Table 2.
Single-nucleotide polymorphisms associated with the risk of abdominal aortic aneurysm validated in genome-wide association studies
| rs number | Nearest gene | OR (95% CI) | Proposed mechanisms |
|---|---|---|---|
| rs11591147 | PCSK9 | 1.58 (1.38, 1.82) | Degradation of the LDL receptor, thereby controlling circulating levels of LDL-C and inhibit VSMC proliferation and apoptosis45,50 |
| rs118039278 | LPA | 1.28 (1.21, 1.35) | Lipoprotein(a) concentrations45,51 |
| rs73149487 | ABHD16B | 1.26 (1.16, 1.36) | Endocannabinoid homeostasis45 |
| rs4007642 | CDKN2BAS1 | 1.21 (1.17, 1.25) | Long non-coding RNA controlling apoptosis and inflammation43,44,52 |
| rs964184 | ZNF259/APOA5 | 1.18 (1.14, 1.23) | Triglyceride, cholesterol, and glucose concentrations45,53 |
| rs429358 | APOE | 1.17 (1.12, 1.21) | Cholesterol transport45 |
| rs646776 | PSRC1-CELSR2-SORT1 | 1.15 (1.11, 1.20) | Cholesterol homeostasis45,48 |
| rs73015016 | LDLR | 1.15 (1.09, 1.21) | Cholesterol homeostasis44,45,47 |
| rs8124182 | MMP9 | 1.15 (1.10, 1.20) | Matrix remodeling44,45 |
| rs12730935 | IL-6R | 1.14 (1.10, 1.18) | Inflammation45,54–56 |
| rs7994761 | LINC00540 | 1.14 (1.09, 1.19) | Unknown44,45 |
| rs4936098 | ADAMTS8 | 1.13 (1.10, 1.16) | VSMC proliferation and AMPK activity45,57 |
| rs7025486 | DAB2IP | 1.12 (1.08, 1.16) | Cell apoptosis49,58 |
| rs55958997 | CHRNA3 | 1.12 (1.09, 1.16) | Nicotine dependance45 |
| rs4401144 | CTAGE1 | 1.11 (1.08, 1.14) | T cell function45 |
| rs12125521 | SMYD2 | 1.10 (1.06, 1.14) | Histone methylation44,45,59 |
| rs11172113 | LRP1 | 1.10 (1.06, 1.14) | VSMC MMP-9 clearance45,46,60 |
| rs2836411 | ERG | 1.10 (1.06, 1.14) | Inflammation44,45,61 |
| rs7255 | AC012065.7 | 1.10 (1.07, 1.13) | Long non-coding RNA expression45,62 |
| rs3176336 | CDKN1A | 1.10 (1.07, 1.13) | Cell cycle progression45 |
| rs10808546 | RP11-136O12.2/TRIB1 | 1.10 (1.07, 1.13) | Long non-coding RNA45 |
| rs1412445 | LIPA | 1.10 (1.07, 1.13) | Lipid homeostasis45,63 |
| rs10023907 | MEPE | 1.09 (1.06, 1.12) | Calcium-binding phosphoprotein involved in bone mineralisation45 |
| rs35254673 | CRISPLD2 | 1.09 (1.06, 1.13) | Unknown45 |
Single-nucleotide polymorphisms were selected based on genome-wide significance (P < 5 × 108) during discovery in one of nine previously published AAA genome-wide association studies and validation to be significantly associated with AAA in at least one other cohort including the largest and most recent study from the Million Veteran Program.44–46,48,49 The ORs and 95% CIs shown are all taken from the Million Veterans Program study to allow comparison of effect sizes.45 CDKN2BAS1, CDKN2B antisense RNA-1; IL-6R, interleukin-6 receptor; LDLR, low-density lipoprotein receptor; PSRC1-CELSR2-SORT1, proline/serine-rich coiled coil 1—cadherin, EGF LAG seven-pass G-type receptor 2-sortilin; MMP9, matrix metallopeptidase 9; SMYD2, SET And MYND domain containing 2; ERG, erythroblast transformation-specific related gene; LINC00540, long intergenic non–protein coding RNA-540; DAB2IP, disabled homolog 2 interacting protein; AC012065.7, clone-based Vega gene; CDKN1A, cyclin-dependent kinase inhibitor 1A; RP11-136O12.2/TRIB1, RP11-136O12.2 tribbles pseudokinase 1; LIPA, lysosomal acid lipase; ZNF259/APOA5, zinc finger protein/apolipoprotein A5; ADAMTS8, ADAM metallopeptidase with thrombospondin type 1 motif 8; CTAGE1, cutaneous T cell lymphoma-associated antigen 1; APOE, apolipoprotein E; PCSK9, proprotein convertase subtilisin/kexin type 9; LPA, lipoprotein(a); CHRNA3: cholinergic receptor nicotinic alpha 3 subunit; ABHD16B, abhydrolase domain containing 16B; VSMC, vascular smooth muscle cells; AMPK, AMP-activated protein kinase; LDL-C, low-density lipoprotein cholesterol; MEPE, matrix extracellular phosphoglycoprotein; CRISPLD2, cysteine-rich secretory protein LCCL domain containing 2.