Expressive

rs10498767 - RCAN2

Magnitude 2.2 · 5 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

  • Leveraging Polygenic Functional Enrichment to Improve GWAS Power. - American journal of human genetics (2019) · Kichaev G, Bhatia G, Loh PR, Gazal S, Burch K, Freund MK, Schoech A, Pasaniuc B, Price AL · PubMed 30595370

    Functional genomics data has the potential to increase GWAS power by identifying SNPs that have a higher prior probability of association. Here, we introduce a method that leverages polygenic functional enrichment to incorporate coding, conserved, regulatory, and LD-related genomic annotations into association analyses. We show via simulations with real genotypes that the method, functionally informed novel discovery of risk loci (FINDOR), correctly controls the false-positive rate at null loci and attains a 9%-38% increase in the number of independent associations detected at causal loci, depending on trait polygenicity and sample size. We applied FINDOR to 27 independent complex traits and diseases from the interim UK Biobank release (average N = 130K). Averaged across traits, we attaine

  • Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood - Unknown journal (n.d.) · Unknown authors · PubMed 37280435

    ABSTRACT: Aims/hypothesis Determining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical. Methods By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity. Results We found tha

  • 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

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