ArticlemedRxiv : the preprint server for health sciences2024
Genome-wide association studies and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating polyunsaturated, monounsaturated, and saturated fatty acids.
Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Previous genome-wide association studies (GWAS) have identified genetic loci associated with the circulating levels of FAs, but the biological mechanisms of these genetic associations remain largely unexplored. Here, we conducted GWAS to identify additional genetic loci for 19 circulating fatty acid (FA) traits in UK Biobank participants of European ancestry (N = 239,268) and five other ancestries (N = 508 - 4,663). We leveraged the GWAS findings to characterize genetic correlations and colocalized regions among FAs, explore sex differences, examine FA loci influenced by lipoprotein metabolism, and apply statistical fine-mapping to pinpoint putative causal variants. We integrated GWAS signals with multi-omics quantitative trait loci (QTL) to reveal intermediate molecular phenotypes mediating the associations between the genetic loci and FA levels. Altogether, we identified 215 significant loci for polyunsaturated fatty acids (PUFAs)-related traits in European participants, 163 loci for monounsaturated fatty acids (MUFAs)-related traits, and 119 loci for saturated fatty acids (SFAs)-related traits, including 70, 61, and 54 novel loci, respectively. A novel locus for total FAs, the percentage of omega-6 PUFAs in total FAs, and total MUFAs (around genes
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