Genetic correlations between males and females are often thought to constrain the evolution of sexual dimorphism. However, sexually dimorphic traits and the underlying sexually dimorphic gene ...expression patterns are often rapidly evolving. We explore this apparent paradox by measuring the genetic correlation in gene expression between males and females (C
mf) across broad evolutionary timescales, using two RNA-sequencing data sets spanning multiple populations and multiple species. We find that unbiased genes have higher C
mf than sex-biased genes, consistent with intersexual genetic correlations constraining the evolution of sexual dimorphism. However, we found that highly sex-biased genes (both male and female biased) also had higher tissue specificity, and unbiased genes had greater expression breadth, suggesting that pleiotropy may constrain the breakdown of intersexual genetic correlations. Finally, we show that genes with high C
mf showed some degree of sex-specific changes in gene expression in males and females. Together, our results suggest that genetic correlations between males and females may be less important in constraining the evolution of sex-biased gene expression than pleiotropy. Sex-specific regulatory variation and tissue specificity may resolve the paradox of widespread sex bias within a largely shared genome.
Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain ...unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders—peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10−5) bivariate local genetic correlations between cognitive traits, AD, and GIT disorders (including IBD). Mendelian randomisation analysis suggests a risk-decreasing causality of educational attainment, intelligence, and other cognitive traits on PUD and GERD, but not IBD, and a putative association of GERD with cognitive function decline. Gene-based analysis reveals a significant gene-level genetic overlap of cognitive traits with AD and GIT disorders (IBD inclusive, pbinomial-test = 1.18 × 10−3−2.20 × 10−16). Our study supports the protective roles of genetically-influenced educational attainments and other cognitive traits on the risk of GIT disorders and highlights a putative association of GERD with cognitive function decline. Findings from local genetic correlation analysis provide novel insights, indicating that the relationship of IBD with cognitive traits (and AD) will depend largely on their local effects across the genome.
Trade-offs and constraints are inherent to life, and studies of these phenomena play a central role in both organismal and evolutionary biology. Trade-offs can be defined, categorized, and studied in ...at least six, not mutually exclusive, ways. (1) Allocation constraints are caused by a limited resource (e.g., energy, time, space, essential nutrients), such that increasing allocation to one component necessarily requires a decrease in another (if only two components are involved, this is referred to as the Y-model, e.g., energy devoted to size versus number of offspring). (2) Functional conflicts occur when features that enhance performance of one task decrease performance of another (e.g., relative lengths of in-levers and out-levers, force-velocity trade-offs related to muscle fiber type composition). (3) Shared biochemical pathways, often involving integrator molecules (e.g., hormones, neurotransmitters, transcription factors), can simultaneously affect multiple traits, with some effects being beneficial for one or more components of Darwinian fitness (e.g., survival, age at first reproduction, fecundity) and others detrimental. (4) Antagonistic pleiotropy describes genetic variants that increase one component of fitness (or a lower-level trait) while simultaneously decreasing another. (5) Ecological circumstances (or selective regime) may impose trade-offs, such as when foraging behavior increases energy availability yet also decreases survival. (6) Sexual selection may lead to the elaboration of (usually male) secondary sexual characters that improve mating success but handicap survival and/or impose energetic costs that reduce other fitness components. Empirical studies of trade-offs often search for negative correlations between two traits that are the expected outcomes of the trade-offs, but this will generally be inadequate if more than two traits are involved and especially for complex physiological networks of interacting traits. Moreover, trade-offs often occur only in populations that are experiencing harsh environmental conditions or energetic challenges at the extremes of phenotypic distributions, such as among individuals or species that have exceptional athletic abilities. Trade-offs may be (partially) circumvented through various compensatory mechanisms, depending on the timescale involved, ranging from acute to evolutionary. Going forward, a pluralistic view of trade-offs and constraints, combined with integrative analyses that cross levels of biological organization and traditional boundaries among disciplines, will enhance the study of evolutionary organismal biology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral ...neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.
