Transitions in sex determination mechanisms through parental and sexual antagonism
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Pelvic physical therapy for male sexual disorders: a narrative review
Pelvic physical therapy is an evidence-based, first-line treatment for many pelvic floor disorders and sexual dysfunction. Studies have shown that pelvic physical therapy programs can both improve pelvic floor dysfunctions and sexual function. This article aims to provide an overview of the current state of the art regarding pelvic physical therapy for male sexual dysfunction to inform healthcare providers who treat men with sexual dysfunction better. A literature review was performed in Google Scholar, PubMed, and Science Direct to find review articles, research articles, and case studies about the effect of pelvic physical therapy treatments for male sexual dysfunction. Twenty-six articles were found about various pelvic physical therapy interventions. Besides this overview of the literature, an overview of interventions used in clinical practice is also provided. This narrative review supports the potential efficacy of pelvic physical therapy in addressing male sexual dysfunction. Pelvic physical therapy approaches that comprise exercise modalities, electrotherapy approaches, manipulative techniques, lifestyle changes, behavioral suggestions, and pain management strategies, should be suggested for potential benefits in improving erectile function, premature ejaculation, and sexual dysfunction-associated chronic pelvic pain. More research is needed to examine the effect of pelvic physical therapy on hypoactive sexual desire and delayed ejaculation.
Atlas of imprinted and allele-specific DNA methylation in the human body
Allele-specific DNA methylation reflects genetic variation and parentally-inherited changes, and is involved in gene regulation and pathologies. Yet, our knowledge of this phenomenon is largely limited to blood. Here we present a comprehensive atlas of allele-specific DNA methylation using deep whole-genome sequencing across 39 normal human cell types. We identified 325k regions, covering 6% of the genome and 11% of CpGs, that show a bimodal distribution of methylated and unmethylated molecules. In 34k of these regions, genetic variations at individual alleles segregate with methylation patterns, validating allele-specific methylation. We also identified 460 regions showing parental allele-specific methylation, the majority of which are novel, as well as 78 regions associated with known imprinted genes. Surprisingly, sequence-dependent and parental allele-dependent methylation is often restricted to specific cell types, revealing unappreciated variation of allele-specific methylation across the human body. Finally, we validate tissue-specific, maternal allele-specific methylation of CHD7, offering a potential mechanism for the paternal bias in the inheritance mode of CHARGE syndrome associated with this gene. The atlas provides a resource for studying allele-specific methylation and regulatory mechanisms underlying imprinted expression in specific human cell types.
Family-based genome-wide association study designs for increased power and robustness
Family-based genome-wide association studies (FGWASs) use random, within-family genetic variation to remove confounding from estimates of direct genetic effects (DGEs). Here we introduce a ‘unified estimator’ that includes individuals without genotyped relatives, unifying standard and FGWAS while increasing power for DGE estimation. We also introduce a ‘robust estimator’ that is not biased in structured and/or admixed populations. In an analysis of 19 phenotypes in the UK Biobank, the unified estimator in the White British subsample and the robust estimator (applied without ancestry restrictions) increased the effective sample size for DGEs by 46.9% to 106.5% and 10.3% to 21.0%, respectively, compared to using genetic differences between siblings. Polygenic predictors derived from the unified estimator demonstrated superior out-of-sample prediction ability compared to other family-based methods. We implemented the methods in the software package snipar in an efficient linear mixed model that accounts for sample relatedness and sibling shared environment.
Genetic architectures of childhood maltreatment and causal influence of childhood maltreatment on health outcomes in adulthood
Childhood maltreatment is increasingly recognized as a pivotal risk factor for adverse health outcomes. However, comprehensive analyses of its long-term impact are scarce. This study aims to fill this gap by examining the genetic architectures of childhood maltreatment and its influence on adult health and socioeconomic outcomes. Utilizing data from the UK Biobank (N = 129,017), we conducted sex-combined and sex-stratified genome-wide association studies to identify genomic loci associated with five childhood maltreatment subtypes. We then performed genetic correlation and Mendelian randomization (MR) analyses to assess the effects of childhood maltreatment on high-burden diseases, healthcare costs, lifespan, and educational attainment. We identified several novel loci for childhood maltreatment, including one locus for sexual abuse in sex-combined analysis, one novel locus for sexual abuse in males, one locus for emotional neglect in females, and one locus for sexual abuse in females. The pairwise genetic correlations between subtypes of childhood maltreatment were moderate to high, and similar patterns of genetic correlations between childhood maltreatment subtypes were observed in males and females. Childhood maltreatment was genetically correlated with ten out of 16 high-burden diseases significantly after multiple testing correction. Moreover, MR analyses suggest childhood maltreatment may increase the risk of age-related and other hearing loss, low back pain, major depressive disorder, and migraine in adulthood, and reduce the lifespan. Our study elucidates the genetic architecture of specific childhood maltreatment subtypes and the influence of childhood maltreatment on health outcomes in adulthood, highlighting the enduring influence of childhood maltreatment on lifelong health consequences. It is important to develop prevention strategies to lower the incidence of childhood maltreatment and provide support and care for victims of childhood maltreatment for better long-term health outcomes in the population.
No evidence of positive causal effects of maternal and paternal age at first birth on children’s test scores at age 10 years
Research has shown that higher maternal and paternal age is positively associated with children’s education. Debate continues as to whether these relationships are causal. This is of great interest given the postponement of first births in almost all developed countries during the twentieth century. Here we use an instrumental variable approach (Mendelian randomization) using maternal and paternal polygenic indices (PGIs) for age at first birth—while conditioning on the child’s PGI for age at first birth—to identify the causal effects of maternal and paternal age at first birth on children’s test scores based on data from the Norwegian Mother, Father and Child Cohort study. We do not find evidence of positive causal effects of both maternal and paternal age at first birth on children’s test scores at age 10 years once the children’s PGI and correlations among different PGIs are controlled for. We therefore conclude that our results do not provide evidence in favour of sociological theories that predict positive causal effects of parental age on children’s educational attainment.
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