Systematic approaches to assessing high-temperature limits to fertility in animals.

Critical thermal limits (CTLs) gauge the physiological impact of temperature on survival or critical biological function, aiding predictions of species range shifts and climatic resilience. Two recent Drosophila species studies, using similar approaches to determine temperatures that induce sterility (thermal fertility limits [TFLs]), reveal that TFLs are often lower than CTLs and that TFLs better predict both current species distributions and extinction probability. Moreover, many studies show fertility is more sensitive at less extreme temperatures than survival (thermal sensitivity of fertility [TSF]). These results present a more pessimistic outlook on the consequences of climate change. However, unlike CTLs, TFL data are limited to Drosophila, and variability in TSF methods poses challenges in predicting species responses to increasing temperature. To address these data and methodological gaps, we propose 3 standardized approaches for assessing thermal impacts on fertility. We focus on adult obligate sexual terrestrial invertebrates but also provide modifications for other animal groups and life-history stages. We first outline a "gold-standard" protocol for determining TFLs, focussing on the effects of short-term heat shocks and simulating more frequent extreme heat events predicted by climate models. As this approach may be difficult to apply to some organisms, we then provide a standardized TSF protocol. Finally, we provide a framework to quantify fertility loss in response to extreme heat events in nature, given the limitations in laboratory approaches. Applying these standardized approaches across many taxa, similar to CTLs, will allow robust tests of the impact of fertility loss on species responses to increasing temperatures.

Virtually delivered cognitive behavioural therapy for avoidant restrictive food intake disorder (CBT-AR): a case study in an adult with elevated autistic traits.

Cognitive Behavioural Therapy for Avoidant and Restrictive Food Intake Disorder (CBT-AR; ARIFD) is a psychological treatment that targets many of the core symptoms of ARFID. Although a growing literature supports the efficacy of behavioural interventions for paediatric feeding and eating disorders, including ARFID, the applicability of these methods to adults remains undetermined. Telehealth delivery of CBT-AR in adults with autism has yet to be tested. With this study, we conduct a preliminary evaluation of CBT-AR delivered virtually to a 26-year-old white British female, with mixed ARFID and elevated autistic traits. She attended 23 remote CBT-AR sessions facilitated through a dedicated telehealth platform. Adjustments were made to accommodate her lived experience of neurodiversity. Using a pre-post treatment design, changes on measures of subjective goal attainment, eating-related and general psychosocial impairment, general anxiety, and depression were evaluated. Following treatment, the participant had made significant progress towards personally meaningful goals, with improvements observed in nutritional intake, general well-being, and reductions in eating-related psychosocial impairment and general anxiety. The results offer preliminary insights into acceptability and efficacy of virtual CBT-AR for neurodiverse individuals.

The United Kingdom Eating Disorders Genetics Initiative.

OBJECTIVE: The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide. This article serves the dual function of providing an in-depth description of our study protocol and of describing our initial sample including demographics, diagnoses, and physical and psychiatric comorbidities. METHOD: EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies. RESULTS: As of September 2022, EDGI UK recruited 7435 survey participants: 98% female, 93.1% white, 97.8% cisgender, 65.9% heterosexual, and 52.1% have a university degree. Over half (57.8%) of these participants have returned their saliva DNA kit. The most common diagnoses are anorexia nervosa (48.3%), purging disorder (37.8%), bulimia nervosa (37.5%), binge-eating disorder (15.8%), and atypical anorexia nervosa (7.8%). CONCLUSION: EDGI UK is the largest UK eating disorders study and efforts to increase its diversity are underway. It offers a unique opportunity to accelerate eating disorder research. Researchers and participants with lived experience can collaborate on projects with unparalleled sample size. PUBLIC SIGNIFICANCE STATEMENT: Eating disorders are debilitating and costly for society but are under-researched due to underfunding. EDGI UK is one of the largest eating disorder studies worldwide with ongoing recruitment. The collected data constitute a resource for secondary analysis. We will combine data from all international EDGI branches and the NIHR BioResource to facilitate research that improves our understanding of eating disorders and their comorbidities.

