Expressive

rs10260816 - IGFBP3 - FTLP15

Magnitude 2.2 · 8 studies on file

Reported associations

  • Sex-specific genetic architecture of blood pressure. - Nature medicine (2024) · Yang ML, Xu C, Gupte T, Hoffmann TJ, Iribarren C, Zhou X, Ganesh SK · PubMed 38459180

    The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (P ≤ 5 × 10 ; P > 5 × 10 ) and 142 were male-specific (P ≤ 5 × 10 ; P > 5 × 10 ); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1. Analyses of gene-by-sex interactions and sexually dimorphic effects identified four genomic regions, showing female-specific associations with diastolic BP or pulse pressure, including the chromosome 13q34-COL4A1/

  • The Genetic Determinants of Aortic Distention. - Journal of the American College of Cardiology (2023) · Pirruccello JP, Rämö JT, Choi SH, Chaffin MD, Kany S, Nekoui M, Chou EL, Jurgens SJ, Friedman SF, Juric D, Stone JR, Batra P, Ng K, Philippakis AA, Lindsay ME, Ellinor PT · PubMed 37019578

    As the largest conduit vessel, the aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distention and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease. In this study, we sought to discover epidemiologic correlates and genetic determinants of aortic distensibility and strain. We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images and calculated aortic distensibility and strain in 42,342 UK Biobank participants. Descending aortic distensibility was inversely associated with future incidence o

  • 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

  • Assessing the predictive efficacy of European-based systolic blood pressure polygenic risk scores in diverse Brazilian cohorts - Unknown journal (n.d.) · Unknown authors · PubMed 39548300

    ABSTRACT: Despite the identification of numerous genetic variants affecting SBP in European populations, their applicability in admixed populations remains unclear. This study evaluates the predictive efficacy of a systolic blood pressure (SBP) polygenic risk score (PRS), derived from the UK Biobank data, in two Brazilian cohorts. We analyzed 944 K genetic variants consistent across an independent UK Biobank dataset, Brazilian cohorts, and HapMap database. Results show a significant association between increased PRS and SBP, as well as hypertension, in each study groups analyzed. An increase of one standard deviation in the PRS showed a significant association with SBP (β [95% CI] (mmHg) = 5.2 [5.1-5.3], 2.8 [2.1-3.5] and 2.6 [2.2-3.0]) and hypertension (odds ratio (OR) [95% CI

  • The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study - Unknown journal (n.d.) · Unknown authors · PubMed 33097823

    ABSTRACT: Appendicular lean mass (ALM) is a heritable trait associated with loss of lean muscle mass and strength, or sarcopenia, but its genetic determinants are largely unknown. Here we conducted a genome-wide association study (GWAS) with 450,243 UK Biobank participants to uncover its genetic architecture. A total of 1059 conditionally independent variants from 799 loci were identified at the genome-wide significance level (p < 5 × 10−9), all of which were also significant at p < 5 × 10-5 in both sexes. These variants explained ~15.5% of the phenotypic variance, accounting for more than one quarter of the total ~50% GWAS-attributable heritability. There was no difference in genetic effect between sexes or among different age strata. Heritability was enriched in cer

  • Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program - Unknown journal (n.d.) · Unknown authors · PubMed 39024449

    ABSTRACT: INTRODUCTION: Findings from genome-wide association studies (GWASs) have provided foundational knowledge of the genetic basis of disease, facilitating precision approaches for prevention and treatment. Current GWAS results are limited by underrepresentation of individuals from diverse populations, leading to concerns with generalizability regarding our knowledge of the relationships between genes, traits, and disease. The Department of Veterans Affairs (VA) Million Veteran Program (MVP), one of the largest US-based biobanks, addresses this need; 29% of MVP comprises individuals genetically similar to African (AFR), Admixed American (AMR), and East Asian (EAS) reference populations. With over 635,000 participants and more than 44.3M genotyped variants linked with detailed phenotyp

  • High Blood Pressure and Intraocular Pressure: A Mendelian Randomization Study - Unknown journal (n.d.) · Unknown authors · PubMed 35762941

    ABSTRACT: Purpose To test for causality with regard to the association between blood pressure (BP) and intraocular pressure (IOP) and glaucoma. Methods Single nucleotide polymorphisms (SNPs) associated with BP were identified in a genome-wide association study (GWAS) meta-analysis of 526,001 participants of European ancestry. These SNPs were used to assess the BP versus IOP relationship in a distinct sample (n = 70,832) whose corneal-compensated IOP (IOPcc) was measured. To evaluate the BP versus primary open-angle glaucoma (POAG) relationship, additional Mendelian randomization (MR) analyses were conducted using published GWAS summary statistics. Results Observational analysis revealed a linear relationship between BP traits and IOPcc, with a +0.28 mm Hg increase in IOPcc per 10-mm Hg inc

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