Assortative mating on educational attainment leads to genetic spousal resemblance for polygenic scores

We examined whether assortative mating for educational attainment (“like marries like”) can be detected in the genomes of ~ 1600 UK spouse pairs of European descent. Assortative mating on heritable traits like educational attainment increases the genetic variance and heritability of the trait in the population, which may increase social inequalities. We test for genetic assortative mating in the UK on educational attainment, a phenotype that is indicative of socio-economic status and has shown substantial levels of assortative mating. We use genome-wide allelic effect sizes from a large genome-wide association study on educational attainment (N ~ 300 k) to create polygenic scores that are predictive of educational attainment in our independent sample (r = 0.23, p < 2 × 10− 16). The polygenic scores significantly predict partners' educational outcome (r = 0.14, p = 4 × 10− 8 and r = 0.19, p = 2 × 10− 14, for prediction from males to females and vice versa, respectively), and are themselves significantly correlated between spouses (r = 0.11, p = 7 × 10− 6). Our findings provide molecular genetic evidence for genetic assortative mating on education in the UK

Comparing ecstasy users and non-users in a population-based and co-twin control design across multiple traits

Contains fulltext : 219151.pdf (Publisher’s version ) (Closed access)Objective: Ecstasy is one of the most commonly used illicit substances in Western countries. The aim of this study is to identify characteristics of ecstasy users in a large population-based sample of adults aged 18-45 years. Method: With generalized estimating equation models we explored the association between self-reported lifetime ecstasy use and urbanicity, educational attainment, health, wellbeing, stress, other substance use, personality traits and psychopathology in a Dutch twin sample (N=9,578, 66.8% female, 18-45 years). We also explored the nature of the association (underlying genetic factors, shared environmental factors or a causal relationship) with the co-twin control method. Results: Lifetime ecstasy users (N=945, 9.9%) were more often male, younger, living more often in urban areas, higher educated, less satisfied with life and more stressed than non-users. Ecstasy users scored differently on most personality and psychopathology scales compared to non-users and were more likely to have used every other substance we investigated. Whereas smoking tobacco and alcohol use often preceded first use of ecstasy, first ecstasy use often preceded first use of other illicit substances. A combination of scenarios (both causal and environmental/genetic) explained the strong associations between ecstasy and substance use. For the other variables no causal association was likely but genetic factors (i.e. psychopathology), shared environmental factors (i.e. demographics) or no clear pattern (i.e. personality) were likely scenarios. Conclusions: Ecstasy users differ on many characteristics from non-users, and especially on illicit substance use. In addition, our results indicate that causal effects may play a role in explaining the relationship between ecstasy use and other illicit substance use.8 p

The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

A genome-wide association study of self-rated health

Self-rated health questions have been proven to be a highly reliable and valid measure of overall health as measured by other indicators in many population groups. It also has been shown to be a very good predictor of mortality, chronic or severe diseases, and the need for services, and is positively correlated with clinical assessments. Genetic factors have been estimated to account for 25-64% of the variance in the liability of self-rated health. The aim of the present study was to identify Single Nucleotide Polymorphisms (SNPs) underlying the heritability of self-rated health by conducting a genome-wide association analysis in a large sample of 6,706 Australian individuals aged 18-92. No genome wide significant SNPs associated with self-rated health could be identified, indicating that self-rated health may be influenced by a large number of SNPs with very small effect size. A very large sample will be needed to identify these SNPs

Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I—clinical impact

Objective: To evaluate the clinical impact of nationwide implementation of genome-wide non-invasive prenatal testing (NIPT) in pregnancies at increased risk for fetal trisomies 21, 18 and 13 (TRIDENT study). Method: Women with elevated risk based on first trimester combined testing (FCT ≥ 1:200) or medical history, not advanced maternal age alone, were offered NIPT as contingent screening test, performed by Dutch University Medical laboratories. We analyzed uptake, test performance, redraw/failure rate, turn-around time and pregnancy outcome. Results: Between 1 April and 1 September 2014, 1413/23 232 (6%) women received a high-risk FCT result. Of these, 1211 (85.7%) chose NIPT. One hundred seventy-nine women had NIPT based on medical history. In total, 1386/1390 (99.7%) women received a result, 6 (0.4%) after redraw. Mean turn-around time was 14 days. Follow-up was available in 1376 (99.0%) pregnancies. NIPT correctly predicted 37/38 (97.4%) trisomies 21, 18 or 13 (29/30, 4/4 and 4/4 respectively); 5/1376 (0.4%) cases proved to be false positives: trisomies 21 (n = 2), 18 (n = 1) and 13 (n = 2). Estimated reduction in invasive testing was 62%. Conclusion: Introduction of NIPT in the Dutch National healthcare-funded Prenatal Screening Program resulted in high uptake and a vast reduction of invasive testing. Our study supports offering NIPT to pregnant women at increased risk for fetal trisomy. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd

Meta-analysis of genome-wide association studies for neuroticism, and the polygenic association with major depressive disorder

IMPORTANCE Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63 000 participants (including MDD cases)

Gene–environment correlations across geographic regions affect genome-wide association studies

Gene–environment correlations affect associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here we showed in up to 43,516 British siblings that educational attainment polygenic scores capture gene–environment correlations, and that migration extends these gene–environment correlations beyond the family to broader geographic regions. We then ran GWASs on 56 complex traits in up to 254,387 British individuals. Controlling for geographic regions significantly decreased the heritability for socioeconomic status (SES)-related traits, most strongly for educational attainment and income. For most traits, controlling for regions significantly reduced genetic correlations with educational attainment and income, most significantly for body mass index/body fat, sedentary behavior and substance use, consistent with gene–environment correlations related to regional socio-economic differences. The effects of controlling for birthplace and current address suggest both passive and active sources of gene–environment correlations. Our results show that the geographic clustering of DNA and SES introduces gene–environment correlations that affect GWAS results

Illicit drug use and the genetic overlap with Cannabis use

Contains fulltext : 219581.pdf (publisher's version ) (Open Access)Background: The use of illicit substances is correlated, meaning that individuals who use one illicit substance are more likely to also use another illicit substance. This association could (partly) be explained by overlapping genetic factors. Genetic overlap may indicate a common underlying genetic predisposition, or can be the result of a causal association. Methods: Polygenic scores for lifetime cannabis use were generated in a sample of Dutch participants (N = 8348). We tested the association of a PGS for cannabis use with ecstasy, stimulants and a broad category of illicit drug use. To explore the nature of the relationship: (1) these analyses were repeated separately in cannabis users and non-users and (2) monozogytic twin pairs discordant for cannabis use were compared on their drug use. Results: The lifetime prevalence was 24.8% for cannabis, 6.2% for ecstasy, 6.5% for stimulants and 7.1% for any illicit drug use. Significant, positive associations were found between PGS for cannabis use with ecstasy use, stimulants and any illicit drug use. These associations seemed to be stronger in cannabis users compared to non-users for both ecstasy and stimulant use, but only in people born after 1968 and not significant after correction for multiple testing. The discordant twin pair analyses suggested that cannabis use could play a causal role in drug use. Conclusions: The genetic liability underlying cannabis use significantly explained variability in ecstasy, stimulant and any illicit drug use. Further research should further explore the underlying mechanism to understand the nature of the association.6 p