Expressive

rs1037116 - PCSK6 - SNRPCP18

Magnitude 2.0 · 5 studies on file

Reported associations

  • Genome-wide characterization of circulating metabolic biomarkers - Nature (2024) · Karjalainen MK, Karthikeyan S, Oliver-Williams C, Sliz E, Allara E, Fung WT, Surendran P, Zhang W, Jousilahti P, Kristiansson K, Salomaa V, Goodwin M, Hughes DA, Boehnke M, Fernandes Silva L, Yin X, Mahajan A, Neville MJ, van Zuydam NR, de Mutsert R, Li-Gao R, Mook-Kanamori DO, Demirkan A, Liu J, Noordam R, Trompet S, Chen Z, Kartsonaki C, Li L, Lin K, Hagenbeek FA, Hottenga JJ, Pool R, Ikram MA, van Meurs J, Haller T, Milaneschi Y, Kähönen M, Mishra PP, Joshi PK, Macdonald-Dunlop E, Mangino M, Zierer J, Acar IE, Hoyng CB, Lechanteur YTE, Franke L, Kurilshikov A, Zhernakova A, Beekman M, van den Akker EB, Kolcic I, Polasek O, Rudan I, Gieger C, Waldenberger M, Asselbergs FW, Hayward C, Fu J, den Hollander AI, Menni C, Spector TD, Wilson JF, Lehtimäki T, Raitakari OT, Penninx BWJH, Esko T, Walters RG, Jukema JW, Sattar N, Ghanbari M, Willems van Dijk K, Karpe F, McCarthy MI, Laakso M, Järvelin MR, Timpson NJ, Perola M, Kooner JS, Chambers JC, van Duijn C, Slagboom PE, Boomsma DI, Danesh J, Ala-Korpela M, Butterworth AS, Kettunen J · PubMed 38448586

    ABSTRACT: Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associa

  • Metabolomic investigation of major depressive disorder identifies a potentially causal association with polyunsaturated fatty acids - Biological psychiatry (2023) · Davyson E, Shen X, Gadd DA, Bernabeu E, Hillary RF, McCartney DL, Adams M, Marioni R, McIntosh AM · PubMed 36764567

    ABSTRACT: Background: Metabolic differences have been reported between individuals with and without Major Depressive Disorder (MDD), but their consistency and causal relevance has been unclear. Methods: We conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in UK Biobank (N = 29, 757). We then applied 2-sample bidirectional Mendelian Randomisation (MR) and colocalization analysis to identify potentially causal relationships between each metabolite and MDD. Results: One hundred and ninety-one metabolites tested were significantly associated with MDD (PFDR < 0.05), which reduced to 129 after adjustment for likely confounders. Lower abundance of Omega-3 fatty acid measures and a higher Omega-6: Omega-3 ratio showed potentially causal effects on liabili

  • Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation - PLoS biology (2022) · Richardson TG, Leyden GM, Wang Q, Bell JA, Elsworth B, Davey Smith G, Holmes MV · 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

  • 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

  • A large electronic health record-based genome-wide study of serum lipids - Nature genetics (2019) · Hoffmann TJ, Theusch E, Haldar T, Ranatunga DK, Jorgenson E, Medina MW, Kvale MN, Kwok PY, Schaefer C, Krauss RM, Iribarren C, Risch N · PubMed 29507422

    ABSTRACT: A genome-wide association study of 94,674 multi-ethnic Kaiser Permanente members utilizing 478,866 longitudinal untreated serum lipid electronic-health-record-derived measurements (EHRs) empowered multiple novel findings: 121 new SNP associations (46 primary, 15 conditional, 60 in meta-analysis with Global Lipids Genetic Consortium); increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater in females for LDL, HDL, TC, the opposite for TG); differences in variance explained amongst non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistasis, with strong evidence for both at ABOxFUT2 for LDL; and eQTL tissue-enrichment implicating the liver, adipose, and pancreas. Utilizing EHR pharmacy dat

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