TY - JOUR
T1 - The impact of fatty acids biosynthesis on the risk of cardiovascular diseases in Europeans and East Asians
T2 - a Mendelian randomization study
AU - Borges, Maria-Carolina
AU - Haycock, Phillip
AU - Zheng, Jie
AU - Hemani, Gibran
AU - Howe, Laurence J.
AU - Schmidt, A. Floriaan
AU - Staley, James R.
AU - Lumbers, R. Thomas
AU - Henry, Albert
AU - Lemaitre, Rozenn N.
AU - Gaunt, Tom R.
AU - Holmes, Michael V.
AU - Davey Smith, George
AU - Hingorani, Aroon D.
AU - Lawlor, Deborah A.
N1 - weescheck
PY - 2022/11/28
Y1 - 2022/11/28
N2 - Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD 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 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 CVDs, 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 etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.
AB - Despite early interest, the evidence linking fatty acids to cardiovascular diseases (CVDs) remains controversial. We used Mendelian randomization to explore the involvement of polyunsaturated (PUFA) and monounsaturated (MUFA) fatty acids biosynthesis in the etiology of several CVD 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 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 CVDs, 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 etiology of CVDs and suggest LDL cholesterol as a potential mediating trait between PUFA biosynthesis and CVDs risk.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85142940906&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/35796550
U2 - https://doi.org/10.1093/hmg/ddac153
DO - https://doi.org/10.1093/hmg/ddac153
M3 - Article
C2 - 35796550
SN - 0964-6906
VL - 31
SP - 4034
EP - 4054
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 23
ER -