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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Interrogating causal pathways linking genetic variants, small molecule metabolites, and circulating lipids
Genome Medicine, Volume 6, No. 3, Article 25, Year 2014
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Description
Background: Emerging technologies based on mass spectrometry or nuclear magnetic resonance enable the monitoring of hundreds of small metabolites from tissues or body fluids. Profiling of metabolites can help elucidate causal pathways linking established genetic variants to known disease risk factors such as blood lipid traits.Methods: We applied statistical methodology to dissect causal relationships between single nucleotide polymorphisms, metabolite concentrations, and serum lipid traits, focusing on 95 genetic loci reproducibly associated with the four main serum lipids (total-, low-density lipoprotein-, and high-density lipoprotein- cholesterol and triglycerides). The dataset used included 2,973 individuals from two independent population-based cohorts with data for 151 small molecule metabolites and four main serum lipids. Three statistical approaches, namely conditional analysis, Mendelian randomization, and structural equation modeling, were compared to investigate causal relationship at sets of a single nucleotide polymorphism, a metabolite, and a lipid trait associated with one another.Results: A subset of three lipid-associated loci (FADS1, GCKR, and LPA) have a statistically significant association with at least one main lipid and one metabolite concentration in our data, defining a total of 38 cross-associated sets of a single nucleotide polymorphism, a metabolite and a lipid trait. Structural equation modeling provided sufficient discrimination to indicate that the association of a single nucleotide polymorphism with a lipid trait was mediated through a metabolite at 15 of the 38 sets, and involving variants at the FADS1 and GCKR loci.Conclusions: These data provide a framework for evaluating the causal role of components of the metabolome (or other intermediate factors) in mediating the association between established genetic variants and diseases or traits. © 2014 Shin et al.; licensee BioMed Central Ltd.
Authors & Co-Authors
Shin, So-youn
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Bristol
University of Bristol
Petersen, Ann Kristin
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Wahl, Simone
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Oberschleissheim
Deutsches Zentrum Für Diabetesforschung
Zhai, Guangju
United Kingdom, London
King's College London
Canada, St John's
Memorial University of Newfoundland, Faculty of Medicine
Römisch-Margl, Werner
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Small, Kerrin S.
United Kingdom, London
King's College London
Döring, Angela
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Kato, Bernet Sekasanvu
United Kingdom, London
King's College London
United Kingdom, London
Imperial College London
Peters, Annette Michael
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Grundberg, Elin
Canada, Montreal
Mcgill Faculty of Medicine and Health Sciences
Canada, Montreal
Université Mcgill
Prehn, Cornelia
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Wang-Sattler, Rui
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Wichmann, Heinz-Erich Erich
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Ludwig-maximilians-universität München
Germany, Munich
Klinikum Der Universität München
de Angelis, Martin Hrabé
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Technische Universität München
Illig, Thomas
Germany, Hannover
Hannover Medical School
Adamski, Jerzy
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Technische Universität München
Deloukas, Panos
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, London
Barts and the London School of Medicine and Dentistry
Saudi Arabia, Jeddah
King Abdulaziz University
Spector, Tim David
United Kingdom, London
King's College London
Suhre, Karsten
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Qatar, Doha
Weill Cornell Medicine-qatar
Gieger, Christian
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Soranzo, Nicole
United Kingdom, Hinxton
Wellcome Sanger Institute
Statistics
Citations: 21
Authors: 21
Affiliations: 16
Identifiers
Doi:
10.1186/gm542
e-ISSN:
1756994X
Research Areas
Cancer
Genetics And Genomics
Study Design
Randomised Control Trial
Cross Sectional Study
Cohort Study