The effect of short-term exposure to high temperatures on male courtship behaviour and mating success in the fruit fly Drosophila virilis.

Human-induced climate change is leading to higher average global temperatures and increasingly extreme weather events. High temperatures can have obvious effects on animal survival, particularly in ectotherms. However, the temperature at which organisms become sterile may be significantly lower than the temperature at which other biological functions are impaired. In the fruit fly Drosophila virilis, males are sterilized at temperatures above 34 °C, but are still active and able to mate normally. We investigated the male behavioural changes associated with high-temperature fertility loss. We exposed males to a warming treatment of 34.4 °C or 36.6 °C for 4 h, and then recorded their mating behaviour after being allowed to recover for 24 h. Previous work in this species suggests that males exposed to 34.4 °C lose the ability to produce new sperm, but can utilize mature sperm produced before the heat shock. We therefore predicted that these males would increases their courtship rate, and reduce their choosiness, in order to try to ensure a mating before their remaining mature sperm die. In contrast, over two-thirds of males exposed to 36.6 °C are completely sterile. In standard mating trials, earlier exposure to 34.4 °C or 36.6 °C did not affect male courtship behaviour when compared to control males kept at 23 °C. Exposure to high temperatures also did not alter the extent to which males directed courtship toward females of the same species. However, males exposed to 36.6 °C were significantly slower to mate, and had a reduced likelihood of mating, when compared to control males. Overall, exposure to high temperatures did not alter male courtship behaviour, but did lower their likelihood of mating. This suggests that females can distinguish between normal and heat-sterilized males before mating, and that female mate choice may at least partly mitigate the population-level consequences of high-temperature induced male sterility in this species.

Female fruit flies cannot protect stored sperm from high temperature damage.

Recently, it has been demonstrated that heat-induced male sterility is likely to shape population persistence as climate change progresses. However, an under-explored possibility is that females may be able to successfully store and preserve sperm at temperatures that sterilise males, which could ameliorate the impact of male infertility on populations. Here, we test whether females from two fruit fly species can protect stored sperm from a high temperature stress. We find that sperm carried by female Drosophila virilis are almost completely sterilised by high temperatures, whereas sperm carried by female Zaprionus indianus show only slightly reduced fertility. Heat-shocked D. virilis females can recover fertility when allowed to remate, suggesting that the delivered heat-shock is damaging stored sperm and not directly damaging females in this species. The temperatures required to reduce fertility of mated females are substantially lower than the temperatures required to damage mature sperm in males, suggesting that females are worse than males at protecting mature sperm. This suggests that female sperm storage is unlikely to ameliorate the impacts of high temperature fertility losses in males, and instead exacerbates fertility costs of high temperatures, representing an important determinant of population persistence during climate change.

Cognitive remediation for inpatients with psychosis: a systematic review and meta-analysis.

Cognitive difficulties are common in people with psychosis and associated with considerable disability. Cognitive remediation (CR) can reduce the burden of cognitive difficulties and improve functioning. While mental health care has predominantly shifted to the community, people with greater illness severity and complexity, and those with poor response to treatment and concomitant greater cognitive difficulties, continue to receive inpatient care. The aim of this study is to review and evaluate the acceptability and efficacy of CR for inpatients with psychosis. A systematic search was used to identify randomized controlled trials of CR for inpatients with psychosis. Demographic and clinical information was extracted by independent raters together with therapy outcomes. Study quality was assessed using the Cochrane Collaboration Risk of Bias Assessment tool. Standardized mean change for cognitive and functional outcomes was calculated using Hedges's g and used to infer therapy effects with meta-analysis. Twenty studies were identified considering 1509 participants. Results from random-effect models suggested that CR was effective in improving processing speed (g = 0.48), memory (g = 0.48) and working memory (g = 0.56). While there was an indication of improvements in the levels of vocational, social and global functioning, these were less reliable. On average, 7% of participants dropped-out of treatment. Studies methodological quality was moderate. CR is an acceptable intervention for inpatients with psychosis and can lead to significant cognitive improvements. Evidence for improvement in functioning requires more robust and converging evidence. Future research should extend the evaluation of inpatient CR to subsequent post-discharge community functioning and further need for care.

