A phenome-wide association study of a lipoprotein associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults
| Autor: | Millwood, Iona Y, Bennett, Derrick A, Walters, Robin G, Clarke, Robert, Waterworth, Dawn, Johnson, Toby, Chen, Yiping, Yang, Ling, Guo, Yu, Bian, Zheng, Hacker, Alex, Yeo, Astrid, Parish, Sarah, Hill, Michael R, Chissoe, Stephanie, Peto, Richard, Cardon, Lon, Collins, Rory, Li, Liming, Chen, Zhengming |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male China genetic association Genotype Lp-PLA2 vascular disease phenome-wide Middle Aged Polymorphism Single Nucleotide Logistic Models Phenotype Asian People Mendelian Randomization International Classification of Diseases Risk Factors 1-Alkyl-2-acetylglycerophosphocholine Esterase Linear Models Humans Female Genetic Predisposition to Disease Prospective Studies Vascular Diseases Aged |
| Zdroj: | International Journal of Epidemiology |
| ISSN: | 1464-3685 7686-3441 |
| Popis: | Background Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been implicated in development of atherosclerosis, however, recent randomised trials of Lp-PLA2 inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically-determined lower Lp-PLA2. Methods PLA2G7V279F (rs76863441) was genotyped in 91 428 individuals randomly-selected from the China Kadoorie Biobank of 0.5M participants recruited in 2004-2008from 10 regions of China, with seven years follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. Results PLA2G7V279F frequency was 5% overall (range 3-7% by region), and 9,691 (11%) participants had at least one loss-of-function variant. V279F was not associatedwith baseline blood pressure, adiposity, blood glucose, or lung function. V279F was not associated with major vascular events (7141 events; OR=0.98 per F variant, 95% CI 0.90-1.06), or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) andstroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. Conclusions Lifelong lower Lp-PLA2 activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning. |
| Databáze: | OpenAIRE |
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