Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants.

We examined more than 97,000 families from four neurodevelopmental disease cohorts and the UK Biobank to identify phenotypic and genetic patterns in parents contributing to neurodevelopmental disease risk in children. We identified within- and cross-disorder correlations between six phenotypes in parents and children, such as obsessive-compulsive disorder (R = 0.32-0.38, p < 10-126). We also found that measures of sub-clinical autism features in parents are associated with several autism severity measures in children, including biparental mean Social Responsiveness Scale scores and proband Repetitive Behaviors Scale scores (regression coefficient = 0.14, p = 3.38 × 10-4). We further describe patterns of phenotypic similarity between spouses, where spouses show correlations for six neurological and psychiatric phenotypes, including a within-disorder correlation for depression (R = 0.24-0.68, p < 0.001) and a cross-disorder correlation between anxiety and bipolar disorder (R = 0.09-0.22, p < 10-92). Using a simulated population, we also found that assortative mating can lead to increases in disease liability over generations and the appearance of "genetic anticipation" in families carrying rare variants. We identified several families in a neurodevelopmental disease cohort where the proband inherited multiple rare variants in disease-associated genes from each of their affected parents. We further identified parental relatedness as a risk factor for neurodevelopmental disorders through its inverse relationship with variant pathogenicity and propose that parental relatedness modulates disease risk by increasing genome-wide homozygosity in children (R = 0.05-0.26, p < 0.05). Our results highlight the utility of assessing parent phenotypes and genotypes toward predicting features in children who carry rare variably expressive variants and implicate assortative mating as a risk factor for increased disease severity in these families.

The inheritance of social status: England, 1600 to 2022.

A lineage of 422,374 English people (1600 to 2022) contains correlations in social outcomes among relatives as distant as 4th cousins. These correlations show striking patterns. The first is the strong persistence of social status across family trees. Correlations decline by a factor of only 0.79 across each generation. Even fourth cousins, with a common ancestor only five generations earlier, show significant status correlations. The second remarkable feature is that the decline in correlation with genetic distance in the lineage is unchanged from 1600 to 2022. Vast social changes in England between 1600 and 2022 would have been expected to increase social mobility. Yet people in 2022 remain correlated in outcomes with their lineage relatives in exactly the same way as in preindustrial England. The third surprising feature is that the correlations parallel those of a simple model of additive genetic determination of status, with a genetic correlation in marriage of 0.57.

Simultaneous inference of parental admixture proportions and admixture times from unphased local ancestry calls.

Population genetic analyses of local ancestry tracts routinely assume that the ancestral admixture process is identical for both parents of an individual, an assumption that may be invalid when considering recent admixture. Here, we present Parental Admixture Proportion Inference (PAPI), a Bayesian tool for inferring the admixture proportions and admixture times for each parent of a single admixed individual. PAPI analyzes unphased local ancestry tracts and has two components: a binomial model that leverages genome-wide ancestry fractions to infer parental admixture proportions and a hidden Markov model (HMM) that infers admixture times from tract lengths. Crucially, the HMM accounts for unobserved within-ancestry recombination by approximating the pedigree crossover dynamics, enabling inference of parental admixture times. In simulations, we find that PAPI's admixture proportion estimates deviate from the truth by 0.047 on average, outperforming ANCESTOR and PedMix by 46.0% and 57.6%, respectively. Moreover, PAPI's admixture time estimates were strongly correlated with the truth (R=0.76) but have an average downward bias of 1.01 generations that is partly attributable to inaccuracies in local ancestry inference. As an illustration of its utility, we ran PAPI on African American genotypes from the PAGE study (N = 5,786) and found strong evidence of assortative mating by ancestry proportion: couples' ancestry proportions are highly correlated (R = 0.87) and are closer to each other than expected under random mating (p < 10-6). We anticipate that PAPI will be useful in studying the population dynamics of admixture and will also be of interest to individuals seeking to learn about their personal genealogies.

