Expressive

rs10995311 - ADO

Magnitude 2.2 · 8 studies on file

Reported associations

  • A cross-population atlas of genetic associations for 220 human phenotypes. - Nature genetics (2021) · Sakaue S, Kanai M, Tanigawa Y, Karjalainen J, Kurki M, Koshiba S, Narita A, Konuma T, Yamamoto K, Akiyama M, Ishigaki K, Suzuki A, Suzuki K, Obara W, Yamaji K, Takahashi K, Asai S, Takahashi Y, Suzuki T, Shinozaki N, Yamaguchi H, Minami S, Murayama S, Yoshimori K, Nagayama S, Obata D, Higashiyama M, Masumoto A, Koretsune Y, Ito K, Terao C, Yamauchi T, Komuro I, Kadowaki T, Tamiya G, Yamamoto M, Nakamura Y, Kubo M, Murakami Y, Yamamoto K, Kamatani Y, Palotie A, Rivas MA, Daly MJ, Matsuda K, Okada Y · PubMed 34594039

    Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (n = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wid

  • 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 Association of Albuminuria with Cardiometabolic Disease and Blood Pressure. - American journal of human genetics (2019) · Haas ME, Aragam KG, Emdin CA, Bick AG, Hemani G, Davey Smith G, Kathiresan S · PubMed 30220432

    Excretion of albumin in urine, or albuminuria, is associated with the development of multiple cardiovascular and metabolic diseases. However, whether pathways leading to albuminuria are causal for cardiometabolic diseases is unclear. We addressed this question using a Mendelian randomization framework in the UK Biobank, a large population-based cohort. We first performed a genome-wide association study for albuminuria in 382,500 individuals and identified 32 new albuminuria loci. We constructed albuminuria genetic risk scores and tested for association with cardiometabolic diseases. Genetically elevated albuminuria was strongly associated with increased risk of hypertension (1.38 OR; 95% CI, 1.27-1.50 per 1 SD predicted increase in albuminuria, p = 7.01 × 10 ). We then examined bidire

  • Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci - Unknown journal (n.d.) · Unknown authors · PubMed 27618448

    ABSTRACT: Meta-analyses of association results for blood pressure using exome-centric single-variants and gene-based tests identified 31 novel loci in discovery among 146,562 individuals with follow-up and meta-analysis in 180,726 additional individuals (Ntotal=327,288). These blood pressure loci are enriched for known cardiometabolic trait variants. Associations were also observed for the aggregation of rare/low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interact

  • 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%

  • Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum - Unknown journal (n.d.) · Unknown authors · PubMed 40229599

    ABSTRACT: Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095-246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary

  • A Genomics England haplotype reference panel and imputation of UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 39134668

    ABSTRACT: We built a reference panel with 342 million autosomal variants using 78,195 individuals from the Genomics England (GEL) dataset, achieving a phasing switch error rate of 0.18% for European samples and imputation quality of r2 = 0.75 for variants with minor allele frequencies as low as 2 × 10−4 in white British samples. The GEL-imputed UK Biobank genome-wide association analysis identified 70% of associations found by direct exome sequencing (P < 2.18 × 10−11), while extending testing of rare variants to the entire genome. Coding variants dominated the rare-variant genome-wide association results, implying less disruptive effects of rare non-coding variants. A Genomics England haplotype reference panel constructed using sequence data from 78,195 individuals

  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension - Unknown journal (n.d.) · Unknown authors · PubMed 27618447

    ABSTRACT: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic va

Auto-generated from study metadata. AI-synthesised commentary is added when this entry is regenerated through content-service's LLM mode.