Level Of Theory Research Articles

Local genetic correlation via knockoffs reduces confounding due to cross-trait assortative mating.

Local genetic correlation analysis is an important tool for identifying genetic loci with shared biology across traits. Recently, Border etal. have shown that the results of these analyses are confounded by cross-trait assortative mating (xAM), leading to many false-positive findings. Here, we describe LAVA-Knock, a local genetic correlation method that builds off an existing genetic correlation method, LAVA, and augments it by generating synthetic data in a way that preserves local and long-range linkage disequilibrium (LD), allowing us to reduce the confounding induced by xAM. We show in simulations based on a realistic xAM model and in genome-wide association study (GWAS) applications for 630 trait pairs that LAVA-Knock can greatly reduce the bias due to xAM relative to LAVA. Furthermore, we show a significant positive correlation between the reduction in local genetic correlations and estimates in the literature of cross-mate phenotype correlations; in particular, pairs of traits that are known to have high cross-mate phenotype correlation values have a significantly higher reduction in the number of local genetic correlations compared with other trait pairs. A few representative examples include education and intelligence, education and alcohol consumption, and attention-deficit hyperactivity disorder and depression. These results suggest that LAVA-Knock can reduce confounding due to both short-range LD and long-range LD induced by xAM.

Responses in adult pied flycatcher males depend on playback song similarity to local population

Abstract Song divergence driven by social learning has been proposed to be a key factor driving allopatric speciation in oscine birds. Songbirds often respond more to songs deriving from their local population, suggesting the potential for acoustic divergence across populations to shape both intra- and intersexual interactions. However, many of these studies were conducted on species with simple songs and, as a result, we know comparatively little about the emergence of population differences and song discrimination in species with complex songs. We addressed this question in the pied flycatcher (Ficedula hypoleuca) by calculating the dissimilarity of songs from two foreign populations as well as from our study site to the local centroid. We then conducted a paired-design playback experiment where both local and foreign songs were played simultaneously. We found that pied flycatcher males showed significantly stronger responses to those songs that sounded more similar to the local population. This suggests that despite the high complexity of the pied flycatcher song, individuals are still able to discriminate across populations. Our results support the hypothesis that learned song divergence can act as a mechanism for assortative mating and allopatric speciation.

Untangling the Role of Assortative Mating in Educational Reproduction in Twelve European Countries

In this study, we explore how educational differences in demographic behavior – in particular, mating patterns and fertility – mediate the intergenerational reproduction of educational inequality in twelve European countries. Although this research interest itself is not new, we contribute to this debate by adopting a prospective approach and scaling it to include multiple countries and cohorts. To this end, we leverage a series of complementary datasets and the inferential method developed by Song and Mare (2015) and advanced by Skopek and Leopold (2020) to estimate the components of a stylized educational reproduction model. We then employ a simple decomposition analysis to quantify the contributions of different pathways to prospective educational reproduction rates across educational backgrounds and explore the differences across cohorts and countries. We report several findings. Most notably, (1) the intergenerational reproduction of educational inequality persists in all twelve countries and is barely offset by small (and declining) negative educational gradients in fertility, (2) educational differences in selection into partnership are small and do not account for much inequality, and (3) the role of assortative mating, where present, is ambiguous because it both reinforces inequality via its effects on resources within the family and offsets it via its effects on fertility. * This article belongs to a special issue on “Changes in Educational Homogamy and Its Consequences”.

Who dominates? Multiple constructions of women's subjective social status and their cohort dynamics in transitional China

The way women construct their subjective social status has garnered significant attention. However, the roles of husbands and fathers in this process have been underexplored, with even less focus on how these roles have evolved across generations. This study aims to answer two important questions against the backdrop: First, which is the most dominant factor in shaping married women's subjective social status, their own objective class or those of their husband or father? Answers to this question reveal the impacts of assortative mating and intergenerational mobility. Second, how does the construction pattern change across birth cohorts? Cohort dynamics help reflect the evolution of gender roles and family values in China. Using pooled data from the Chinese General Social Survey in 2010–2017 and the diagonal reference model, our study finds that Chinese married women previously tended to construct their own social status based on the objective class of their husbands. However, this trend is reversed for younger cohorts. Father's objective class status carries roughly the same weight as women's own, but its impact becomes moderately stronger in younger cohorts. Taken together, the above findings reveal a unique pathway of family modernization in transitional China. Married women, although increasingly independent of their spouses, still remain closely connected with their natal families.

