The effects of age at menarche and first sexual intercourse on reproductive and behavioural outcomes:A Mendelian randomization study

There is substantial variation in the timing of significant reproductive life events such as menarche and first sexual intercourse. Life history theory explains this variation as an adaptive response to an individual's environment and it is important to examine how traits within life history strategies affect each other. Here we applied Mendelian randomization (MR) methods to investigate whether there is a causal effect of variation in age at menarche and age at first sexual intercourse (markers or results of exposure to early life adversity) on outcomes related to reproduction, education and risky behaviour in UK Biobank (N = 114 883-181 255). Our results suggest that earlier age at menarche affects some traits that characterize life history strategies including earlier age at first and last birth, decreased educational attainment, and decreased age at leaving education (for example, we found evidence for a 0.26 year decrease in age at first birth per year decrease in age at menarche, 95% confidence interval: -0.34 to -0.17; p < 0.001). We find no clear evidence of effects of age at menarche on other outcomes, such as risk taking behaviour. Age at first sexual intercourse was also related to many life history outcomes, although there was evidence of horizontal pleiotropy which violates an assumption of MR and we therefore cannot infer causality from this analysis. Taken together, these results highlight how MR can be applied to test predictions of life history theory and to better understand determinants of health and social behaviour

Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success

Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used genomic structural equation modeling and prior genome-wide association studies (GWASs) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability. We identified 157 genome-wide-significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Noncognitive genetics were enriched in the same brain tissues and cell types as cognitive performance, but showed different associations with gray-matter brain volumes. Noncognitive genetics were further distinguished by associations with personality traits, less risky behavior and increased risk for certain psychiatric disorders. For socioeconomic success and longevity, noncognitive and cognitive-performance genetics demonstrated associations of similar magnitude. By conducting a GWAS of a phenotype that was not directly measured, we offer a view of genetic architecture of noncognitive skills influencing educational success

Genetic associations between non-cognitive skills and educational outcomes: The role of parental environment

This is the OSF project for the paper "Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores" (https://www.biorxiv.org/content/10.1101/2020.09.15.296236v3). You can find below our pre-registration as well as slides from different talks about the project. Recorded talks are available at https://www.youtube.com/channel/UCoqmCjVOrsgpE2ksFynqGvg/playlists or on the BGA website (ask us for access). You can find all analyses and simulations code on https://github.com/PerlineDemange/GeneticNurtureNonCog

Estimating a plausible causal effect of a longer education on well-being, depression and physical health

Pre-Registratio

Distinguishing Well-being and Resilience: a GWAS-by-subtraction study in UK Biobank