Resistance to natural and synthetic gene drive systems.

Scientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general.

Mate-finding Allee effects can be exacerbated or relieved by sexual cannibalism.

Allee effects occur when individual or population survival decreases due to populations being small or sparse. A key mechanism underlying Allee effects is difficulty in finding mates at low densities. Species may be particularly vulnerable to mate-finding Allee effects if females rely on an abundance of males to reproduce successfully. In sexually cannibalistic species, females may consume males before or after copulation, potentially reducing the supply of males to the point where a mate-finding Allee effect occurs. In this study, we investigate the extent to which sexual cannibalism can modulate mate-finding Allee effects, and the conditions under which sexual cannibalism is likely to be particularly detrimental to population viability. We created an individual-based model that tracked specific females throughout the breeding season and used extinction risk and per capita growth rate to measure the strength of the Allee effects. We varied both founder population size and mate encounter rate independently of each other to expose the mechanism driving the Allee effects. We also analysed how cannibalism-derived female fecundity benefits affected extinction risk. We found that sexual cannibalism could lead to high extinction risk, particularly when cannibalism occurred before copulation, founder population size was small and mate encounter rates were low. However, post-copulatory cannibalism reduced extinction risk, if cannibalism increased female fecundity enough. We found that there were strong threshold effects, in which small changes in encounter rate could strongly alter population extinction risk. We find that sexual cannibalism is likely to negatively impact population survival as population size and mate encounter rate decrease. This may be exacerbated if male quality declines and female hunger increases in declining populations. As many top invertebrate predators, such as spiders and mantises, are sexually cannibalistic, this may have ecosystem-wide impacts. We also suggest that other reproductive behaviours, such as rejecting all but high-quality mates or requiring multiple mates to ensure fertility, are also likely to cause mate-finding Allee effects when habitat quality degrades.

Sexual function and dysfunction among women with anorexia nervosa: A systematic scoping review.

OBJECTIVE: Research suggests that a variety of biological and psychosocial factors are associated with the sexual health of women diagnosed with anorexia nervosa (AN). This systematic scoping review, conducted in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, synthesizes the current literature concerning sexual function and dysfunction in women with AN. METHOD: We searched PubMed, EMBASE, and PsychInfo for literature published until April 2020. All study designs were eligible for inclusion, providing they focused on sexual function and dysfunction in women with AN. Studies that only included outcomes related to gender identity or sexual orientation were excluded. RESULTS: N = 28 studies met criteria for inclusion in the review. All studies were conducted in Western countries and the majority employed either a cohort or cross-sectional design. Although measures of sexual function and dysfunction varied markedly across studies, most studies adopted a biopsychosocial framework. Libido may be linked to body mass index (BMI), while other aspects of sexual functioning and behavior might not be specifically associated with weight status. Limited data are available on evidence-based interventions. DISCUSSION: Sexual dysfunction in women with AN is common. Although some of the variance is explained by low BMI, associated physiological sequelae and other psychosocial factors are also involved. Sexual dysfunction is a relevant clinical problem and clinicians should sensitively incorporate questions related to sexual function into their eating disorder assessments. Future research, using more robust designs and validated outcome measures, is needed to better understand causal pathways between the biological and psychosocial correlates of AN and sexual dysfunction. Identifying predictors of sexual function and dysfunction in more diverse groups of people with AN will support the development of evidence-based therapies.

