Expressive

rs1049742 - AOC1

Magnitude 2.2 · 8 studies on file

Reported associations

  • Body surface area is a potential obesity index: Its genetic determination and its causality for later-life diseases. - Obesity (Silver Spring, Md.) (2022) · Yu XH, Cao RR, Yang YQ, Deng FY, Bo L, Lei SF · PubMed 36502284

    This study aimed to identify novel genetic factors that contribute to body surface area (BSA) and explore its relationship with complex traits and diseases. Based on more than 330,000 European individuals in the UK Biobank, the first large-scale genome-wide association study for BSA was performed. Comprehensive genetic analysis and enrichment analysis were then performed to explore the biological function of the identified loci. The genetic correlations and causal associations between BSA and other anthropometry parameters, early growth indices, and later-life diseases, respectively, were assessed by complex genetic approaches. Genome-wide association study analysis identified a total of 456 conditionally independent single-nucleotide polymorphism mapping genes with known functions in the

  • A Genome-wide Association Study Discovers 46 Loci of the Human Metabolome in the Hispanic Community Health Study/Study of Latinos. - American journal of human genetics (2020) · Feofanova EV, Chen H, Dai Y, Jia P, Grove ML, Morrison AC, Qi Q, Daviglus M, Cai J, North KE, Laurie CC, Kaplan RC, Boerwinkle E, Yu B · PubMed 33031748

    Variation in levels of the human metabolome reflect changes in homeostasis, providing a window into health and disease. The genetic impact on circulating metabolites in Hispanics, a population with high cardiometabolic disease burden, is largely unknown. We conducted genome-wide association analyses on 640 circulating metabolites in 3,926 Hispanic Community Health Study/Study of Latinos participants. The estimated heritability for 640 metabolites ranged between 0%-54% with a median at 2.5%. We discovered 46 variant-metabolite pairs (p value < 1.2 × 10 , minor allele frequency ≥ 1%, proportion of variance explained [PEV] mean = 3.4%, PEV = 1%-22%) with generalized effects in two population-based studies and confirmed 301 known locus-metabolite associations. Half of the identified varian

  • 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%

  • Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases - Unknown journal (n.d.) · Unknown authors · PubMed 36635386

    ABSTRACT: Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci; and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian Randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured orotate level in a separate co

  • Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations - Unknown journal (n.d.) · Unknown authors · PubMed 37253714

    ABSTRACT: Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs a

  • Mapping the serum proteome to neurological diseases using whole genome sequencing - Unknown journal (n.d.) · Unknown authors · PubMed 34857772

    ABSTRACT: Despite the increasing global burden of neurological disorders, there is a lack of effective diagnostic and therapeutic biomarkers. Proteins are often dysregulated in disease and have a strong genetic component. Here, we carry out a protein quantitative trait locus analysis of 184 neurologically-relevant proteins, using whole genome sequencing data from two isolated population-based cohorts (N = 2893). In doing so, we elucidate the genetic landscape of the circulating proteome and its connection to neurological disorders. We detect 214 independently-associated variants for 107 proteins, the majority of which (76%) are cis-acting, including 114 variants that have not been previously identified. Using two-sample Mendelian randomisation, we identify causal associations between s

  • Genetics of 35 blood and urine biomarkers in the UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 33462484

    ABSTRACT: Clinical laboratory tests are a critical component of the continuum of care. We evaluate the genetic basis of 35 blood and urine laboratory measurements in the UK Biobank (n=363,228 individuals). We identify 1,857 loci associated with at least one trait, containing 3,374 fine-mapped associations, and additional sets of large-effect (> 0.1 sd) protein-altering, HLA, and copy-number variant associations. Through Mendelian Randomization analysis, we discover 51 causal relationships, including previously known agonistic effects of urate on gout and cystatin C on stroke. Finally, we develop polygenic risk scores for each biomarker and built 'multi-PRS' models for diseases using 35 PRSs simultaneously, which improved chronic kidney disease, type 2 diabetes, gout, and alcoholic cirr

  • Rare and common genetic determinants of metabolic individuality and their effects on human health - Unknown journal (n.d.) · Unknown authors · PubMed 36357675

    ABSTRACT: Garrod's concept of 'chemical individuality' has contributed to comprehension of the molecular origins of human diseases. Untargeted high-throughput metabolomic technologies provide an in-depth snapshot of human metabolism at scale. We studied the genetic architecture of the human plasma metabolome using 913 metabolites assayed in 19,994 individuals and identified 2,599 variant-metabolite associations (P < 1.25 × 10−11) within 330 genomic regions, with rare variants (minor allele frequency ≤ 1%) explaining 9.4% of associations. Jointly modeling metabolites in each region, we identified 423 regional, co-regulated, variant-metabolite clusters called genetically influenced metabotypes. We assigned causal genes for 62.4% of these genetically influenced meta

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