Expressive

rs12369179 - ZCCHC8

Magnitude 2.2 · 8 studies on file

Reported associations

  • Genetic architecture reconciles linkage and association studies of complex traits. - Nature genetics (2024) · Sidorenko J, Couvy-Duchesne B, Kemper KE, Moen GH, Bhatta L, Åsvold BO, Mägi R, Ani A, Wang R, Nolte IM, Gordon S, Hayward C, Campbell A, Benjamin DJ, Cesarini D, Evans DM, Goddard ME, Haley CS, Porteous D, Medland SE, Martin NG, Snieder H, Metspalu A, Hveem K, Brumpton B, Visscher PM, Yengo L · PubMed 39375568

    Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratif

  • Genetic Evidence for Different Adiposity Phenotypes and Their Opposing Influences on Ectopic Fat and Risk of Cardiometabolic Disease. - Diabetes (2021) · Martin S, Cule M, Basty N, Tyrrell J, Beaumont RN, Wood AR, Frayling TM, Sorokin E, Whitcher B, Liu Y, Bell JD, Thomas EL, Yaghootkar H · PubMed 33980691

    To understand the causal role of adiposity and ectopic fat in type 2 diabetes and cardiometabolic diseases, we aimed to identify two clusters of adiposity genetic variants: one with "adverse" metabolic effects (UFA) and the other with, paradoxically, "favorable" metabolic effects (FA). We performed a multivariate genome-wide association study using body fat percentage and metabolic biomarkers from UK Biobank and identified 38 UFA and 36 FA variants. Adiposity-increasing alleles were associated with an adverse metabolic profile, higher risk of disease, higher CRP, and higher fat in subcutaneous and visceral adipose tissue, liver, and pancreas for UFA and a favorable metabolic profile, lower risk of disease, higher CRP and higher subcutaneous adipose tissue but lower liver fat for FA. We det

  • A scalable variational inference approach for increased mixed-model association power - Unknown journal (n.d.) · Unknown authors · PubMed 39789286

    ABSTRACT: The rapid growth of modern biobanks is creating new opportunities for large-scale genome-wide association studies (GWASs) and the analysis of complex traits. However, performing GWASs on millions of samples often leads to trade-offs between computational efficiency and statistical power, reducing the benefits of large-scale data collection efforts. We developed Quickdraws, a method that increases association power in quantitative and binary traits without sacrificing computational efficiency, leveraging a spike-and-slab prior on variant effects, stochastic variational inference and graphics processing unit acceleration. We applied Quickdraws to 79 quantitative and 50 binary traits in 405,088 UK Biobank samples, identifying 4.97% and 3.25% more associations than REGENIE and 22.71%

  • Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases - Unknown journal (n.d.) · Unknown authors · PubMed 27790247

    ABSTRACT: Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood gl

  • Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry - Unknown journal (n.d.) · Unknown authors · PubMed 30239722

    ABSTRACT: Abstract More than one in three adults worldwide is either overweight or obese. Epidemiological studies indicate that the location and distribution of excess fat, rather than general adiposity, are more informative for predicting risk of obesity sequelae, including cardiometabolic disease and cancer. We performed a genome-wide association study meta-analysis of body fat distribution, measured by waist-to-hip ratio (WHR) adjusted for body mass index (WHRadjBMI), and identified 463 signals in 346 loci. Heritability and variant effects were generally stronger in women than men, and we found approximately one-third of all signals to be sexually dimorphic. The 5% of individuals carrying the most WHRadjBMI-increasing alleles were 1.62 times more likely than the bottom 5% to have a WHR

  • Shared Genetic and Experimental Links between Obesity-Related Traits and Asthma Subtypes in UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 31669095

    ABSTRACT: Background: Clinical and epidemiological studies have shown that obesity is associated with asthma and that these associations differ by asthma subtypes. Little is known about the shared genetic components between obesity and asthma. Objective: To identify shared genetic associations between obesity-related traits and asthma subtypes in adults. Methods: A cross-trait genome-wide association study (GWAS) was performed using 457,822 individuals of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma via GWAS was sought using results from obese vs. lean mouse RNA-seq and RT-PCR experiments. Results: We found a substantial positive genetic correlation between BMI and later-onset

  • Beyond apples and pears: sex-specific genetics of body fat percentage - Unknown journal (n.d.) · Unknown authors · PubMed 37867527

    ABSTRACT: Introduction Biological sex influences both overall adiposity and fat distribution. Further, testosterone and sex hormone binding globulin (SHBG) influence adiposity and metabolic function, with differential effects of testosterone in men and women. Here, we aimed to perform sex-stratified genome-wide association studies (GWAS) of body fat percentage (BFPAdj) (adjusting for testosterone and sex hormone binding globulin (SHBG)) to increase statistical power. Methods GWAS were performed in white British individuals from the UK Biobank (157,937 males and 154,337 females). To avoid collider bias, loci associated with SHBG or testosterone were excluded. We investigated association of BFPAdj loci with high density cholesterol (HDL), triglyceride (TG), type 2 diabetes (T2D), coronary ar

  • GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer - Unknown journal (n.d.) · Unknown authors · PubMed 34021172

    ABSTRACT: Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to can

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