Abstract Nicotine dependence is highly comorbid with schizophrenia, and the etiology of the comorbidity is unknown. To determine whether there is a genetic correlation of smoking behavior with ...schizophrenia, genome-wide association study (GWAS) meta-analysis results from five smoking phenotypes (ever/never smoker (N = 74,035), age of onset of smoking (N = 28,647), cigarettes smoked per day (CPD, N = 38,860), nicotine dependence (N = 10,666), and current/former smoker (N = 40,562)) were compared to GWAS meta-analysis results from schizophrenia (N = 79,845) using linkage disequilibrium (LD) score regression. First, the SNP heritability ( h2 g ) of each of the smoking phenotypes was computed using LD score regression (ever/never smoker h2 g = 0.08, age of onset of smoking h2 g = 0.06, CPD h2 g = 0.06, nicotine dependence h2 g = 0.15, current/former smoker h2 g = 0.07, p < 0.001 for all phenotypes). The SNP heritability for nicotine dependence was statistically higher than the SNP heritability for the other smoking phenotypes (p < 0.0005 for all two-way comparisons). Next, a statistically significant (p < 0.05) genetic correlation was observed between schizophrenia and three of the five smoking phenotypes (nicotine dependence r g = 0.14, CPD r g = 0.12, and ever/never smoking r g = 0.10). These results suggest that there is a component of common genetic variation that is shared between smoking behaviors and schizophrenia.
Abstract
Using a cloned Eucalyptus urophylla × E. tereticornis family, the present study estimated clonal mean repeatability, inter-trait correlation, and clone-by-site interactions for height (H) ...and diameter at breast height (D) across 0.5–8 years of age as well as 8-year-old wood basic density (BD8), cellulose content (CC8), hemi-cellulose content (HC8), Klason lignin content (LC8), and lignin syringyl-to-guaiacyl ratio (S/G8). Clonal mean repeatability estimates were 0.40–0.91 for growth traits H and D over 0.5–8 years and 0.50–0.87 for wood properties at age 8 for three separate sites (except that of 0.01 for HC8 at Yanxi) and across sites, indicating moderate to high levels of genetic control of the traits investigated. H had high positive genetic correlation with D. Growth traits (H and/or D) showed generally positive genetic correlation with BD8 and CC8 while negative with HC8 and LC8. Significant genotype-by-environment (clone-by-site) interactions were observed for most traits, suggesting that clones should be matched to sites to increase genetic gain. Our results suggest that there is potential to use E. urophylla × E. tereticornis clones to increase yield with desirable wood properties in Southern China.
Landscape genetics seeks to determine the effect of landscape features on gene flow and genetic structure. Often, such analyses are intended to inform conservation and management. However, depending ...on the many factors that influence the time to reach equilibrium, genetic structure may more strongly represent past rather than contemporary landscapes. This well‐known lag between current demographic processes and population genetic structure often makes it challenging to interpret how contemporary landscapes and anthropogenic activity shape gene flow. Here, we review the theoretical framework for factors that influence time lags, summarize approaches to address this temporal disconnect in landscape genetic studies, and evaluate ways to make inferences about landscape change and its effects on species using genetic data alone or in combination with other data. Those approaches include comparing correlation of genetic structure with historical versus contemporary landscapes, using molecular markers with different rates of evolution, contrasting metrics of genetic structure and gene flow that reflect population genetic processes operating at different temporal scales, comparing historical and contemporary samples, combining genetic data with contemporary estimates of species distribution or movement, and controlling for phylogeographic history. We recommend using simulated data sets to explore time lags in genetic structure, and argue that time lags should be explicitly considered both when designing and interpreting landscape genetic studies. We conclude that the time lag problem can be exploited to strengthen inferences about recent landscape changes and to establish conservation baselines, particularly when genetic data are combined with other data.
Inbreeding can cause an important bias in the estimates of quantitative genetic parameters, which in turn can affect the estimated potential for a selection response in species that are simultaneous ...hermaphrodite with partial self-fertilization. In the present study, the biases caused by self-fertilization on heritability (h2) estimates for productive traits were assessed at different ages in the tropical hermaphrodite pectinid Argopecten nucleus. Self-fertilization rates were estimated in both oocytes and adults, as the percentage of zygotes formed from unfertilized oocytes and by paternity analysis using microsatellite genetic markers, respectively. Fifty sexually mature individuals were individually spawned and genotyped using microsatellite markers. The sperm of one individual used as a male was used to fertilize the oocytes of 4 other individuals, generating 10 half-sibling families (HS) and 40 full-siblings families (FS). At the age of 3.5 months, the total weight, and the length, height, and width of the shell of 60 animals per FS family were individually measured. At the age of 9 months, the same measurements were repeated in the same individuals, which were then euthanized to weigh the soft tissues. In addition, the fecundity was estimated in each individual (number of oocytes produced), and a paternity analysis was performed. No significant differences were found in the average inbreeding rates estimated in oocytes and adults. However, no significant correlation was observed in the estimates of family self-fertilization rates when using both methods. The individuals derived from crossbreeding showed higher average values for productive traits than those produced by selfing, although interactions between the genotype and the depth of culture were observed in both groups. The h2 estimates using statistical models that consider self-fertilization in adults (models II and III) were lower than those observed when self-fertilization rates were estimated in oocytes, or not included in the model. However, the genetic correlations between the traits were similar using both methods for estimating self-fertilization rates. The present results suggest that self-fertilization results in inbreeding depression and induces an overestimation of the h2 for productive traits, but it does not affect estimates of genetic correlations or genotype by environment interactions.