Estimation of Direct and Indirect Polygenic Effects and Gene-Environment Interactions using Polygenic Scores in Case-Parent Trio Studies.

Family-based studies provide a unique opportunity to characterize genetic risks of diseases in the presence of population structure, assortative mating, and indirect genetic effects. We propose a novel framework, PGS-TRI, for the analysis of polygenic scores (PGS) in case-parent trio studies for estimation of the risk of an index condition associated with direct effects of inherited PGS, indirect effects of parental PGS, and gene-environment interactions. Extensive simulation studies demonstrate the robustness of PGS-TRI in the presence of complex population structure and assortative mating compared to alternative methods. We apply PGS-TRI to multi-ancestry trio studies of autism spectrum disorders (N trio = 1,517) and orofacial clefts (N trio = 1,904) to establish the first transmission-based estimates of risk associated with pre-defined PGS for these conditions and other related traits. For both conditions, we further explored offspring risk associated with polygenic gene-environment interactions, and direct and indirect effects of genetically predicted levels of gene expression and metabolite traits.

Sex-specific expression of circadian rhythms enables allochronic speciation

Abstract Noctuid moths provide prime examples of species in various stages of allochronic speciation, where reproductive barriers are mediated by genetic divergence in daily or seasonal timing. Theory indicates that allochronic divergence might be one of the most plausible mechanisms of adaptive speciation, especially when timing is subject to divergent ecological selection. Here, we show that the validity of this theoretical expectation is entirely contingent on species characteristics of the mating system. Our analysis focuses on the moth Spodoptera frugiperda (Lepidoptera, Noctuidae), which occurs as two strains that differ in circadian reproductive activity. Unlike in generic models of assortative mating, where chronotypes diverge under mild assumptions, individual-based evolutionary simulations of the mating system and life cycle of S. frugiperda fail to recover allochronic diversification, even under conditions highly conducive to speciation. Instead, we observe that both chronotypes advance their activity schedule toward the early night, resulting in a rapid loss of allochronic variation. This outcome is caused by the fact that mating in S. frugiperda takes considerable time and potential mates are encountered sequentially, so that early males enjoy a systematic advantage. The undermining effect of male mate competition can be overcome when circadian genes evolve sex-specific expression, enabling early and late chronotypes to be maintained or even to diversify in sympatry. These results give new significance to sex differences in biological rhythms and suggest that species characteristics of the mating system and genetic architecture are key to understanding the scope for allochronic speciation across diverse species exhibiting variation in timing.

Reconciling Santa Rosalia: Both Reproductive Isolation and Coexistence Constrain Diversification.

AbstractUnderstanding patterns of diversification necessarily requires accounting for both the generation and the persistence of species. Formal models of speciation genetics, however, focus on the generation of new species without explicitly considering the maintenance of biodiversity (e.g., coexistence, the focus of ecological studies of diversity). Consequently, it remains unclear whether and how new species will coexist following a speciation event, a gap limiting our ability to understand the rate-limiting controls of diversification over macroevolutionary timescales. To connect coexistence and speciation theory and assess the relative importance of ecological versus genetic constraints in diversification events, we develop a deterministic, three-locus, population-genetic model that includes a skewed distribution of available resources (to generate variation in fitness differences), frequency-dependent competition, and assortative mating. Both ecology and genetics play vital and interacting roles in shaping initial speciation events and long-term eco-evolutionary outcomes. Ecological constraints are especially important when fitness differences are large and competition remains strong among dissimilar phenotypes. Ephemeral species can occur in our model and are typically lost because of competitive exclusion, a result demonstrating that species persistence may serve as the rate-limiting control of long-term diversification rates. More broadly, our model adds evidence that the unification of ecological and evolutionary (including genetic) perspectives on biodiversity is needed to predict large-scale patterns.

Partners’ Age Difference and Marital Dissolution in Italy. A Cohort Comparison

Among the factors related to marital disruption, age assortative mating (who marries whom in terms of age) has received less attention than others. In this study, we study the association between partners’ age difference and marital disruption in Italy, a late-comer country in divorce legislation and highly conservative in its culture and institutions. We also show how this association varies across marriage cohorts. We employ data from “Families, social subjects and life cycle” (FSS), collected in 2016 by the Italian National Institute of Statistics (Istat). We analyse micro-level retrospective information on first-marriage histories between the 1970s and the 1990s through an event-history approach. Results show that age hypogamous couples (where the woman is older than the man) have a higher likelihood of marital disruption compared to couples where the wife is the same age or younger than her husband. However, this higher risk reduces among the youngest cohorts. We discuss the possible drivers of this change in light of cultural changes that occurred in recent decades. * This article belongs to a special issue on “Changes in Educational Homogamy and Its Consequences”.

