Genome-wide Association Study of Complex Lipid Species: Results from the population-based Rhineland Study
Landstra, E. N.; Imtiaz, M. A.; Talevi, V.; Eichelmann, F.; Schulze, M. B.; Aziz, N. A.; Breteler, M. M. B.
Show abstract
The human lipidome comprises numerous complex lipids, dysregulation of which can contribute to the pathogenesis of a wide range of diseases. Despite the high heritability of parts of the lipidome, the genetic architecture of many circulating lipid species and their structure remains mostly unknown. Thus, we performed genome-wide association studies on 970 lipid species and 267 fatty acid composite measures using samples from the population-based Rhineland Study (n=6,096). We validated our findings using corresponding data from two other independent cohorts, including FinnGen (n=7,266) and EPIC-Potsdam (n=1,188). Out of 217 lead genomic loci, we found 135 to be novel, such as FDFT1. Using mendelian randomization and individual-level gene expression data, we identified five possible causal associations between candidate genes and corresponding lipid species, including FDFT1-diacylglycerol (16:0/18:0). Our findings provide new insights into the intricate genetic underpinnings of lipid metabolism, which may facilitate risk stratification and discovery of new therapeutic targets.
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