Assortative mating on blood type: Evidence from one million Chinese pregnancies.

Blood type is one of the most fundamental phenotypes in biological, medical, and psychological studies. Using a unique dataset of one million Chinese pregnancies, we find strong evidence from a group of statistical tests for assortative mating on blood type. After controlling for anthropometric and socioeconomic confounders, assortative mating remains robust.

Assortative mating enhances postzygotic barriers to gene flow via ancestry bundling.

Hybridization and subsequent genetic introgression are now known to be common features of the histories of many species, including our own. Following hybridization, selection often purges introgressed DNA genome-wide. While assortative mating can limit hybridization in the first place, it is also known to play an important role in postzygotic selection against hybrids and, thus, the purging of introgressed DNA. However, this role is usually thought of as a direct one: a tendency for mates to be conspecific reduces the sexual fitness of hybrids, reducing the transmission of introgressed ancestry. Here, we explore a second, indirect role of assortative mating as a postzygotic barrier to gene flow. Under assortative mating, parents covary in their ancestry, causing ancestry to be "bundled" in their offspring and later generations. This bundling effect increases ancestry variance in the population, enhancing the efficiency with which postzygotic selection purges introgressed DNA. Using whole-genome simulations, we show that the bundling effect can comprise a substantial portion of mate choice's overall effect as a postzygotic barrier to gene flow. We then derive a simple method for estimating the impact of the bundling effect from standard metrics of assortative mating. Applying this method to data from a diverse set of hybrid zones, we find that the bundling effect increases the purging of introgressed DNA by between 1.2-fold (in a baboon system with weak assortative mating) and 14-fold (in a swordtail system with strong assortative mating). Thus, assortative mating's bundling effect contributes substantially to the genetic isolation of species.

Genetic structure, UV-vision, wing coloration and size coincide with colour polymorphism in Fabriciana adippe butterflies.

Colour polymorphisms have long served as model systems in evolutionary studies and continue to inform about processes involved in the origin and dynamics of biodiversity. Modern sequencing tools allow for evaluating whether phenotypic differences between morphs reflect genetic differentiation rather than developmental plasticity, and for investigating whether polymorphisms represent intermediate stages of diversification towards speciation. We investigated phenotypic and genetic differentiation between two colour morphs of the butterfly Fabriciana adippe using a combination of ddRAD-sequencing and comparisons of body size, colour patterns and optical properties of bright wing spots. The silvery-spotted adippe form had larger and darker wings and reflected UV light, while the yellow cleodoxa form displayed more green scales and reflected very little UV, showcasing that they constitute distinct and alternative integrated phenotypes. Genomic analyses revealed genetic structuring according to source population, and to colour morph, suggesting that the phenotypic differentiation reflects evolutionary modifications. We report 17 outlier loci associated with colour morph, including ultraviolet-sensitive visual pigment (UVRh1), which is associated with intraspecific communication and mate choice in butterflies. Together with the demonstration that the wings of the adippe (but essentially not the cleodoxa) morph reflect UV light, that UV reflectance is higher in females than males and that morphs differ in wing size, this suggests that these colour morphs might represent genetically integrated phenotypes, possibly adapted to different microhabitats. We propose that non-random mating might contribute to the differentiation and maintenance of the polymorphism.

Unifying quantification methods for sexual selection and assortative mating using information theory.