OBJETIVO: La investigación sugiere que una variedad de factores biológicos y psicosociales están asociados con la salud sexual de las mujeres diagnosticadas con anorexia nervosa (AN). Esta revisión exploratoria sistemática, realizada de acuerdo con las Directrices PRISMA, sintetiza la literatura actual sobre la función y la disfunción sexual en mujeres con AN. MÉTODOS: Se realizaron búsquedas en PubMed, EMBASE y PsychInfo para la literatura publicada hasta abril de 2020. Todos los diseños de estudio fueron elegibles para su inclusión, siempre que se centraran en la función y la disfunción sexual en mujeres con AN. Se excluyeron los estudios que solo incluyeron resultados relacionados con la identidad de género u orientación sexual. RESULTADOS: Un total de N = 28 estudios cumplieron los criterios para su inclusión en la revisión. Todos los estudios se realizaron en países occidentales y la mayoría empleó un diseño de cohorte o transversal. Aunque las medidas de la función y la disfunción sexual variaron notablemente entre los estudios, la mayoría de los estudios adoptaron un marco biopsicosocial. La líbido puede estar relacionada con el IMC, mientras que otros aspectos del funcionamiento y el comportamiento sexual pueden no estar específicamente asociados con el estado de peso corporal. Se dispone de datos limitados sobre intervenciones basadas en evidencia. DISCUSIÓN: La disfunción sexual en mujeres con AN es común y plantea un problema clínico relevante. Aunque parte de la varianza se explica por el bajo IMC y las secuelas fisiológicas asociadas, otros factores psicosociales también están involucrados. Se necesitan investigaciones futuras, que usen diseños más robustos y medidas de resultado validadas, para comprender mejor las vías causales entre los correlatos biológicos y psicosociales de la AN y la disfunción sexual. La identificación de predictores de la función y la disfunción sexual en grupos más diversos de personas con AN apoyará el desarrollo de terapias basadas en la evidencia.

An X-linked meiotic drive allele has strong, recessive fitness costs in female Drosophila pseudoobscura.

Selfish 'meiotic drive' alleles are transmitted to more than 50% of offspring, allowing them to rapidly invade populations even if they reduce the fitness of individuals carrying them. Theory predicts that drivers should either fix or go extinct, yet some drivers defy these predictions by persisting at low, stable frequencies for decades. One possible explanation for this discrepancy is that drivers are especially costly when homozygous, although empirical tests of this idea are rare and equivocal. Here, we measure the fitness of female Drosophila pseudoobscura carrying zero, one or two copies of the X-linked driver sex ratio (SR). SR had strong negative effects on female offspring production and the probability of reproductive failure, and these effects were largely similar across four genetic backgrounds. SR was especially costly when homozygous. We used our fitness measurements to parametrize a population genetic model, and found that the female fitness costs observed here can explain the puzzlingly low allele frequency of SR in nature. We also use the model to show how spatial variation in female mating behaviour, fitness costs of SR and the reduced siring success of SR males can jointly explain the north-south cline in SR frequencies across North America.

Controlling invasive rodents via synthetic gene drive and the role of polyandry.

House mice are a major ecosystem pest, particularly threatening island ecosystems as a non-native invasive species. Rapid advances in synthetic biology offer new avenues to control pest species for biodiversity conservation. Recently, a synthetic sperm-killing gene drive construct called t-Sry has been proposed as a means to eradicate target mouse populations owing to a lack of females. A factor that has received little attention in the discussion surrounding such drive applications is polyandry. Previous research has demonstrated that sperm-killing drivers are extremely damaging to a male's sperm competitive ability. Here, we examine the importance of this effect on the t-Sry system using a theoretical model. We find that polyandry substantially hampers the spread of t-Sry such that release efforts have to be increased three- to sixfold for successful eradication. We discuss the implications of our finding for potential pest control programmes, the risk of drive spread beyond the target population, and the emergence of drive resistance. Our work highlights that a solid understanding of the forces that determine drive dynamics in a natural setting is key for successful drive application, and that exploring the natural diversity of gene drives may inform effective gene drive design.

