This study investigated genetic correlations of longissimus muscle fatty acid composition with 32 traits related to growth, carcass, fat deposition and meat quality in 2448 pigs from six populations ...using genome wide SNP data. Most of significant loci for saturated (C14:0, C16:0 and C18:0) and mono-saturated fatty acids (C18:1n9 and C16:1n7) identified in GWAS, including those near ELOVL6, SCD and FASN genes, displayed negligible or weak effects on all the 32 traits. Fat deposition traits were the most relevant traits for fatty acid composition in genetic correlations. Backfat thickness and intramuscular fat content consistently showed strong negative genetic correlations with C18:2n6, and positive genetic correlations with C18:1n9 at least five populations. Intramuscular fat content consistently has positive correlations with saturated fatty acids (SFA) in six populations. This study provided insights into shared genetic control of fatty acid composition and the other economic traits, which is helpful in design of breeding strategies to genetically improve fatty acid composition in pork.
Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial ...genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.
We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.
Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.
Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Genetic correlations between the sexes can constrain the evolution of sexual dimorphism and be difficult to alter, because traits common to both sexes share the same genetic underpinnings. We tested ...whether artificial correlational selection favoring specific combinations of male and female traits within families could change the strength of a very high between-sex genetic correlation for flower size in the dioecious plant Silene latifolia. This novel selection dramatically reduced the correlation in two of three selection lines in fewer than five generations. Subsequent selection only on females in a line characterized by a lower between-sex genetic correlation led to a significantly lower correlated response in males, confirming the potential evolutionary impact of the reduced correlation. Although between-sex genetic correlations can potentially constrain the evolution of sexual dimorphism, our findings reveal that these constraints come not from a simple conflict between an inflexible genetic architecture and a pattern of selection working in opposition to it, but rather a complex relationship between a changeable correlation and a form of selection that promotes it. In other words, the form of selection on males and females that leads to sexual dimorphism may also promote the genetic phenomenon that limits sexual dimorphism.
In most animals, body mass varies with ecological conditions and is expected to reflect how much energy can be allocated to reproduction and survival. Because the sexes often differ in their resource ...acquisition and allocation strategies, variations in adult body mass and their consequences on fitness can differ between the sexes.
Assessing the relative contributions of environmental and genetic effects (i.e. heritability)—and whether these effects and their fitness consequences are sex‐specific—is essential to gain insights into the evolution of sexual dimorphism and sexual conflicts.
We used 20+ years of data to study the sources of variation in adult body mass and associated fitness consequences in a bird with biparental care, the Alpine swift (Tachymarptis melba). Swifts appear monomorphic to human observers, though subtle dimorphisms are present.
We first investigated the effects of weather conditions on adult body mass using a sliding window analysis approach. We report a positive effect of temperature and a negative effect of rainfall on adult body mass, as expected for an aerial insectivorous bird. We then quantified the additive genetic variance and heritability of body mass in both sexes and assessed the importance of genetic constraints on mass evolution by estimating the cross‐sex genetic correlation. Heritability was different from zero in both sexes at ~0.30. The positive cross‐sex genetic correlation and comparable additive genetic variance between the sexes suggest the possibility for evolutionary constraints when it comes to body mass. Finally, we assessed the sex‐specific selection on adjusted body mass using multiple fitness components. We report directional positive and negative selection trending towards stabilizing and diversifying selection on females and males respectively in relation to the weighted proportion of surviving fledglings.
Overall, these results suggest that while body mass may be able to respond to environmental conditions and evolve, genetic constraints would result in similar changes in both sexes or an overall absence of response to selection. It remains unclear whether the weak (1%) dimorphism in Alpine swift body mass we report is simply a result of the similar fitness peaks between the sexes or of genetic constraints.
Using 20+ years of data, we investigated the sex‐specific genetic architecture and selection on body mass in a weakly dimorphic wild bird, the Alpine swift. Our results provide insights as to the evolution of sexual size dimorphism and sexual conflicts in nature, which remain major unresolved questions in evolutionary biology.
We aimed to increase our understanding of the genetic determinants of vitamin D levels by undertaking a large-scale genome-wide association study (GWAS) of serum 25 hydroxyvitamin D (25OHD). To do ...so, we used imputed genotypes from 401,460 white British UK Biobank participants with available 25OHD levels, retaining single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) > 0.1% and imputation quality score > 0.3. We performed a linear mixed model GWAS on standardized log-transformed 25OHD, adjusting for age, sex, season of measurement, and vitamin D supplementation. These results were combined with those from a previous GWAS including 42,274 Europeans. In silico functional follow-up of the GWAS results was undertaken to identify enrichment in gene sets, pathways, and expression in tissues, and to investigate the partitioned heritability of 25OHD and its shared heritability with other traits. Using this approach, the SNP heritability of 25OHD was estimated to 16.1%. 138 conditionally independent SNPs were detected (p value < 6.6 × 10−9) among which 53 had MAF < 5%. Single variant association signals mapped to 69 distinct loci, among which 63 were previously unreported. We identified enrichment in hepatic and lipid metabolism gene pathways and enriched expression of the 25OHD genes in liver, skin, and gastrointestinal tissues. We observed partially shared heritability between 25OHD and socio-economic traits, a feature which may be mediated through time spent outdoors. Therefore, through a large 25OHD GWAS, we identified 63 loci that underline the contribution of genes outside the vitamin D canonical metabolic pathway to the genetic architecture of 25OHD.
Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly ...impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction.
To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424).
Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment—the relationship is positive in bipolar disorder but negative in major depressive disorder.
The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.
Genome-wide analyses of common and rare genetic variations have documented the heritability of major psychiatric disorders, established their highly polygenic genetic architecture, and identified ...hundreds of contributing variants. In recent years, these studies have illuminated another key feature of the genetic basis of psychiatric disorders: the important role and pervasive nature of pleiotropy. It is now clear that a substantial fraction of genetic influences on psychopathology transcend clinical diagnostic boundaries. In this review, we summarize evidence in psychiatry for pleiotropy at multiple levels of analysis: from overall genome-wide correlation to biological pathways and down to the level of individual loci. We examine underlying mechanisms of observed pleiotropy, including genetic effects on neurodevelopment, diverse actions of regulatory elements, mediated effects, and spurious associations of genomic variation with multiple phenotypes. We conclude with an exploration of the implications of pleiotropy for understanding the genetic basis of psychiatric disorders, informing nosology, and advancing the aims of precision psychiatry and genomic medicine.
Genetically correlated traits do not evolve independently, and the covariances between traits affect the rate at which a population adapts to a specified selection regime. To measure the impact of ...genetic covariances on the rate of adaptation, we compare the rate fitness increases given the observed G matrix to the expected rate if all the covariances in the G matrix are set to zero. Using data from the literature, we estimate the effect of genetic covariances in real populations. We find no net tendency for covariances to constrain the rate of adaptation, though the quality and heterogeneity of the data limit the certainty of this result. There are some examples in which covariances strongly constrain the rate of adaptation but these are balanced by counter examples in which covariances facilitate the rate of adaptation; in many cases, covariances have little or no effect. We also discuss how our metric can be used to identify traits or suites of traits whose genetic covariances to other traits have a particularly large impact on the rate of adaptation.
Intelligence is highly heritable
and a major determinant of human health and well-being
. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence
, but ...much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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