Concentration of disability in families: Intergenerational transmission or assortative mating?

Although studies have established that health and socioeconomic disadvantages often accumulate within families, little is known about the extent to which disability is concentrated within certain families and transmitted across generations. We use retrospective information about growing up with parent(s) or sibling(s) with a disability from the 2020 wave of the representative Survey of Health, Impairment and Living Conditions in Denmark (N = 7709). Building on this data and applying a family life course perspective, we examine if growing up with parent(s) and/or sibling(s) with a disability is associated with 1) having a disability oneself, 2) the probability of having a partner with a disability and 3) the occurrence of disability in the next generation. Our findings demonstrate that the odds of having a disability are higher among individuals who grew up with parent(s) and/or sibling(s) with a disability. While the odds of being partnered are not associated with family members’ disabilities, we find a positive association between having grown up with parents with a disability and having a partner with a disability. Moreover, having a child with a disability is positively associated with one’s own, parents’, siblings’ and partner’s disabilities. We thus conclude that disability is concentrated within certain families and that both intergenerational transmission and assortative mating contribute to this concentration.

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.

Assortative mating across nine psychiatric disorders is consistent and persistent over cultures and generations.

Emerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders. Here, using national registry datasets, we conduct the largest scale of AM analyses on nine psychiatric disorders, with up to 1.4 million mated cases and 6 million matched controls. We performed meta-analyses on AM estimates from Taiwan, Denmark, and Sweden, to examine the potential impact of cultural differences. Generational changes for people born after 1930s were investigated as well. We found that AM of psychiatric disorders are consistent across nations and persistent over generations, with a small proportion of disorders showing generational changes of AM. Our results provide additional insight into the mechanisms of AM across psychiatric disorders and have evident implications on the estimation of the genetic architectures of psychiatric disorders.

Form-assortative mating behaviors of individuals from parasitic and non-parasitic populations of Arctic lamprey (Lethenteron camtschaticum)

Abstract Evolutionary theory predicts that assortative mating is crucial for sympatric speciation by generating reproductive isolation between diverging populations. Here, we investigate the potential of form-assortative mating, an assumed mating pattern in lampreys, for sympatric speciation. By continuously recording mating activity between anadromous and freshwater-resident forms of L. camtschaticum that greatly differ in body size, we show that lampreys tend to mate with individuals of similar size in experimental conditions. However, we highlight that this pattern does not result from a choice of same-form partner but is the result of the simultaneous action of a preference of males – whatever their size – for large anadromous females, a higher competitive ability of aggressive males and physical constraints on heteroform pairs. Moreover, we do not advocate that sympatric speciation, as the sole consequence of form-assortative mating through sexual selection, is a plausible mechanism for the diversification of lampreys as a significant number of sneaking behaviors were observed in freshwater-resident males toward large anadromous females. Broader attention should be given to mechanisms other than sexual selection that may lead to form-assortative mating, such as variations in spatial or temporal distribution of alternative forms during reproductive season.

Assortativity in sympatric speciation and species classification

We investigate the role of assortative mating in speciation using the sympatric model of Derrida and Higgs. The model explores the idea that genetic differences create incompatibilities between individuals, preventing mating if the number of such differences is too large. Speciation, however, only happens in this mating system if the number of genes is large. Here we show that speciation with small genome sizes can occur if assortative mating is introduced. In our model individuals are represented by three chromosomes: one responsible for reproductive compatibility, one for coding the trait on which assortativity will operate, and a neutral chromosome. Reproduction is possible if individuals are genetically similar with respect to the first chromosome, but among these compatible mating partners, the one with the most similar trait coded by the second chromosome is selected. We show that this type of assortativity facilitates speciation, which can happen with a small number of genes in the first chromosome. Species, classified according to reproductive isolation, dictated by the first chromosome, can display different traits values, as measured by the second and the third chromosomes. Therefore, species can also be identified based on similarity of the neutral trait, which works as a proxy for reproductive isolation.

A Phenome-Wide Association Study (PheWAS) of Genetic Risk for C-Reactive Protein in Children of European Ancestry: Results From the ABCD Study.

