Expressive

rs111366116 - ARL15

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

  • 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function - Unknown journal (n.d.) · Unknown authors · PubMed 28452372

    ABSTRACT: HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SN

  • Testosterone and socioeconomic position: Mendelian randomization in 306,248 men and women in UK Biobank - Unknown journal (n.d.) · Unknown authors · PubMed 34321204

    ABSTRACT: Mendelian randomization suggests circulating testosterone does not meaningfully affect men's socioeconomic position. Men with more advantaged socioeconomic position (SEP) have been observed to have higher levels of testosterone. It is unclear whether these associations arise because testosterone has a causal impact on SEP. In 306,248 participants of UK Biobank, we performed sex-stratified genome-wide association analysis to identify genetic variants associated with testosterone. Using the identified variants, we performed Mendelian randomization analysis of the influence of testosterone on socioeconomic position, including income, employment status, neighborhood-level deprivation, and educational qualifications; on health, including self-rated health and body mass index; and on

  • Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation - Unknown journal (n.d.) · Unknown authors · PubMed 35213538

    ABSTRACT: Large-scale molecular profiling and genotyping provide a unique opportunity to systematically compare the genetically predicted effects of therapeutic targets on the human metabolome. We firstly constructed genetic risk scores for 8 drug targets on the basis that they primarily modify low-density lipoprotein (LDL) cholesterol (HMGCR, PCKS9, and NPC1L1), high-density lipoprotein (HDL) cholesterol (CETP), or triglycerides (APOC3, ANGPTL3, ANGPTL4, and LPL). Conducting mendelian randomisation (MR) provided strong evidence of an effect of drug-based genetic scores on coronary artery disease (CAD) risk with the exception of ANGPTL3. We then systematically estimated the effects of each score on 249 metabolic traits derived using blood samples from an unprecedented sample size of up to

  • Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis - Unknown journal (n.d.) · Unknown authors · PubMed 31015462

    ABSTRACT: Chronic kidney disease (CKD) is a growing health burden currently affecting 10-15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analy

  • Blood metabolic biomarkers and colorectal cancer risk: results from large prospective cohort and Mendelian randomisation analyses - Unknown journal (n.d.) · Unknown authors · PubMed 40307439

    ABSTRACT: Background Emerging evidence suggests metabolic dysregulation may contribute to colorectal cancer (CRC) aetiology. We aimed to identify pre-diagnostic metabolic biomarkers for CRC risk in 230,420 UK Biobank participants. Methods Nuclear magnetic resonance spectroscopy was used to quantify 249 metabolic biomarkers in plasma samples collected at baseline. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CIs) for associations of metabolic biomarkers with CRC risk after adjusting for potential confounders. To infer the potential causality of biomarkers that were associated with CRC independent of the others, we performed genome-wide association analyses among 199,732 UK Biobank participants of European ancestry to identify biomarker-as

  • GWAS and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating fatty acids - Unknown journal (n.d.) · Unknown authors · PubMed 40545721

    ABSTRACT: Summary Previous genome-wide association studies (GWAS) have identified genetic loci associated with the circulating levels of fatty acids (FAs), but the biological mechanisms of these genetic associations remain largely unexplored. Here, we conducted GWAS to identify additional genetic loci for 19 circulating FA traits in UK Biobank participants of European ancestry (n = 239,268) and five other ancestries (n = 508-4,663). We leveraged the GWAS findings to characterize genetic correlations and colocalized regions among FAs, explore sex differences, examine FA loci influenced by lipoprotein metabolism, and apply statistical fine-mapping to pinpoint putative causal variants. We integrated GWAS signals with multi-omics quantitative trait loci (QTL) to reveal intermediate molecular

  • Genetic analyses implicate complex links between adult testosterone levels and health and disease - Unknown journal (n.d.) · Unknown authors · PubMed 36653534

    ABSTRACT: Background Testosterone levels are linked with diverse characteristics of human health, yet, whether these associations reflect correlation or causation remains debated. Here, we provide a broad perspective on the role of genetically determined testosterone on complex diseases in both sexes. Methods Leveraging genetic and health registry data from the UK Biobank and FinnGen (total N = 625,650), we constructed polygenic scores (PGS) for total testosterone, sex-hormone binding globulin (SHBG) and free testosterone, associating these with 36 endpoints across different disease categories in the FinnGen. These analyses were combined with Mendelian Randomization (MR) and cross-sex PGS analyses to address causality. Results We show testosterone and SHBG levels are intricately tied t

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