Table 1.
Associations of genetically predicted plasma fatty acid levels with 15 cardiovascular diseases.
| CVD | Cases | Dataset | ALA (n = 1 SNP) | EPA (n = 2 SNPs) | DPA (n = 2 SNPs) | DHA (n = 1 SNP) | LA (n = 3 SNPs) | |||||
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |||
| Cerebrovascular disease | ||||||||||||
| Any ischemic stroke | 60 341 | MEGASTROKE | 0.93 (0.89, 0.98) | 0.002 | 1.06 (0.99, 1.13) | 0.081 | 1.04 (1.00, 1.07) | 0.060 | 1.11 (0.96, 1.27) | 0.153 | 0.96 (0.93, 0.99) | 0.006 |
| Large artery stroke | 6688 | MEGASTROKE | 0.82 (0.73, 0.91) | 2.11×10−4 | 1.17 (1.01, 1.36) | 0.035 | 1.13 (1.03, 1.23) | 0.007 | 1.28 (0.92, 1.78) | 0.142 | 0.86 (0.80, 0.93) | 8.61×10−5 |
| Small vessel stroke | 11 710 | MEGASTROKE | 0.94 (0.86, 1.03) | 0.203 | 1.13 (1.00, 1.27) | 0.060 | 1.07 (1.00, 1.15) | 0.084 | 0.85 (0.64, 1.12) | 0.240 | 0.99 (0.93, 1.05) | 0.746 |
| Cardioembolic stroke | 9006 | MEGASTROKE | 0.93 (0.85, 1.02) | 0.141 | 1.04 (0.91, 1.18) | 0.567 | 1.04 (0.97, 1.12) | 0.284 | 1.05 (0.80, 1.40) | 0.715 | 0.95 (0.89, 1.02) | 0.149 |
| Transient ischemic attack | 3962 | UK Biobank | 0.92 (0.82, 1.03) | 0.158 | 1.12 (0.95, 1.32) | 0.174 | 1.05 (0.96, 1.15) | 0.317 | 1.09 (0,76, 1.57) | 0.631 | 0.96 (0.88, 1.04) | 0.297 |
| Intracerebral hemorrhage | 1064 | UK Biobank | 1.05 (0.84, 1.32) | 0.652 | 0.90 (0.66, 1.23) | 0.506 | 1.00 (0.84, 1.19) | 0.993 | 0.74 (0.37, 1.48) | 0.387 | 1.03 (0.88, 1.20) | 0.737 |
| Subarachnoid hemorrhage | 1084 | UK Biobank | 1.06 (0.85, 1.33) | 0.599 | 1.07 (0.79, 1.46) | 0.668 | 1.06 (0.89, 1.26) | 0.549 | 0.47 (0.23, 0.93) | 0.030 * | 1.08 (0.93, 1.27) | 0.317 |
| Heart disease | ||||||||||||
| Coronary artery disease | 60 801 | CARDIoGRAMplusC4D | 0.95 (0.90, 0.99) | 0.027 | 1.08 (1.01, 1.15) | 0.038 | 1.04 (1.00, 1.08) | 0.045 | 1.00 (0.86, 1.16) | 1.000 | 0.96 (0.92, 0.99) | 0.011 |
| Heart failure | 6712 | UK Biobank | 1.03 (0.94, 1.13) | 0.533 | 1.01 (0.89, 1.15) | 0.866 | 0.99 (0.92, 1.06) | 0.762 | 0.90 (0.68, 1.19) | 0.463 | 1.02 (0.96, 1.08) | 0.604 |
| Atrial fibrillation | 65 446 | AFGen | 0.97 (0.94, 1.01) | 0.158 | 1.05 (0.99, 1.10) | 0.085 | 1.02 (0.99, 1.05) | 0.265 | 0.99 (0.88, 1.11) | 0.813 | 0.97 (0.94, 0.99) | 0.009 |