C-reactive protein (CRP) is a moderately heritable marker of systemic inflammation that is associated with adverse physical and mental health outcomes. Identifying factors associated with genetic liability to elevated CRP in childhood may inform our understanding of variability in CRP that could be targeted to prevent and/or delay the onset of related health outcomes. We conducted a phenome-wide association study (PheWAS) of genetic risk for elevated CRP (i.e. CRP polygenic risk score [PRS]) among children genetically similar to European ancestry reference populations (median analytic n = 5,509) from the Adolescent Brain and Cognitive Development℠ (ABCD) Study. Associations between CRP PRS and 2,377 psychosocial and neuroimaging phenotypes were estimated using independent mixed effects models. Post hoc analyses examined whether: (1) covarying for measured body mass index (BMI) or removing the shared genetic architecture between CRP and BMI altered phenotypic associations, (2) sex moderated CRP PRS associations, and (3) associations are unconfounded by assortative mating or passive gene-environment correlations (using a within-family analyses). Multiple testing was adjusted for using Bonferroni and false discovery rate (FDR) correction. Nine phenotypes were positively associated with CRP PRS after multiple testing correction: five weight- and eating-related phenotypes (e.g. BMI, overeating), three phenotypes related to caregiver somatic problems (e.g. caregiver somatic complaints), as well as weekday video watching (all ps = 1.2 × 10-7 - 2.5 × 10-4, all p FDR s = 0.0002 - 0.05). No neuroimaging phenotypes were associated with CRP PRS (all ps = 0.0003 - 0.998; all p FDR s = 0.08 - 0.998) after correction for multiple testing. Eating and weight-related phenotypes remained associated with CRP PRS in within-family analyses. Covarying for BMI resulted in largely consistent results, and sex did not moderate any CRP PRS associations. Removing the shared genetic variance between CRP and BMI attenuated all relationships; associations with weekday video watching, caregiver somatic problems and caregiver report that the child is overweight remained significant while associations with waist circumference, weight, and caregiver report that child overeats did not. Genetic liability to elevated CRP is associated with higher weight, eating, and weekday video watching during childhood as well as caregiver somatic problems. These associations were consistent with direct genetic effects (i.e., not solely due to confounding factors like passive gene-environment correlations) and were independent of measured BMI. The majority of associations with weight and eating phenotypes were attributable to shared genetic architecture between BMI and inflammation. The relationship between genetics and heightened inflammation in later life may be partially attributable to modifiable behaviors (e.g. weight and activity levels) that are expressed as early as childhood.

Assortative mating and the dark triad: Evidence from the UK, Fiji, and meta-analytic review

The ‘dark triad’ represents the socially aversive personality traits of Machiavellianism, subclinical narcissism (henceforth, ‘narcissim’), and subclinical psychopathy (henceforth, ‘psychopathy’). There is evidence of assortative mating suggesting romantic partners are more similar than chance for these traits at the start of relationships (initial assortment) and not becoming alike with time (convergence), that people seek out partners to whom they are similar (active assortment), and that partner resemblance is not explained by social stratification processes (social homogamy). As the literature relates primarily to Eastern European and North American populations, we present studies from the UK (N = 104 couples) and Fiji (N = 99 couples). These showed significant positive assortment for each dark triad trait (other than psychopathy in the Fijian sample), and suggest the effects are explained by initial and active assortment and not by convergence or social homogamy. We also submitted the literature to meta-analytic review (Machiavellianism: k = 10, N = 1302; narcissism: k = 14, N = 1645; psychopathy: k = 13, N = 1989) and observed positive within-couple correlations of small (narcissism, psychopathy) to medium (Machiavellianism) effect size for each of the dark triad traits.

Interracial Unions and Racial Assortative Mating in an Age of Growing Diversity, Shifting Intimate Relationships, and Emerging Technologies

While racial assortative mating and interracial unions have been a central interest in the study of race relations and family demography since the early twentieth century, there have been marked changes in the social contexts in which these processes have taken place in recent decades. This review article examines three important shifts: (a) the rise of population diversity and its impact on traditional views of racial integration, (b) the changing institution of marriage in American life, and (c) the increasing centrality of technology. We discuss how these societal shifts have challenged traditional understandings of preferences, opportunities, and intermediaries in the mate selection process, as well as new opportunities for interracial intimacy that these changes have introduced. We conclude with a discussion on conceptual issues and promising future research directions.

Educational attainment and mental health conditions: a within-sibship Mendelian randomization study.

