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Unravelling the genetic influences of reproductive behaviour and gene-environment interaction

Final Report Summary - SOCIOGENOME (Unravelling the genetic influences of reproductive behaviour and gene-environment interaction)

SOCIOGENOME was the first to engage in a study of genetic discovery and examination of the role of genes and gene-environment (GxE) interaction in relation to human reproductive behaviour – age at first birth and number of children ever born. Whereas the social sciences focussed on how choice, individual, social, cultural and institutional factors influenced reproductive behaviour, for the first time in history we were able to demonstrate that there is a genetic component to reproductive behaviour. We made several fundamentally new discoveries, empirically demonstrating that reproductive behaviour had a genetic component, with prediction nearing classic social science variables. We also explained some of the biological underpinnings of these genetic loci. We likewise revealed that genetic predispositions are influenced by the socio-environment and are not easily separated, with contemporary complex polygenic scores picking up socio-environmental influences. Lead by PI Melinda Mills, the team included the dedicated group of Dr. Nicola Barban, Dr. Felix Tropf, Dr. David Brazel, Dr. Xuejie Ding and Dr. Riley Taiji and PhD, Giacomo Arrighini. This transdisciplinary and high-risk project produced over 40 high-level publications in a variety of disciplines including top journals in the: general sciences (Science, PNAS, Nature Human Behavior), genetics (Nature Genetics, European Journal of Human Genetics), sociology (Annual Review of Sociology, American Sociological Review, European Sociological Review, JMF), demography (Demography, European Journal of Population), medical sciences and psychiatry (JAMA Psychiatry, Human Reproduction) and even biology (Proceedings of the Royal Society B: Biological Sciences, American Journal of Human Biology).

The project had four objectives to first, construct a multifactor theoretical and measurement model. This was achieved through various publications including Balbo et al. (2013), and Mills, Barban, Tropf (2020, MIT) with a milestone article outlining the new sub-discipline in the top sociology journal Annual Review of Sociology (Mills & Tropf 2020). A second objective was to develop measures for the genetic and socio-environment factors related to reproductive behaviour. This was achieved throughout with one landmark paper in Nature Human Behavior study that demonstrated heterogeneity in genetic effects across historical birth cohorts and country using real data and a series of simulations (Tropf et al. 2017). We also used novel genomic techniques. We applied genome-restricted maximum likelihood estimation (GREML) to show for the first time that reproductive behaviour had a genetic component (SNP-heritability) of 10-15% (Tropf et al. 2015). Other milestones included several genome-wide association studies (GWASs). In our initial study (Barban et al. 2016) published in Nature Genetics, we uncovered 12 loci related to reproductive behaviour, which was extended in two studies forthcoming in 2020 revealing almost 400 loci and predicting up to 6% of the variance. Critical invited commentaries also appeared in key science journals (e.g. Mills 2019 in Science, Courtiol, Tropf & Mills 2016 in PNAS). The third objective aimed at partitioning the variance explained by genetic and socio-environmental factors and the role of gene-environment (GxE) interaction, which was realized in numerous publications applying our GWAS results. The fourth objective aimed to identify causal mechanisms and applied bi-directional Mendelian Randomization and Genomic Structural Equation Modelling. A series of publications revealed a complex web of overlapping traits measuring a common factor, often confounded by socioeconomic status. Three new objectives that emerged were: (1) a 450 page textbook describing our innovative methodological approach (Mills et al. 2020, MIT), (2) online tool to create awareness about diversity in genomic research (Mills & Rahal 2019; 2020, Nature Genetics); and, (3) bringing a social science perspective into genetics. Knowledge transfer to non-scientific audiences was immense with clear strategies (e.g. social media, multilingual press releases and FAQs, films and blogs) resulting in extensive media coverage.