Sexual selection plays a crucial role in modern evolutionary theory, offering valuable insight into evolutionary patterns and species diversity. Recently, a comprehensive definition of sexual selection has been proposed, defining it as any selection that arises from fitness differences associated with nonrandom success in the competition for access to gametes for fertilization. Previous research on discrete traits demonstrated that non-random mating can be effectively quantified using Jeffreys (or symmetrized Kullback-Leibler) divergence, capturing information acquired through mating influenced by mutual mating propensities instead of random occurrences. This novel theoretical framework allows for detecting and assessing the strength of sexual selection and assortative mating. In this study, we aim to achieve two primary objectives. Firstly, we demonstrate the seamless alignment of the previous theoretical development, rooted in information theory and mutual mating propensity, with the aforementioned definition of sexual selection. Secondly, we extend the theory to encompass quantitative traits. Our findings reveal that sexual selection and assortative mating can be quantified effectively for quantitative traits by measuring the information gain relative to the random mating pattern. The connection of the information indices of sexual selection with the classical measures of sexual selection is established. Additionally, if mating traits are normally distributed, the measure capturing the underlying information of assortative mating is a function of the square of the correlation coefficient, taking values within the non-negative real number set [0, +∞). It is worth noting that the same divergence measure captures information acquired through mating for both discrete and quantitative traits. This is interesting as it provides a common context and can help simplify the study of sexual selection patterns.

Genetic basis of STEM occupational choice and regional economic performance: a UK biobank genome-wide association study.

BACKGROUND: Science, technology, engineering, and mathematics (STEM) professionals are regarded as the highly skilled labor force that fosters economic productivity, enterprise innovation, and international competitiveness of a country. This study aims to understand the genetic predisposition to STEM occupations and investigate its associations with regional economic performance. We conducted a genome-wide association study on the occupational choice of STEM jobs based on a sample of 178,976 participants from the UK Biobank database. RESULTS: We identified two genetic loci significantly associated with participants' STEM job choices: rs10048736 on chromosome 2 and rs12903858 on chromosome 15. The SNP heritability of STEM occupations was estimated to be 4.2%. We also found phenotypic and genetic evidence of assortative mating in STEM occupations. At the local authority level, we found that the average polygenic score of STEM is significantly and robustly associated with several metrics of regional economic performance. CONCLUSIONS: The current study expands our knowledge of the genetic basis of occupational choice and potential regional disparities in socioeconomic developments.

Divergent warning patterns influence male and female mating behaviours in a tropical butterfly.

Traits under divergent ecological selection that also function during mating can be important in maintaining species boundaries. Few studies have considered mutual mate choice, where both males and females base mating decisions on the same trait. Wing colouration in Heliconius butterflies evolved as a warning signal but also functions as a mating cue. We investigated the contribution of visual preference to assortative mating in an aposematic butterfly Heliconius cydno in the context of reproductive isolation with its sympatric, visually distinct relative Heliconius melpomene. Heliconius cydno have conspicuous white bands on their forewings, whereas those of H. melpomene are red in colour. We predicted that both sexes of H. cydno contributed to assortative mating by exhibiting visual preference towards conspecific wing colouration. We analysed published and new data from preference experiments, in which males were presented with conspecific and H. melpomene females. We also recorded female responses and mating outcomes in choice experiments, involving conspecific males with either the original white or artificially painted red forewing bands. Both sexes of H. cydno responded more positively towards the conspecific colouration, and males strongly preferred females of its own colours. In contrast, male colouration did not predict mating outcomes in female choice experiments. As courtships are initiated by males in butterflies, our findings suggest that female visual preference might be of secondary importance in H. cydno. Our data also suggest that the contribution of visual preference to reproductive isolation might be unequal between H. cydno and its sympatric relative H. melpomene.

Eight Decades of Educational Assortative Mating: A Research Note.

Recent social and economic trends in the United States, including increasing economic inequality, women's growing educational advantage, and the rise of online dating, have ambiguous implications for patterns of educational homogamy. In this research note, we examine changes in educational assortative mating in the United States over the last eight decades (1940 to 2020) using the U.S. decennial censuses and the American Community Survey, extending and expanding earlier work by Schwartz and Mare. We find that the rise in educational homogamy noted by Schwartz and Mare has not continued. Increases in educational homogamy stalled around 1990 and began reversing in the 2000s. We find a growing tendency for marriages to cross educational boundaries, but a college degree remains the strongest dividing line to intermarriage. A key trend explaining this new pattern is women's increasing tendency to marry men with less education than themselves. If not for this trend, homogamy would have continued increasing until the early 2010s. We also show substantial heterogeneity by race, ethnicity, and nativity and among same- versus different-sex couples.

rBahadur: efficient simulation of structured high-dimensional genotype data with applications to assortative mating.