Observational studies have demonstrated consistent protective effects of higher educational attainment (EA) on the risk of suffering mental health conditions (MHC). Determining whether these beneficial effects are causal is challenging given the potential role of dynastic effects and demographic factors (assortative mating and population structure) in this association. To evaluate to what extent the relationship between EA and various MHC is independent from dynastic effects and demographic factors. Within-sibship Mendelian randomization (MR) study. One-sample MR analyses included participants' data from the Trøndelag Health Study (HUNT, Norway) and UK Biobank (United Kingdom). For two-sample MR analyses we used summary statistics from publicly available genome-wide-association-studies. 61 880 siblings (27 507 sibships). Years of education. Scores for symptoms of anxiety, depression and neuroticism using the Hospital Anxiety Depression Scale (HADS), the 7-item Generalized Anxiety Disorder Scale (GAD-7), the 9-item Patient Health Questionnaire (PHQ-9), and the Eysenck Personality Questionnaire, as well as self-reported consumption of psychotropic medication. One standard deviation (SD) unit increase in years of education was associated with a lower symptom score of anxiety (-0.20 SD [95%CI: -0.26, -0.14]), depression (-0.11 SD [-0.43, 0.22]), neuroticism (-0.30 SD [-0.53, -0.06]), and lower odds of psychotropic medication consumption (OR: 0.60 [0.52, 0.69]). Estimates from the within-sibship MR analyses showed some attenuation, which however were suggestive of a causal association (anxiety: -0.17 SD [-0.33, -0.00]; depression: -0.18 SD [-1.26, 0.89]; neuroticism: -0.29 SD [-0.43, -0.15]); psychotropic medication consumption: OR, 0.52 [0.34, 0.82]). Associations between EA and MHC in adulthood, although to some extend explained by dynastic effects and demographic factors, overall remain robust, indicative of a causal effect. However, larger studies are warranted to improve statistical power and further validate our conclusions.

Interpreting SNP heritability in admixed populations.

SNP heritability is defined as the proportion of phenotypic variance explained by genotyped SNPs and is believed to be a lower bound of heritability ( ), being equal to it if all causal variants are known. Despite the simple intuition behind , its interpretation and equivalence to is unclear, particularly in the presence of population structure and assortative mating. It is well known that population structure can lead to inflation in estimates because of confounding due to linkage disequilibrium (LD) or shared environment. Here we use analytical theory and simulations to demonstrate that estimates can be biased in admixed populations, even in the absence of confounding and even if all causal variants are known. This is because admixture generates LD, which contributes to the genetic variance, and therefore to heritability. Genome-wide restricted maximum likelihood (GREML) does not capture this contribution leading to under- or over-estimates of relative to , depending on the genetic architecture. In contrast, Haseman-Elston (HE) regression exaggerates the LD contribution leading to biases in the opposite direction. For the same reason, GREML and HE estimates of local ancestry heritability are also biased. We describe this bias in and as a function of admixture history and the genetic architecture of the trait and show that it can be recovered under some conditions. We clarify the interpretation of in admixed populations and discuss its implication for genome-wide association studies and polygenic prediction.

The apple doesn't fall far from the tree: Intergenerational wealth mobility in Taiwan

We estimate intergenerational wealth mobility using administrative records from Taiwan and find strong intergenerational rank correlations in household gross wealth, around 0.40 for sons and 0.30 for daughters. The wealth rank correlations are similar for single and married children, even though married children have greater household wealth and relatively strong assortative mating. The intergenerational wealth correlation is nonlinear and particularly strong for families in the top 10 % of household wealth. Different family sizes and gender compositions do not significantly affect intergenerational wealth mobility, regardless of the children's gender or marital status. Since our sample includes only parents who are still alive, these correlations are not driven by bequests. However, inter vivos transfers appear to play a significant role.

Benchmarking Mendelian randomization methods for causal inference using genome-wide association study summary statistics

Mendelian randomization (MR), which utilizes genetic variants as instrumental variables (IVs), has gained popularity as a method for causal inference between phenotypes using genetic data. While efforts have been made to relax IV assumptions and develop new methods for causal inference in the presence of invalid IVs due to confounding, the reliability of MR methods in real-world applications remains uncertain. Instead of using simulated datasets, we conducted a benchmark study evaluating 16 two-sample summary-level MR methods using real-world genetic datasets to provide guidelines for the best practices. Our study focused on the following crucial aspects: type I error control in the presence of various confounding scenarios (e.g., population stratification, pleiotropy, and family-level confounders like assortative mating), the accuracy of causal effect estimates, replicability, and power. By comprehensively evaluating the performance of compared methods over one thousand exposure-outcome trait pairs, our study not only provides valuable insights into the performance and limitations of the compared methods but also offers practical guidance for researchers to choose appropriate MR methods for causal inference.