Borges, Maria-Carolina;
Haycock, Phillip;
Zheng, Jie;
Hemani, Gibran;
Howe, Laurence J;
Schmidt, A Floriaan;
Staley, James R;
... Lawlor, Deborah A; + view all
(2022)
The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians: a Mendelian randomization study.
Human Molecular Genetics
10.1093/hmg/ddac153.
(In press).
Preview |
Text
Lumbers_The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and east Asians_AAM.pdf Download (3MB) | Preview |
Abstract
Despite early interest, the evidence linking fatty acids to cardiovascular diseases remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the aetiology of several cardiovascular disease endpoints in up to 1 153 768 European (maximum 123 668 cases) and 212 453 East Asian (maximum 29 319 cases) ancestry individuals. As instruments, we selected single nucleotide polymorphisms (SNP) mapping to genes with well-known roles in PUFA (i.e. FADS1/2 and ELOVL2) and MUFA (i.e. SCD) biosynthesis. Our findings suggest that higher PUFA biosynthesis rate (proxied by rs174576 near FADS1/2) is related to higher odds of multiple cardiovascular diseases, particularly ischemic stroke, peripheral artery disease and venous thromboembolism, whereas higher MUFA biosynthesis rate (proxied by rs603424 near SCD) is related to lower odds of coronary artery disease among Europeans. Results were unclear for East Asians as most effect estimates were imprecise. By triangulating multiple approaches (i.e. uni-/multi-variable Mendelian randomization, a phenome-wide scan, genetic colocalization and within-sibling analyses), our results are compatible with higher low-density lipoprotein (LDL)-cholesterol (and possibly glucose) being a downstream effect of higher PUFA biosynthesis rate. Our findings indicate that PUFA and MUFA biosynthesis are involved in the aetiology of cardiovascular diseases and suggest LDL-cholesterol as a potential mediating trait between PUFA biosynthesis and cardiovascular diseases risk.
Archive Staff Only
 |
View Item |