| Aortic valve stenosis | 2244 | UK Biobank | 0.81 (0.69, 0.94) | 0.006 | 1.32 (1.07, 1.64) | 0.011 | 1.17 (1.04, 1.33) | 0.011 | 0.93 (0.58, 1.51) | 0.779 | 0.88 (0.79, 0.98) | 0.024 |
| Abdominal aortic aneurysm | 1094 | UK Biobank | 0.78 (0.62, 0.97) | 0.025 | 1.41 (1.04, 1.92) | 0.027 | 1.26 (1.06, 1.50) | 0.010 | 0.60 (0.30, 1.19) | 0.140 | 0.87 (0.74, 1.02) | 0.077 |
| Thoracic aortic aneurysm | 347 | UK Biobank | 0.85 (0.57, 1.25) | 0.406 | 1.04 (0.60, 1.79) | 0.895 | 1.05 (0.77, 1.43) | 0.761 | 1.52 (0.45, 5.14) | 0.504 | 0.95 (0.72, 1.25) | 0.708 |
| Vessel disease | ||||||||||||
| Peripheral arterial disease | 3415 | UK Biobank | 0.90 (0.79, 1.02) | 0.096 | 1.18 (1.00, 1.41) | 0.058 | 1.09 (0.99, 1.21) | 0.085 | 0.93 (0.63, 1.37) | 0.696 | 0.93 (0.85, 1.01) | 0.087 |
| Venous thromboembolism | 15 602 | UK Biobank | 0.88 (0.82, 0.93) | 4.39×10−5 | 1.13 (1.03, 1.23) | 0.007 | 1.08 (1.03, 1.13) | 0.003 | 1.14 (0.93, 1.38) | 0.202 | 0.92 (0.88, 0.96) | 1.95×10−4 |
| CVD | Cases | Dataset | AA (n = 2 SNPs) | POA (n = 4 SNPs) | OA (n = 1 SNP) | PA (n = 1 SNP) | SA (n = 3 SNPs) | |||||
| OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | OR (95% CI) | P value | |||
| Cerebrovascular disease | ||||||||||||
| Any ischemic stroke | 60 341 | MEGASTROKE | 1.03 (1.01, 1.06) | 0.002 | 0.97 (0.90, 1.05) | 0.422 | 0.87 (0.80, 0.95) | 0.002 | 0.90 (0.77, 1.05) | 0.164 | 1.12 (1.04, 1.21) | 0.003 |
| Large artery stroke | 6688 | MEGASTROKE | 1.10 (1.04, 1.15) | 3.34×10−4 | 0.82 (0.68, 0.98) | 0.031 | 0.68 (0.55, 0.85) | 5.34×10−4 | 0.90 (0.62, 1.32) | 0.591 | 1.35 (1.12, 1.61) | 0.001 |
| Small vessel stroke | 11 710 | MEGASTROKE | 1.03 (0.99, 1.08) | 0.136 | 0.95 (0.84, 1.09) | 0.464 | 0.89 (0.75, 1.06) | 0.196 | 0.86 (0.62, 1.18) | 0.345 | 1.19 (1.03, 1.39) | 0.021 |
| Cardioembolic stroke | 9006 | MEGASTROKE | 1.04 (0.99, 1.08) | 0.099 | 0.90 (0.76, 1.06) | 0.210 | 0.84 (0.69, 1.01) | 0.057 | 0.98 (0.71, 1.34) | 0.874 | 1.08 (0.92, 1.26) | 0.344 |
| Transient ischemic attack | 3962 | UK Biobank | 1.04 (0.99, 1.10) | 0.144 | 0.96 (0.77, 1.19) | 0.687 | 0.84 (0.66, 1.06) | 0.139 | 1.05 (0.70, 1.58) | 0.805 | 1.11 (0.91, 1.36) | 0.285 |
| Intracerebral hemorrhage | 1064 | UK Biobank | 0.97 (0.88, 1.08) | 0.605 | 0.88 (0.59, 1.32) | 0.526 | 1.15 (0.73, 1.82) | 0.535 | 1.32 (0.61, 2.89) | 0.482 | 0.81 (0.56, 1.19) | 0.281 |