Existing methods for generating synthetic genotype data are ill-suited for replicating the effects of assortative mating (AM). We propose rb_dplr, a novel and computationally efficient algorithm for generating high-dimensional binary random variates that effectively recapitulates AM-induced genetic architectures using the Bahadur order-2 approximation of the multivariate Bernoulli distribution. The rBahadur R library is available through the Comprehensive R Archive Network at https://CRAN.R-project.org/package=rBahadur .

Antagonistic Effects of Assortative Mating on the Evolution of Phenotypic Plasticity along Environmental Gradients.

AbstractPrevious theory has shown that assortative mating for plastic traits can maintain genetic divergence across environmental gradients despite high gene flow. Yet these models did not examine how assortative mating affects the evolution of plasticity. We here describe patterns of genetic variation across elevation for plasticity in a trait under assortative mating, using multiple-year observations of budburst date in a common garden of sessile oaks. Despite high gene flow, we found significant spatial genetic divergence for the intercept, but not for the slope, of reaction norms to temperature. We then used individual-based simulations, where both the slope and the intercept of the reaction norm evolve, to examine how assortative mating affects the evolution of plasticity, varying the intensity and distance of gene flow. Our model predicts the evolution of either suboptimal plasticity (reaction norms with a slope shallower than optimal) or hyperplasticity (slopes steeper than optimal) in the presence of assortative mating when optimal plasticity would evolve under random mating. Furthermore, a cogradient pattern of genetic divergence for the intercept of the reaction norm (where plastic and genetic effects are in the same direction) always evolves in simulations with assortative mating, consistent with our observations in the studied oak populations.

What's in a mate? Social pairing decisions and spatial cognitive ability in food-caching mountain chickadees.

While researchers have investigated mating decisions for decades, gaps remain in our understanding of how behaviour influences social mate choice. We compared spatial cognitive performance and food caching propensity within social pairs of mountain chickadees inhabiting differentially harsh winter climates to understand how these measures contribute to social mate choice. Chickadees rely on specialized spatial cognitive abilities to recover food stores and survive harsh winters, and females can discriminate among males with varying spatial cognition. Because spatial cognition and caching propensity are critical for survival and likely heritable, pairing with a mate with such enhanced traits may provide indirect benefits to offspring. Comparing the behaviour of social mates, we found that spatial cognitive performance approached a significant correlation within pairs at low, but not at high elevation. We found no correlation within pairs in spatial reversal cognitive performance at either elevation; however, females at high elevation tended to perform better than their social mates. Finally, we found that caching propensity correlated within pairs at low, while males cached significantly more food than their social mates at high elevations. These results suggest that cognition and caching propensity may influence social mating decisions, but only in certain environments and for some aspects of cognition.

Paternity data reveal high MHC diversity among sires in a polygynandrous, egalitarian primate.

Evidence from human and nonhuman primates suggests that females avoid breeding with close kin and may choose mates based on MHC diversity, which can improve offspring survival. In despotic societies, female mate choice may be hindered by male sexual coercion, but in egalitarian societies, females may be less constrained. Among northern muriquis-an egalitarian, polygynandrous primate with male philopatry-analyses of new data on paternity and variation at microsatellite and MHC loci, combined with behavioural and life-history data, revealed that sires showed higher MHC diversity than expected by chance and were never close kin of dams, consistent with predictions of female mate choice and close inbreeding avoidance. However, females did not differentially reproduce with males who were more distantly related to them or more dissimilar at the MHC than expected by chance, nor with those who had more MHC alleles distinct from their own. The lack of male dominance may permit females to identify and reproduce preferentially with non-offspring males and with males who are more diverse at the MHC. Nonetheless, the absence of disassortative mating at the MHC and neutral loci suggests that female mate choice may be limited by other factors impacting male fertilization success.