Mental health is defined by the World Health Organization as “a state of well-being in which the individual realizes his or her own abilities, can cope with the normal stresses of life, can work productively and fruitfully, and is able to make a contribution to his or her community” (World Health Organization, 2005). Therefore, mental health is more than the absence of psychopathology and includes the concept of well-being. Often used definitions of well-being are a high level of positive affect and happiness, a positive evaluation of life satisfaction (Diener et al., 2018) or feelings of thriving, positive functioning, and positive judgments about the meaning and purpose of an individual’s life (Ryff, 1989). Feelings of well-being and happiness have been consistently associated with less mental illness and longer and healthier lives (Diener et al., 2017; Greenspoon &amp; Saklofske, 2001; Steptoe, 2019; Zaninotto &amp; Steptoe, 2019), although the direction of causation is not clear yet (Rohrer &amp; Lucas, 2020). Furthermore, well-being is strongly related to the mental health outcome after the experience of stress, i.e. resilience (Bajaj &amp; Pande, 2016; Fredrickson et al., 2003; Hu et al., 2015; Satici, 2016). Resilience is often conceptualized as the absence of psychopathological symptoms after the experience of stressful life events (e.g. Amstadter et al., 2014; Van der Werff et al., 2013; van Harmelen et al., 2020). In life, everyone is exposed to stressful life events, either personal or worldwide. Resilience is the constructive and most common response to these life events (Galatzer-Levy et al., 2018). Resilient people adapt relatively quickly and are quickly back to their baseline levels of mental health, whereas less resilient people do not cope well and are at risk for developing chronic or long-term adverse effects, such as low well-being, depressive symptoms, or other psychopathologies. In a previous study, we replicated the strong relation (r=0.50) and reported a large overlap between resilience and well-being (de Vries et al., 2021). In a bivariate twin model, the genetic correlation between resilience and well-being was 0.71 (95% CI: 0.70-0.71), and the environmental correlation was close to unity, 0.93 (95% CI: 0.86-0.98), indicating a large overlap in the genetic and environmental factors underlying resilience and well-being. The strong phenotypic, genetic, and environmental correlations between well-being and resilience suggests a partly overlapping etiology, which sometimes leads to the claim that wellbeing is resilience and that the same trait is assessed but with a different name. To further investigate the relation, (genetic) overlap and differences between resilience and well-being, we will perform molecular genetic analyses in the current study. First, we will perform a GWAS on UK Biobank data to investigate the genetic variants related to resilience and compare those to the genetic variants related to happiness based on the UKB GWAS of Baselmans and Bartels (2018). Next, we will apply the GWAS-by-subtraction method (Demange et al., 2021) using the UKB happiness GWAS and our UKB resilience GWAS to directly investigate the overlap between happiness and resilience. Subtracting the resilience GWAS from the happiness will lead to a GWAS of “pure happiness”, by removing genetic variants associated with resilience. In follow-up analyses, we will investigate and compare the genetic variants associated with resilience, happiness, and “pure happiness” using functional annotation, gene-mapping, and gene-based tests and we will compute genetic correlations with a range of phenotypes (see Analyses below for more details). These results will lead to more knowledge on the overlap and distinction between well-being and resilience. References: Amstadter, A. B., Myers, J. M., &amp; Kendler, K. S. (2014). Psychiatric resilience: Longitudinal twin study. British Journal of Psychiatry, 205(4), 275–280. https://doi.org/10.1192/bjp.bp.113.130906 Bajaj, B., &amp; Pande, N. (2016). Mediating role of resilience in the impact of mindfulness on life satisfaction and affect as indices of subjective well-being. Personality and Individual Differences, 93, 63–67. https://doi.org/10.1016/j.paid.2015.09.005 Baselmans, B. M. L., &amp; Bartels, M. (2018). A genetic perspective on the relationship between eudaimonic –and hedonic well-being. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-32638-1 de Vries, L. P., Baselmans, B. M. L., Luykx, J. J., de Zeeuw, E. L., Minică, C., de Geus, E. J. C., Vinkers, C. H., &amp; Bartels, M. (2021). Genetic evidence for a large overlap and potential bidirectional causal effects between resilience and well-being. Neurobiology of Stress, 14, 100315. https://doi.org/10.1016/j.ynstr.2021.100315 Demange, P. A., Malanchini, M., Mallard, T. T., Biroli, P., Cox, S. R., Grotzinger, A. D., Tucker-Drob, E. M., Abdellaoui, A., Arseneault, L., van Bergen, E., Boomsma, D. I., Caspi, A., Corcoran, D. L., Domingue, B. W., Harris, K. M., Ip, H. F., Mitchell, C., Moffitt, T. E., Poulton, R., … Nivard, M. G. (2021). Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction. Nature Genetics. https://doi.org/10.1038/s41588-020-00754-2 Diener, E., Lucas, R. E., &amp; Oishi, S. (2018). Advances and Open Questions in the Science of Subjective Well-Being. Collabra: Psychology, 4(1). https://doi.org/10.1525/collabra.115 Diener, E., Pressman, S. D., Hunter, J., &amp; Delgadillo-Chase, D. (2017). If, Why, and When Subjective Well-Being Influences Health, and Future Needed Research. Applied Psychology: Health and Well-Being, 9(2), 133–167. https://doi.org/10.1111/aphw.12090 Fredrickson, B. L., Tugade, M. M., Waugh, C. E., &amp; Larkin, G. R. (2003). What Good Are Positive Emotions in Crises? A Prospective Study of Resilience and Emotions Following the Terrorist attacks on the United States on September 11th, 2001. Journal of Personality and Social Psychology, 84(2), 365. https://doi.org/10.1037/0022-3514.84.2.365 Galatzer-Levy, I. R., Huang, S. H., &amp; Bonanno, G. A. (2018). Trajectories of resilience and dysfunction following potential trauma: A review and statistical evaluation. Clinical Psychology Review, 63, 41–55. https://doi.org/10.1016/j.cpr.2018.05.008 Greenspoon, P. J., &amp; Saklofske, D. H. (2001). Toward an integration of subjective well-being and psychopathology. Social Indicators Research, 54(1), 81–108. https://doi.org/10.1023/A:1007219227883 Hu, T., Zhang, D., &amp; Wang, J. (2015). A meta-analysis of the trait resilience and mental health. Personality and Individual Differences, 76, 18–27. https://doi.org/10.1016/j.paid.2014.11.039 Rohrer, J. M., &amp; Lucas, R. E. (2020). Causal Effects of Well-Being on Health : It ’ s Complicated. https://doi.org/https://doi.org/10.31234/osf.io/wgbe4 Ryff, C. D. (1989). Happiness is everything, or is it? Explorations on the meaning of psychological well-being. Journal of Personality and Social Psychology, 57(6), 1069–1081. https://doi.org/10.1037/0022-3514.57.6.1069 Satici, S. A. (2016). Psychological vulnerability, resilience, and subjective well-being: The mediating role of hope. PERSONALITY AND INDIVIDUAL DIFFERENCES, 102, 68–73. https://doi.org/10.1016/j.paid.2016.06.057 Steptoe, A. (2019). Happiness and Health. Annual Review of Public Health, 40, 339–359. https://doi.org/10.1146/annurev-publhealth-040218-044150 Van der Werff, S. J. A., Pannekoek, J. N., Veer, I. M., van Tol, M. J., Aleman, A., Veltman, D. J., Zitman, F. G., Rombouts, S. A. R. B., Elzinga, B. M., &amp; van der Wee, N. J. A. (2013). Resilience to childhood maltreatment is associated with increased resting-state functional connectivity of the salience network with the lingual gyrus. Child Abuse and Neglect. https://doi.org/10.1016/j.chiabu.2013.07.008 van Harmelen, A.-L., Blakemore, S. J., Goodyer, I. M., &amp; Kievit, R. A. (2020). The Interplay Between Adolescent Friendship Quality and Resilient Functioning Following Childhood and Adolescent Adversity. Adversity and Resilience Science. https://doi.org/10.1007/s42844-020-00027-1 World Health Organization. (2005). Promoting Mental Health: Concepts, Emerging Evidence, Practice. Zaninotto, P., &amp; Steptoe, A. (2019). English Longitudinal Study of Ageing. Encyclopedia of Gerontology and Population Aging. Cham: Springer International Publishing, 1–7. https://doi.org/10.1007/978-3-319-69892-2_335-1 Amstadter, A. B., Myers, J. M., &amp; Kendler, K. S. (2014). Psychiatric resilience: Longitudinal twin study. British Journal of Psychiatry, 205(4), 275–280. https://doi.org/10.1192/bjp.bp.113.130906 Bajaj, B., &amp; Pande, N. (2016). Mediating role of resilience in the impact of mindfulness on life satisfaction and affect as indices of subjective well-being. Personality and Individual Differences, 93, 63–67. https://doi.org/10.1016/j.paid.2015.09.005 Baselmans, B. M. L., &amp; Bartels, M. (2018). A genetic perspective on the relationship between eudaimonic –and hedonic well-being. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-32638-1 de Vries, L. P., Baselmans, B. M. L., Luykx, J. J., de Zeeuw, E. L., Minică, C., de Geus, E. J. C., Vinkers, C. H., &amp; Bartels, M. (2021). Genetic evidence for a large overlap and potential bidirectional causal effects between resilience and well-being. Neurobiology of Stress, 14, 100315. https://doi.org/10.1016/j.ynstr.2021.100315 Demange, P. A., Malanchini, M., Mallard, T. T., Biroli, P., Cox, S. R., Grotzinger, A. D., Tucker-Drob, E. M., Abdellaoui, A., Arseneault, L., van Bergen, E., Boomsma, D. I., Caspi, A., Corcoran, D. L., Domingue, B. W., Harris, K. M., Ip, H. F., Mitchell, C., Moffitt, T. E., Poulton, R., … Nivard, M. G. (2021). Investigating the genetic architecture of noncognitive skills using GWAS-by-subtraction. Nature Genetics. https://doi.org/10.1038/s41588-020-00754-2 