Eating pathology in midlife women: Similar or different to younger counterparts?

OBJECTIVE: This study examined potential similarities and differences between women with eating disorders (EDs) in midlife and their younger counterparts. METHOD: Seven hundred and three women assessed by a specialist eating disorder service were divided into three groups based on age (18-25, 25-40, and 40+) and compared on a number of clinical and demographic measures. Distribution of ED diagnoses was also examined between groups. RESULTS: Midlife women were less likely to receive a diagnosis of anorexia nervosa and more likely to receive a diagnosis of binge-eating disorder than their younger counterparts. Duration of illness was longer and age of ED onset later in the midlife group but no differences were seen on measures of global ED pathology, psychosocial impairment, or psychological distress. DISCUSSION: This study adds to the developing literature concerning EDs in midlife women, although further work is needed to support the findings presented here and to examine profiles of males presenting to treatment centers.

Causal effects of body mass index on cardiometabolic traits and events: a Mendelian randomization analysis.

Elevated body mass index (BMI) associates with cardiometabolic traits on observational analysis, yet the underlying causal relationships remain unclear. We conducted Mendelian randomization analyses by using a genetic score (GS) comprising 14 BMI-associated SNPs from a recent discovery analysis to investigate the causal role of BMI in cardiometabolic traits and events. We used eight population-based cohorts, including 34,538 European-descent individuals (4,407 type 2 diabetes (T2D), 6,073 coronary heart disease (CHD), and 3,813 stroke cases). A 1 kg/m(2) genetically elevated BMI increased fasting glucose (0.18 mmol/l; 95% confidence interval (CI) = 0.12-0.24), fasting insulin (8.5%; 95% CI = 5.9-11.1), interleukin-6 (7.0%; 95% CI = 4.0-10.1), and systolic blood pressure (0.70 mmHg; 95% CI = 0.24-1.16) and reduced high-density lipoprotein cholesterol (-0.02 mmol/l; 95% CI = -0.03 to -0.01) and low-density lipoprotein cholesterol (LDL-C; -0.04 mmol/l; 95% CI = -0.07 to -0.01). Observational and causal estimates were directionally concordant, except for LDL-C. A 1 kg/m(2) genetically elevated BMI increased the odds of T2D (odds ratio [OR] = 1.27; 95% CI = 1.18-1.36) but did not alter risk of CHD (OR 1.01; 95% CI = 0.94-1.08) or stroke (OR = 1.03; 95% CI = 0.95-1.12). A meta-analysis incorporating published studies reporting 27,465 CHD events in 219,423 individuals yielded a pooled OR of 1.04 (95% CI = 0.97-1.12) per 1 kg/m(2) increase in BMI. In conclusion, we identified causal effects of BMI on several cardiometabolic traits; however, whether BMI causally impacts CHD risk requires further evidence.

Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

Opposite environmental and genetic influences on body size in North American Drosophila pseudoobscura.

BACKGROUND: Populations of a species often differ in key traits. However, it is rarely known whether these differences are associated with genetic variation and evolved differences between populations, or are instead simply a plastic response to environmental differences experienced by the populations. Here we examine the interplay of plasticity and direct genetic control by investigating temperature-size relationships in populations of Drosophila pseudoobscura from North America. We used 27 isolines from three populations and exposed them to four temperature regimes (16°C, 20°C, 23°C, 26°C) to examine environmental, genetic and genotype-by-environment sources of variance in wing size. RESULTS: By far the largest contribution to variation in wing size came from rearing temperature, with the largest flies emerging from the coolest temperatures. However, we also found a genetic signature that was counter to this pattern as flies originating from the northern, cooler population were consistently smaller than conspecifics from more southern, warmer populations when reared under the same laboratory conditions. CONCLUSIONS: We conclude that local selection on body size appears to be acting counter to the environmental effect of temperature. We find no evidence that local adaptation in phenotypic plasticity can explain this result, and suggest indirect selection on traits closely linked with body size, or patterns of chromosome inversion may instead be driving this relationship.

