Expressive

rs12206717 - TULP4

Magnitude 2.0 · 5 studies on file

Reported associations

  • 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

  • Combining cross-sectional and longitudinal genomic approaches to identify determinants of cognitive and physical decline - Unknown journal (n.d.) · Unknown authors · PubMed 40374629

    ABSTRACT: Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up with LD-score regression and Mendelian Randomization (MR) analyses. Focusing on global cognitive and physical function, we observed marked differences between baseline function (θ) and accelerated decline (Δ). Both outcomes showed distinct heritability levels (e.g., 31.38% versus 3.15%

  • A genome-wide association study identifies distinct variants associated with pulmonary function among European and African ancestries from the UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 36641522

    ABSTRACT: Pulmonary function is an indicator of well-being, and pulmonary pathologies are the third major cause of death worldwide. We analysed the UK Biobank genome-wide association summary statistics of pulmonary function for Europeans and individuals of recent African descent to identify variants associated with the trait in the two ancestries. Here, we show 627 variants in Europeans and 3 in Africans associated with three pulmonary function parameters. In addition to the 110 variants in Europeans previously reported to be associated with phenotypes related to pulmonary function, we identify 279 novel loci, including an ISX intergenic variant rs369476290 on chromosome 22 in Africans. Remarkably, we find no shared variants among Africans and Europeans. Furthermore, enrichment analyses of

  • A saturated map of common genetic variants associated with human height - Unknown journal (n.d.) · Unknown authors · PubMed 36224396

    ABSTRACT: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation

  • An atlas of genetic influences on osteoporosis in humans and mice - Unknown journal (n.d.) · Unknown authors · PubMed 30598549

    ABSTRACT: Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound (eBMD) in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with eBMD, in ~1.2M individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds-ratio=58, p=10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice lacking target genes and found an increased abnormal skeletal phenotype frequency compared to 526

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