التفاصيل البيبلوغرافية
| العنوان: |
Coronary artery disease, genetic risk and the metabolome in young individuals [version 1; peer review: 2 approved] |
| المؤلفون: |
Battram, T. (Thomas), Hoskins, L. (Luke), Hughes, D. A. (David A.), Kettunen, J. (Johannes), Ring, S. M. (Susan M.), Smith, G. D. (George Davey), Timpson, N. J. (Nicholas J.) |
| بيانات النشر: |
F1000 Research |
| سنة النشر: |
2019 |
| المجموعة: |
Jultika - University of Oulu repository / Oulun yliopiston julkaisuarkisto |
| مصطلحات موضوعية: |
ALSPAC, Childhood and adolescence, Coronary artery disease, Genetics, Metabolomics |
| الوصف: |
Background: Genome-wide association studies have identified genetic variants associated with coronary artery disease (CAD) in adults — the leading cause of death worldwide. It often occurs later in life, but variants may impact CAD-relevant phenotypes early and throughout the life-course. Cohorts with longitudinal and genetic data on thousands of individuals are letting us explore the antecedents of this adult disease. Methods: 149 metabolites, with a focus on the lipidome, measured using nuclear magnetic resonance (1H-NMR) spectroscopy, and genotype data were available from 5,905 individuals at ages 7, 15, and 17 years from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Linear regression was used to assess the association between the metabolites and an adult-derived genetic risk score (GRS) of CAD comprising 146 variants. Individual variant-metabolite associations were also examined. Results: The CAD-GRS associated with 118 of 149 metabolites (false discovery rate [FDR] < 0.05), the strongest associations being with low-density lipoprotein (LDL) and atherogenic non-LDL subgroups. Nine of 146 variants in the GRS associated with one or more metabolites (FDR < 0.05). Seven of these are within lipid loci: rs11591147 PCSK9, rs12149545 HERPUD1-CETP, rs17091891 LPL, rs515135 APOB, rs602633 CELSR2-PSRC1, rs651821 APOA5, rs7412 APOE-APOC1. All associated with metabolites in the LDL or atherogenic non-LDL subgroups or both including aggregate cholesterol measures. The other two variants identified were rs112635299 SERPINA1 and rs2519093 ABO. Conclusions: Genetic variants that influence CAD risk in adults are associated with large perturbations in metabolite levels in individuals as young as seven. The variants identified are mostly within lipid-related loci and the metabolites they associated with are primarily linked to lipoproteins. This knowledge could allow for preventative measures, such as increased monitoring of at-risk individuals and perhaps treatment earlier in life, to be ... |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| الإتاحة: |
http://urn.fi/urn:nbn:fi-fe2020040810760Test |
| حقوق: |
info:eu-repo/semantics/openAccess ; © 2018 Battram T et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.9A6A7A5C |
| قاعدة البيانات: |
BASE |
