on pregnancies. Rates were adjusted for total number of pregnancies. The relative contribution of genetic and environmental factors to variation in miscarriage was assessed using twin intra-pair correlations and quantified using a variance components model fitting approach. We found 22.7% of our twins reporting having suffered at least one miscarriage. Current age, age at first pregnancy and higher number of pregnancies all had a significant influence on reported miscarriage. The concordance of miscarriage was similar in identical and non-identical twins, 26% and 27%, respectively. Shared environment and predominantly random error and unique environment rather than genetic factors best explained the total variation of miscarriage. To our knowledge, this is the first large twin study exploring heritability of miscarriage which unlike the vast majority of common variable traits, shows no significant genetic influence. In the absence of clear environmental factors, these results suggest the influence of random factors.

Emotional intelligence and its association with orgasmic frequency in women.

INTRODUCTION: Up to 30% of women suffer from female orgasmic disorder (FOD)-the second most common type of female sexual dysfunction. FOD has been acknowledged to be multifactorial and recent research has implicated the importance of psychosocial risk factors. AIM: The aim of this study is to investigate whether normal variations in emotional intelligence--the ability to identify and manage emotions of one's self and others--are associated with orgasmic frequency during intercourse and masturbation. To our knowledge, this is the first such study in a large unselected population. METHODS: A total of 2035 women from the TwinsUK registry completed questionnaires relating to emotional intelligence and sexual behavior. Global emotional intelligence was measured using the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF). Orgasmic frequency was assessed using two self-constructed questions. MAIN OUTCOME MEASURES: Using Spearman's rank correlation and quartile logistic regression, we investigated whether variations in emotional intelligence are associated with female orgasmic frequency during intercourse and masturbation. RESULTS: Emotional intelligence was not associated with the potential confounders of age and years of education, nor did we find a significant association between emotional intelligence and potential risk factors for FOD such as age, body mass index, physical or sexual abuse, or menopause. We found emotional intelligence to be positively correlated with both frequency of orgasm during intercourse (r = 0.13, P < 0.001) and masturbation (r = 0.23, P < 0.001). Women in the lowest quartile of emotional intelligence had an approximate twofold increased risk of infrequent orgasm (Intercourse = odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4-3.9; Masturbation = [OR] 1.8, [CI] 1.3-2.5). CONCLUSION: Low emotional intelligence seems to be a significant risk factor for low orgasmic frequency. Consideration of this behavioral risk factor may need to be incorporated into research into FOD and possible treatment approaches.

The genetics and epidemiology of female sexual dysfunction: a review.

INTRODUCTION: Female sexual dysfunction (FSD) is an often underestimated and common problem with serious effects on women's quality of life. Despite a high overall prevalence in the female population--exceeding that of male sexual dysfunction--until recently, little research has focused on this area. In contrast to the successful advances of genetic research in a wide variety of human diseases, genetic exploration in FSD lags far behind. AIM: The aim of this review is to acquaint the reader with the current behavioral and molecular genetic research in the field of FSD. Methods. Because of the heterogeneity of the included studies, we are providing a nonsystematic review. RESULTS: Recent epidemiological and candidate gene studies have suggested a strong genetic influence on female sexual functioning. While these findings provide a clear rationale for more genetic research in the field, they need to be replicated on a much larger scale to be definitive. CONCLUSIONS: Successful identification of biomarkers and novel genes underlying FSD should improve the diagnosis, identification, and treatment of different subgroups. Future pharmacotherapeutic approaches to FSD will benefit from novel targets and the concept that individual variations have a genetic component may help destigmatize our views of sexual problems. Burri AV, Cherkas LM, and Spector TD.