| Subarachnoid hemorrhage | 1084 | UK Biobank | 0.98 (0.88, 1.08) | 0.673 | 1.18 (0.78, 1.77) | 0.441 | 1.20 (0.76, 1.87) | 0.437 | 0.78 (0.36, 1.69) | 0.528 | 1.19 (0.82, 1.73) | 0.372 |
| Heart disease | ||||||||||||
| Coronary artery disease | 60 801 | CARDIoGRAMplusC4D | 1.02 (1.00, 1.05) | 0.042 | 0.89 (0.82, 0.97) | 0.008 | 0.90 (0.81, 0.99) | 0.036 | 1.03 (0.88, 1.22) | 0.691 | 1.02 (0.94, 1.11) | 0.620 |
| Heart failure | 6712 | UK Biobank | 0.99 (0.95, 1.03) | 0.535 | 0.89 (0.76, 1.05) | 0.180 | 1.06 (0.89, 1.27) | 0.524 | 0.93 (0.68, 1.27) | 0.631 | 1.02 (0.87, 1.18) | 0.825 |
| Atrial fibrillation | 65 446 | AFGen | 1.01 (1.00, 1.03) | 0.180 | 1.04 (0.97, 1.11) | 0.262 | 0.95 (0.88, 1.02) | 0.137 | 1.12 (0.98, 1.28) | 0.087 | 1.01 (0.95, 1.08) | 0.748 |
| Aortic valve stenosis | 2244 | UK Biobank | 1.11 (1.03, 1.19) | 0.004 | 0.80 (0.60, 1.07) | 0.128 | 0.66 (0.48, 0.90) | 0.008 | 0.91 (0.53, 1.55) | 0.724 | 1.33 (1.03, 1.73) | 0.031 |
| Abdominal aortic aneurysm | 1094 | UK Biobank | 1.13 (1.02, 1.25) | 0.022 | 0.88 (0.59, 1.32) | 0.537 | 0.61 (0.39, 0.96) | 0.032 | 1.39 (0.64, 2.99) | 0.405 | 1.23 (0.85, 1.78) | 0.282 |
| Thoracic aortic aneurysm | 347 | UK Biobank | 1.08 (0.90, 1.30) | 0.388 | 1.07 (0.52, 2.21) | 0.852 | 0.70 (0.32, 1.55) | 0.376 | 1.03 (0.26, 4.04) | 0.965 | 1.26 (0.65, 2.44) | 0.501 |
| Vessel disease | ||||||||||||
| Peripheral arterial disease | 3415 | UK Biobank | 1.05 (0.99, 1.11) | 0.104 | 0.92 (073, 1.16) | 0.493 | 0.82 (0.64, 1.06) | 0.135 | 1.06 (0.68, 1.64) | 0.803 | 1.14 (0.92, 1.40) | 0.242 |
| Venous thromboembolism | 15 602 | UK Biobank | 1.07 (1.04, 1.10) | 1.90×10−5 | 0.85 (0.76, 0.95) | 0.006 | 0.77 (0.68, 0.87) | 4.09×10−5 | 0.92 (0.74, 1.14) | 0.446 | 1.22 (1.10, 1.36) | 2.32×10−4 |
AA indicates arachidonic acid; ALA, α-linolenic acid; CVD, cardiovascular disease; CI, confidence interval; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; LA, linoleic acid; OA, oleic acid; OR, odds ratio; PA, palmitic acid; POA, palmitoleic acid; SA, stearic acid; SNP, single-nucleotide polymorphism.* The significance remained in the sensitivity analysis excluding SNPs in or close to the FADS1 gene.