One versus two biological parents with mental disorders: Relationship to educational attainment in the next generation.

BACKGROUND: Both maternal and, separately, paternal mental illness are associated with diminished academic attainment among children. However, the differential impacts of diagnostic type and degree of parental burden (e.g. one v. both parents affected) on these functional outcomes are unknown. METHODS: Using the Swedish national patient (NPR) and multi-generation (MGR) registers, 2 226 451 children (1 290 157 parental pairs), born 1 January 1973-31 December 1997, were followed through 31 December 2013. Diagnostic status of all cohort members was defined for eleven psychiatric disorders, and families classed by exposure: (1) parents affected with any disorder, (2) parents affected with a disorder group (e.g. neuropsychiatric disorders), and (3) parents affected with a specific disorder (e.g. ADHD). Pairs were further defined as 'unaffected,' 'single-affected,', or 'dual-affected.' Among offspring, the study evaluated fulfillment of four academic milestones, from compulsory (primary) school through University (college). Sensitivity analyses considered the impact of child's own mental health, as well as parental education, on main effects. RESULTS: Marked reductions in the odds of achievement were observed, emerging at the earliest levels of schooling for both single-affected [adjusted odds ratio (aOR), 0.50; 95% CI 0.49-0.51] and dual-affected (aOR 0.29, 95% CI 0.28-0.30) pairs and persisting thereafter [aOR range (single), 0.52-0.65; aOR range (dual), 0.30-0.40]. This pattern was repeated for analyses within diagnosis/diagnostic group. Main results were robust to adjustment for offspring mental health and parent education level. CONCLUSIONS: Parental mental illness is associated with profound reductions in educational attainment in the subsequent generation, with children from dual-affected families at uniquely high risk.

Coming of age in your local mating market: Just a numbers game?

Research Highlight: Woodman, J. P., Cole, E. F., Firth, J. A., Perrins, C. M., & Sheldon, B. C. (2022). Disentangling the causes of age-assortative mating in bird populations with contrasting life-history strategies. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.13851. In their study of age-assortative mating, Woodman and colleagues thoroughly and concisely detail its behavioural determinants using datasets, astonishing in themselves, amassed from their decades-long studies of mute swans (Cygnus olor) and great tits (Parus major), species that are respectively longer- and shorter-lived and occupying different segments of the slow/fast life-history continuum. Here, they show that positive age-assortative mating occurs through active, age-based mate selection in mute swans which play the long game, whereas in the shorter-lived great tit this is principally a passive byproduct of demographic processes. That great tits have relatively lower interannual survivorship means that newly recruited, young birds occupy a larger proportion of the breeding population in any given year than occurs in mute swans. The adaptive significance of age-assortative mating is yet to be determined, but the current study provides an exciting possibility for the role of selection on assortative mating generally in either promoting or constraining active mate selection and sexual dimorphism within and across the tree of life.

Disentangling the causes of age-assortative mating in bird populations with contrasting life-history strategies.

Age shapes fundamental processes related to behaviour, survival and reproduction, where age influences reproductive success, non-random mating with respect to age can magnify or mitigate such effects. Consequently, the correlation in partners' age across a population may influence its productivity. Despite widespread evidence for age-assortative mating, little is known about what drives this assortment and its variation. Specifically, the relative importance of active (same-age mate preference) and passive processes (assortment as a consequence of other spatial or temporal effects) in driving age assortment is not well understood. In this paper, we compare breeding data from a great tit and mute swan population (51- and 31-year datasets, respectively) to tease apart the contributions of pair retention, cohort age structure and active age-related mate selection to age assortment in species with contrasting life histories. Both species show age-assortative mating and variable assortment between years. However, we demonstrate that the drivers of age assortment differ between the species, as expected from their life histories and resultant demographic differences. In great tits, pair fidelity has a weak effect on age-assortative mating through pair retention; variation in age assortment is primarily driven by fluctuations in age structure from variable juvenile recruitment. Age-assortative mating is, therefore, largely passive, with no evidence consistent with active age-related mate selection. In mute swans, age assortment is partly explained by pair retention, but not population age structure, and evidence exists for active age-assortative pairing. This difference is likely to result from shorter life-spans in great tits compared with mute swans, leading to fundamental differences in their population age structure, whereby a larger proportion of great tit populations consist of a single age cohort. In mute swans, age-assortative pairing through mate selection may also be driven by greater age-dependent variation in fitness. The study highlights the importance of considering how different life histories and demographic differences arising from these affect population processes that appear congruent across species. We suggest that future research should focus on uncovering the proximate mechanisms that lead to variation in active age-assortative mate selection (as seen in mute swans); and the consequences of variation in age structure on the ecological and social functioning of wild populations.