•First report of inbreeding depression in A. nucleus.•Spontaneous development of unfertilized oocytes does not predict inbreeding in adults.•Selfing affects h2 estimations but not the GEI or genetic correlations among traits.•The accuracy of h2 estimations can be improved by inclusion of individual inbreeding.
Growth is one of the most important traits of commercial fishes. Bighead carp are intensively cultured in China and some Asian countries; however, the genetic basis of growth is less understood. In ...this study, we calculated the heritability of growth-related traits in a mixed population of 840 bighead carp and estimated growth-related QTL in a family of bighead carp using bulked segregation analysis of resequencing data. High phenotypic (0.70–0.95) and genetic (0.77–0.97) correlations were found between all growth-related traits. Estimated heritability of 0.20 ± 0.11, 0.28 ± 0.14, 0.32 ± 0.16, 0.14 ± 0.11 and 0.12 ± 0.09 were obtained for body weight, body height, head length, total length, and body length in bighead carp with seven month old. In the BSA analysis for progeny with extreme segregated body weight of a single family, three regions located in LG01, LG11 and LG22, respectively with a total length of 17.84 Mb which were obtained according to correlation thresholds. Annotation of genes within this region yielded 120 and 61 nonsynonymous and code-shifting mutations, respectively, by comparing SNPs and InDel between the two growth difference groups. Finally, 14 candidate genes, including T-box transcription factor 3, transcription factor E2F2, paired box gene 9, and fibroblast growth factor 6b were identified. Association analysis and mRNA levels revealed that paired box gene 9 and fibroblast growth factor 6b were significantly associated with growth-related traits in extreme growth samples. These results provide insights into the genetic mechanisms underlying the regulation of growth and development in the bighead carp.
•Calculated the heritability of growth traits in a mixed population of 840 bighead carp.•A region of 17.84 MB was located by BSA analysis between groups of weight extremes.•181 genes with genotypic differences were annotated and 14 candidate genes were identified.•Pax9 and lrp6 were significantly associated with growth by mRNA expression and SNP association analysis.
Background Previous studies reported that endometriosis may have a higher risk of arthritis. However, it remains unclear whether the association between endometriosis and arthritis has genetic ...correlations, or the relationship is causal. Linkage Disequilibrium Score (LDSC) and Mendelian Randomization (MR) analyses use genetic variation as a natural experiment to explore genetic correlations and causal inferences from observational data, reducing unmeasured confounding factors. Method Participants (aged 20-54 years, n = 2,915) for the cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES). Endometriosis and arthritis were diagnosed based on self-reported by reproductive health and medical condition questionnaire. Weighted multivariable logistic regression was used to explore the relationship between endometriosis and arthritis. LDSC and MR analysis were performed using the genome-wide association study (GWAS) summary statistics to identify the causal association. Result A significant positive association between endometriosis and arthritis was found after multivariable adjustment (OR = 1.89; 95% CI: 1.33, 2.67). When exploring different types of arthritis, a positive association was revealed with rheumatoid arthritis (RA), other types of arthritis, and cases that the arthritis type were unknown, with an OR of 2.07 (95% CI: 1.03, 4.17), 2.78 (95% CI: 1.30, 5.95), and 2.06 (95% CI: 1.36, 3.11), respectively. However, genetic correlation analysis between endometriosis and RA did not reveal any significant findings (all P values > 0.05). Moreover, MR analysis also failed to identify a causal relationship between endometriosis and RA (all P values > 0.05). Conclusion Cross-sectional study identified a significant positive association between endometriosis and arthritis among US women, especially among RA, while findings based on LDSC and MR analysis did not support a genetic correlation or causal role. These findings suggest that clinicians should pay more attention to the coexistence of RA in endometriosis patients and explore the shared pathophysiological mechanisms of these two disorders, with a particular focus on extrinsic factors rather than intrinsic genetic inheritance.
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