Diener, E., Lucas, R. E., &amp; Oishi, S. (2018). Advances and Open Questions in the Science of Subjective Well-Being. Collabra: Psychology, 4(1). https://doi.org/10.1525/collabra.115 Diener, E., Pressman, S. D., Hunter, J., &amp; Delgadillo-Chase, D. (2017). If, Why, and When Subjective Well-Being Influences Health, and Future Needed Research. Applied Psychology: Health and Well-Being, 9(2), 133–167. https://doi.org/10.1111/aphw.12090 Fredrickson, B. L., Tugade, M. M., Waugh, C. E., &amp; Larkin, G. R. (2003). What Good Are Positive Emotions in Crises? A Prospective Study of Resilience and Emotions Following the Terrorist attacks on the United States on September 11th, 2001. Journal of Personality and Social Psychology, 84(2), 365. https://doi.org/10.1037/0022-3514.84.2.365 Galatzer-Levy, I. R., Huang, S. H., &amp; Bonanno, G. A. (2018). Trajectories of resilience and dysfunction following potential trauma: A review and statistical evaluation. Clinical Psychology Review, 63, 41–55. https://doi.org/10.1016/j.cpr.2018.05.008 Greenspoon, P. J., &amp; Saklofske, D. H. (2001). Toward an integration of subjective well-being and psychopathology. Social Indicators Research, 54(1), 81–108. https://doi.org/10.1023/A:1007219227883 Hu, T., Zhang, D., &amp; Wang, J. (2015). A meta-analysis of the trait resilience and mental health. Personality and Individual Differences, 76, 18–27. https://doi.org/10.1016/j.paid.2014.11.039 Rohrer, J. M., &amp; Lucas, R. E. (2020). Causal Effects of Well-Being on Health : It ’ s Complicated. https://doi.org/https://doi.org/10.31234/osf.io/wgbe4 Ryff, C. D. (1989). Happiness is everything, or is it? Explorations on the meaning of psychological well-being. Journal of Personality and Social Psychology, 57(6), 1069–1081. https://doi.org/10.1037/0022-3514.57.6.1069 Satici, S. A. (2016). Psychological vulnerability, resilience, and subjective well-being: The mediating role of hope. PERSONALITY AND INDIVIDUAL DIFFERENCES, 102, 68–73. https://doi.org/10.1016/j.paid.2016.06.057 Steptoe, A. (2019). Happiness and Health. Annual Review of Public Health, 40, 339–359. https://doi.org/10.1146/annurev-publhealth-040218-044150 Van der Werff, S. J. A., Pannekoek, J. N., Veer, I. M., van Tol, M. J., Aleman, A., Veltman, D. J., Zitman, F. G., Rombouts, S. A. R. B., Elzinga, B. M., &amp; van der Wee, N. J. A. (2013). Resilience to childhood maltreatment is associated with increased resting-state functional connectivity of the salience network with the lingual gyrus. Child Abuse and Neglect. https://doi.org/10.1016/j.chiabu.2013.07.008 van Harmelen, A.-L., Blakemore, S. J., Goodyer, I. M., &amp; Kievit, R. A. (2020). The Interplay Between Adolescent Friendship Quality and Resilient Functioning Following Childhood and Adolescent Adversity. Adversity and Resilience Science. https://doi.org/10.1007/s42844-020-00027-1 World Health Organization. (2005). Promoting Mental Health: Concepts, Emerging Evidence, Practice. Zaninotto, P., &amp; Steptoe, A. (2019). English Longitudinal Study of Ageing. Encyclopedia of Gerontology and Population Aging. Cham: Springer International Publishing, 1–7. https://doi.org/10.1007/978-3-319-69892-2_335-

The association between parental internalizing disorders and child school performance

Abstract Parents play a crucial role in children’s lives. Despite high prevalences of anxiety and depression, we do not know how these disorders among parents associate with child school performance in Norway. We use regression models to estimate associations between parental mental disorders and child school performance, while adjusting for some social and genetic confounders. Parental anxiety and depression were assessed from administrative registers of government funded health service consultations for all individuals in Norway with children born between 1992 and 2002. School performance was assessed as standardized grade point average at the end of compulsory education when children are 16 years old. Associations were also considered in samples of adoptees and among differentially affected siblings. We find that 18.8% of children have a parent with an anxiety or depression diagnosis from primary care during the last three years of compulsory education (yearly prevalence: 11.5%). There is a negative association between these parental mental disorders and child school outcomes (z = 0.43). This association was weakened, but statistically significant among differentially exposed siblings (z = 0.04), while disappearing in adoptee children. Many children experience that their parents have anxiety or depression and receive a diagnosis from primary care. On average, these children have lower school performance. The association is attenuated when comparing differentially exposed siblings and disappears in adoptee children. These results have a poor fit with the hypothesis that parental internalizing is an influential causal factor in determining children’s educational success