Phenotypic and Genetic Characterization of Lower LDL Cholesterol and Increased Type 2 Diabetes Risk in the UK Biobank
| Autor: | Amit Arora, Alexis C. Wood, Michelle Newell, Benjamin J. Renquist, Jose M. Ordovas, Jin Zhou, Yann C. Klimentidis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Blood Glucose medicine.medical_specialty Candidate gene Statin endocrine system diseases medicine.drug_class Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Type 2 diabetes 03 medical and health sciences 0302 clinical medicine Internal medicine Diabetes mellitus Hyperlipidemia Nonalcoholic fatty liver disease Internal Medicine medicine Humans Risk factor Biological Specimen Banks business.industry nutritional and metabolic diseases Genetics/Genomes/Proteomics/Metabolomics Odds ratio Cholesterol LDL medicine.disease United Kingdom 030104 developmental biology Diabetes Mellitus Type 2 lipids (amino acids peptides and proteins) business |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Although hyperlipidemia is traditionally considered a risk factor for type 2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL cholesterol (LDL-C) increases T2D risk. We thus sought to more comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that levels of circulating LDL-C were negatively associated with T2D prevalence (odds ratio 0.41 [95% CI 0.39, 0.43] per mmol/L unit of LDL-C), despite positive associations of circulating LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower circulating LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n = 431,167) and the Global Lipids Genetics Consortium (n = 188,577), and data on T2D from the Diabetes Genetics Replication and Meta-Analysis consortium (n = 898,130). We identified 31 loci associated with lower circulating LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this dual phenotype, and nine have previously been implicated in nonalcoholic fatty liver disease. These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C–lowering medications. |
| Databáze: | OpenAIRE |
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