Prudent burrow-site selection in a landscape of fear.

Prey should select safer breeding sites over riskier sites of otherwise similar habitats. This preference, however, may differ between conspecifics of different competitive abilities if the costs of intraspecific competition overpower the benefits of breeding in a safer site. Our goal was to test this hypothesis by exploring the burrow-site selection of different-sized desert isopods (Hemilepistus reaumuri) near and away from a scorpion burrow. We found that larger females are more likely to occupy burrows than smaller females, regardless of whether these burrows were close or away from scorpion burrows. We also found that larger females stayed longer in safer burrows and that smaller females tended to stay longer in riskier sites even in the absence of direct competition, implying a prudent burrow-site selection. We found no association between male size and the tendency to occupy or to spend time in a burrow, regardless of whether these burrows were close or away from scorpion burrows. Our work highlights the need to consider intraspecific competition when exploring how predators regulate prey behaviour.

Racial/Ethnic Variation in the Relationship Between Educational Assortative Mating and Wives' Income Trajectories.

Prior work has examined the relationship between educational assortative mating and wives' labor market participation but has not assessed how this relationship varies by race/ethnicity. Using data from the National Longitudinal Survey of Youth 1979, we estimate group-based developmental trajectories to investigate whether the association between educational assortative mating and wives' income trajectories varies by race/ethnicity. The presence, prevalence, and shapes of prototypical long-term income trajectories vary markedly across racial/ethnic groups. Whites are more likely than Blacks and Hispanics to follow income trajectories consistent with a traditional gender division of labor. The association between educational assortative mating is also stronger for Whites than for Blacks and Hispanics. White wives in educationally hypogamous unions make the greatest contribution to the couple's total income, followed by those in homogamous and hypergamous unions. Black and Hispanic wives in hypogamous unions are less likely than their peers in other unions to be secondary earners. These findings underscore the need for studies of the consequences of educational assortative mating to pay closer attention to heterogeneity across and within racial/ethnic groups.

Genetic nurturing, missing heritability, and causal analysis in genetic statistics.

Genetic nurturing, the effect of parents' genotypes on offspring phenotypes through parental phenotypic transmission, can be modeled in terms of gene-culture interactions. This paper first uses a simple one-locus, two-phenotype gene-culture cotransmission model to compute the effect of genetic nurturing in terms of regression of children's phenotypes on transmitted and nontransmitted alleles. With genetic nurturing, interpreting heritability and hence the meaning of "missing heritability" becomes problematic. Other factors, for example, population subdivision and assortative mating, generate similar signals to those of genetic nurturing, namely, correlation between parents' nontransmitted alleles and children's phenotypes. Corrections must be made for these to isolate the signal of genetic nurturing. Finally, a unified causal framework is constructed for genetic nurturing, population subdivision, and assortative mating. Causal and noncausal paths from transmitted and nontransmitted alleles to children's phenotypes are identified and investigated in the presence of genetic nurturing, population subdivision, and assortative mating. Using causal analysis, assumptions made in inferring direct and indirect effects are then clarified and evaluated in a broader causal context.