rs116483731 - SPDL1

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

• Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses - Unknown journal (n.d.) · Unknown authors · PubMed 34226706

  ABSTRACT: Exome association studies to date have generally been underpowered to systematically evaluate the phenotypic impact of very rare coding variants. We leveraged extensive haplotype sharing between 49,960 exome-sequenced UK Biobank participants and the remainder of the cohort (total N~500K) to impute exome-wide variants with accuracy R2>0.5 down to minor allele frequency (MAF) ~0.00005. Association and fine-mapping analyses of 54 quantitative traits identified 1,189 significant associations (P<5 x 10−8) involving 675 distinct rare protein-altering variants (MAF<0.01) that passed stringent filters for likely causality. Across all traits, 49% of associations (578/1,189) occurred in genes with two or more hits; follow-up analyses of these genes identified allelic series containing up

• Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis - Unknown journal (n.d.) · Unknown authors · PubMed 33758299

  ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a fatal disorder characterised by progressive, destructive lung scarring. Despite substantial progress, the genetic determinants of this disease remain incompletely defined. Using whole genome and whole exome sequencing data from 752 individuals with sporadic IPF and 119,055 UK Biobank controls, we performed a variant-level exome-wide association study (ExWAS) and gene-level collapsing analyses. Our variant-level analysis revealed a novel association between a rare missense variant in SPDL1 and IPF (NM_017785.5:g.169588475 G > A p.Arg20Gln; p = 2.4 × 10−7, odds ratio = 2.87, 95% confidence interval: 2.03-4.07). This signal was independently replicated in the FinnGen cohort, which contains 1028 cases and 196,986 controls

• Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases - Unknown journal (n.d.) · Unknown authors · PubMed 41644669

  ABSTRACT: Thyroid diseases are common and highly heritable. We performed a meta-analysis of genome-wide association studies from 19 biobanks for five thyroid diseases: thyroid cancer (ThC), benign nodular goiter, Graves' disease, lymphocytic thyroiditis and primary hypothyroidism. We analyzed genetic association data from ~2.9 million genomes and identified 313 known and 570 new independent loci linked to thyroid diseases. We discovered genetic correlations between ThC, benign nodular goiter and autoimmune thyroid diseases (rg = 0.16-0.97). Telomere maintenance genes contributed to benign and malignant thyroid nodular disease risk, whereas cell cycle, DNA repair and damage response genes were associated with ThC. We propose a paradigm that explains genetic predisposition to benign

• 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

• 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

• Using human genetics to understand the disease impacts of testosterone in men and women - Unknown journal (n.d.) · Unknown authors · PubMed 32042192

  ABSTRACT: Testosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate the genetic determinants of testosterone levels are substantially different between sexes, and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1-standard deviation higher testosterone increases the risks of Type 2 diabetes (T2D) (OR=1.37 [1.22-1.53]) and polycystic ovary syndrome (OR=1.51 [1.33-1.72]) in

• Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants - Unknown journal (n.d.) · Unknown authors · PubMed 37945903

  [INTRO] Introduction [INTRO] The transferability and clinical value of genetic risk scores (GRS) across populations remains limited due to an imbalance in genetic studies across ancestrally diverse populations. We conducted a multi-ancestry genome-wide association study (GWAS) of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian, and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer GWAS. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation (SD)) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a gre

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