A moderate proportion of the variance in antisocial phenotypes is accounted for by genetic variation.Reference Polderman, Benyamin, De Leeuw, Sullivan, Van Bochoven and Visscher¹ Phenotypic indicators of externalising traits, moreover, are correlated with other forms of psychopathological behaviour.Reference Krueger, Hicks, Patrick, Carlson, Iacono and McGue² These findings suggest a general vulnerability underlying the spectrum of externalising disorders, one underpinned by pleiotropic genetic influences. With the proliferation of population-based samples containing measured genes, researchers have investigated possible molecular correlates of antisocial behaviours. Although some promising results emerged, so too did to the recognition of limitations.Reference Dick, Agrawal, Keller, Adkins, Aliev and Monroe^3, Reference Chabris, Lee, Cesarini, Benjamin and Laibson⁴ Chief among them included the use of underpowered designs, lack of reproducibility and an absence of correction for multiple testing bias.Reference Chabris, Lee, Cesarini, Benjamin and Laibson⁴

As a result, studies utilising genome-wide techniques in large samples have become the preferred approach to unravelling the genetic architectures of complex traits (which have previously been shown to be moderately heritable).Reference Chabris, Lee, Cesarini, Benjamin and Laibson^4–Reference Pappa, St Pourcain, Benke, Cavadino, Hakulinen and Nivard¹⁰ Recent genome-wide association studies (GWAS) of antisocial phenotypes revealed a number of trait-relevant alleles that were nearly genome-wide significant.Reference Tielbeek, Johansson, Polderman, Rautiainen, Jansen and Taylor^5, Reference Pappa, St Pourcain, Benke, Cavadino, Hakulinen and Nivard¹⁰ GWAS evidence has also revealed associations between a number of single nucleotide polymorphisms (SNPs) and phenotypes known to correlate with antisocial behaviours.Reference Barban, Jansen, De Vlaming, Vaez, Mandemakers and Tropf⁶ In particular, various indicators of reproductive behaviour, such as age at menarche, age at first sexual contact and number of sexual partners, have all been examined using genetically sensitive data, with results identifying a number of genome-wide significant SNPs.Reference Barban, Jansen, De Vlaming, Vaez, Mandemakers and Tropf⁶

What remains in need of further testing is whether the genetic underpinnings of antisocial behaviour covary with the genetic underpinnings of reproductive indicators. For this topic, in particular, prior theoretical work has suggested that some forms of antisocial behaviour may represent natural variation in broad reproductive strategies – captured broadly in the area of life history evolution – that have been shaped by natural selection over the course of human evolution.Reference Boutwell, Barnes, Beaver, Haynes, Nedelec and Gibson⁷ This line of reasoning makes the explicit prediction that reproductive and antisocial behaviour should be correlated at a phenotypic level, and perhaps at a genetic level, such that alleles associated with antisocial behaviour are also associated with higher reproductive output and more rapid physical maturation. Indeed, in an earlier GWAS study, we examined the genetic covariation of antisocial behaviour with a range of cognitive, psychiatric and reproductive outcomes, utilising overlapping data, and reported some suggestive genetic correlations with various reproductive traits.Reference Tielbeek, Johansson, Polderman, Rautiainen, Jansen and Taylor⁵

We combined GWAS data from the Broad Antisocial Behavior Consortium (BroadABC) with data from the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium.Reference Pappa, St Pourcain, Benke, Cavadino, Hakulinen and Nivard¹⁰ In total, we meta-analysed genotypic and phenotypic data from 31 968 individuals across 13 unique samples, making it the largest collective sample available to estimate the effects of genome-wide genetic variation on antisocial behaviour. In addition, summary statistics for seven relevant reproductive and longevity traits were obtained from large existing GWAS data-sets. This study explores the genome-wide genetic correlation between reproductive traits and antisocial behaviour. By examining the extent to which alleles associated with antisocial behaviour are related to alleles underpinning variation in reproductive outcomes, this study could provide a better understanding of why these traits tend to correlate at the phenotypic level.Reference Boutwell, Barnes, Beaver, Haynes, Nedelec and Gibson⁷

Results

First, we calculated the SNP-based heritability estimates of antisocial behaviour and the life history traits, after which the genetic correlations between the traits were computed. The estimated heritability for antisocial behaviour utilising linkage disequilibrium score regression was low at 2.9% (s.e. 1.5%). Substantially higher estimates of the SNP-based heritability of antisocial behaviour have been reported elsewhere, using genome-wide complex traits analyses (GCTA) tools. We identified four cohorts (including QIMR, ALSPAC and GENR samples) with antisocial behaviour measures that previously performed GCTA, resulting in a sample-size weighted h ² of 35% (Table 1). These GCTA estimates are based on more homogeneous individual cohorts yielding smaller samples, which might explain the discrepancy in h ². The SNP heritabilities based on linkage disequilibrium score regression were 5.9% (s.e. 2.7%) and 5.2% (s.e. 2.7%), respectively, for the EAGLE and BroadABC consortia. Another possibility is that linkage disequilibrium score regression is more sensitive to causal SNPs being in low linkage disequilibrium with their neighbours.Reference Willer, Li and Abecasis¹²

Table 1 Previously reported genome-wide complex trait analysis estimates on antisocial behaviour

a. Estimates included above were derived from studies by Tielbeek et al (2012).Reference Tielbeek, Medland, Benyamin, Byrne, Heath and Madden¹¹

b. Estimates included above were derived from studies by Pappa et al (2016).Reference Pappa, St Pourcain, Benke, Cavadino, Hakulinen and Nivard¹⁰

c. SNP h ² is the estimation of narrow-sense heritability contributed by common SNPs. SNP, single nucleotide polymorphism; s.e., standard error

Our main analysis (Table 2, Fig. 1) revealed significant (α < 0.0071) genetic correlations of antisocial behaviour with age at first birth (r _g = −0.64, P = 0.0008) and number of children ever born (r _g = 0.50, P = 0.0065), as well as suggestive associations with parents', mothers' and fathers' age at death, but not with age at menarche or age at menopause (r_g = 0.026, P = 0.76 and r _g = −0.10, P = 0.48, respectively). Moreover, sign tests revealed fewer SNPs yielding a P-value < 0.05 with the same direction of effect than expected by chance (proportion 0.47, P < 0.001) for antisocial behaviour and age at first birth.

Fig. 1 Genetic correlations between antisocial behaviour and life history variables.

Table 2 Genetic correlations across life history speed indicators (four reproductive traits and three longevity traits) and broad antisocial behaviour

Genome-wide association study summary statistics from our combined analyses were used to calculate the r _g values with other traits. Single nucleotide polymorphism (SNP) h ² is the estimation of narrow-sense heritability contributed by common SNPs. r _g is the genetic correlation and is calculated with the LDSC software package, using pre-calculated linkage disequilibrium scores from Bulik-Sullivan et al.Reference Bulik-Sullivan, Loh, Finucane, Ripke, Yang and Patterson⁸

* Nominally significant (P < 0.05), ** Significant at the multiple-testing corrected P-value (0.0071).