Loci influencing blood pressure identified using a cardiovascular gene-centric array.

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Heritability and genome-wide analyses of problematic peer relationships during childhood and adolescence.

Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4-17 years), and a UK twin sample (TEDS, 4-11 years). Longitudinal twin analysis (TEDS; N ≤ 7,366 twin pairs) showed that peer problems in childhood are heritable (4-11 years, 0.60 < twin-h(2) ≤ 0.71) but genetically heterogeneous from age to age (4-11 years, twin-r(g) = 0.30). GCTA (ALSPAC: N ≤ 5,608, TEDS: N ≤ 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4-12 years, 0.02 < GCTA-h(2)(Meta) ≤ 0.11) though these influences become stronger in adolescence (13-17 years, 0.14 < GCTA-h (2)(ALSPAC) ≤ 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N ≤ 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P ≤ 0.03). Single variant signals (P ≤ 10(-5)) were followed up in TEDS (N ≤ 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N Pedigrees = 793; ACC: N Cases = 1,453/N Controls = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence.

Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.

Does polyandry control population sex ratio via regulation of a selfish gene?

The extent of female multiple mating (polyandry) can strongly impact on the intensity of sexual selection, sexual conflict, and the evolution of cooperation and sociality. More subtly, polyandry may protect populations against intragenomic conflicts that result from the invasion of deleterious selfish genetic elements (SGEs). SGEs commonly impair sperm production, and so are likely to be unsuccessful in sperm competition, potentially reducing their transmission in polyandrous populations. Here, we test this prediction in nature. We demonstrate a heritable latitudinal cline in the degree of polyandry in the fruitfly Drosophila pseudoobscura across the USA, with northern population females remating more frequently in both the field and the laboratory. High remating was associated with low frequency of a sex-ratio-distorting meiotic driver in natural populations. In the laboratory, polyandry directly controls the frequency of the driver by undermining its transmission. Hence we suggest that the cline in polyandry represents an important contributor to the cline in sex ratio in nature. Furthermore, as the meiotic driver causes sex ratio bias, variation in polyandry may ultimately determine population sex ratio across the USA, a dramatic impact of female mating decisions. As SGEs are ubiquitous it is likely that the reduction of intragenomic conflict by polyandry is widespread.

Sex ratio distorting microbes exacerbate arthropod extinction risk in variable environments.

Maternally-inherited sex ratio distorting microbes (SRDMs) are common among arthropod species. Typically, these microbes cause female-biased sex ratios in host broods, either by; killing male offspring, feminising male offspring, or inducing parthenogenesis. As a result, infected populations can experience drastic ecological and evolutionary change. The mechanism by which SRDMs operate is likely to alter their impact on host evolutionary ecology; despite this, the current literature is heavily biased towards a single mechanism of sex ratio distortion, male-killing. Furthermore, amidst the growing concerns surrounding the loss of arthropod diversity, research into the impact of SRDMs on the viability of arthropod populations is generally lacking. In this study, using a theoretical approach, we model the epidemiology of an understudied mechanism of microbially-induced sex ratio distortion-feminisation-to ask an understudied question-how do SRDMs impact extinction risk in a changing environment? We constructed an individual-based model and measured host population extinction risk under various environmental and epidemiological scenarios. We also used our model to identify the precise mechanism modulating extinction. We find that the presence of feminisers increases host population extinction risk, an effect that is exacerbated in highly variable environments. We also identified transmission rate as the dominant epidemiological trait responsible for driving extinction. Finally, our model shows that sex ratio skew is the mechanism driving extinction. We highlight feminisers and, more broadly, SRDMs as important determinants of the resilience of arthropod populations to environmental change.