Title | Whole-genome sequencing uncovers two loci for coronary artery calcification and identifies ARSE as a regulator of vascular calcification. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | de Vries, PS, Conomos, MP, Singh, K, Nicholson, CJ, Jain, D, Hasbani, NR, Jiang, W, Lee, S, Cardenas, CLLino, Lutz, SM, Wong, D, Guo, X, Yao, J, Young, EP, Tcheandjieu, C, Hilliard, AT, Bis, JC, Bielak, LF, Brown, MR, Musharoff, S, Clarke, SL, Terry, JG, Palmer, ND, Yanek, LR, Xu, H, Heard-Costa, N, Wessel, J, Selvaraj, MSunitha, Li, RH, Sun, X, Turner, AW, Stilp, AM, Khan, A, Newman, AB, Rasheed, A, Freedman, BI, Kral, BG, McHugh, CP, Hodonsky, C, Saleheen, D, Herrington, DM, Jacobs, DR, Nickerson, DA, Boerwinkle, E, Wang, FFei, Heiss, G, Jun, G, Kinney, GL, Sigurslid, HH, Doddapaneni, H, Hall, IM, Bensenor, IM, Broome, J, Crapo, JD, Wilson, JG, Smith, JA, Blangero, J, Vargas, JD, Mosquera, JVerdezoto, Smith, JD, Viaud-Martinez, KA, Ryan, KA, Young, KA, Taylor, KD, Lange, LA, Emery, LS, Bittencourt, MS, Budoff, MJ, Montasser, ME, Yu, M, Mahaney, MC, Mahamdeh, MS, Fornage, M, Franceschini, N, Lotufo, PA, Natarajan, P, Wong, Q, Mathias, RA, Gibbs, RA, Do, R, Mehran, R, Tracy, RP, Kim, RW, Nelson, SC, Damrauer, SM, Kardia, SLR, Rich, SS, Fuster, V, Napolioni, V, Zhao, W, Tian, W, Yin, X, Min, Y-I, Manning, AK, Peloso, G, Kelly, TN, O'Donnell, CJ, Morrison, AC, Curran, JE, Zapol, WM, Bowden, DW, Becker, LC, Correa, A, Mitchell, BD, Psaty, BM, Carr, JJeffrey, Pereira, AC, Assimes, TL, Stitziel, NO, Hokanson, JE, Laurie, CA, Rotter, JI, Vasan, RS, Post, WS, Peyser, PA, Miller, CL, Malhotra, R |
Journal | Nat Cardiovasc Res |
Volume | 2 |
Issue | 12 |
Pagination | 1159-1172 |
Date Published | 2023 Dec |
ISSN | 2731-0590 |
Abstract | Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC ( and ), with evidence of significant associations in replication analyses for both novel loci. Functional assays of and in human vascular smooth muscle cells (VSMCs) demonstrate that is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying or osteogenic phenotype. Furthermore, we show that the association of variants near with reduced CAC is likely explained by reduced expression with the G allele of enhancer variant rs5982944. Our study highlights ARSE as an important contributor to atherosclerotic vascular calcification, and a potential drug target for vascular calcific disease. |
DOI | 10.1038/s44161-023-00375-y |
Alternate Journal | Nat Cardiovasc Res |
PubMed ID | 38817323 |
PubMed Central ID | PMC11138106 |
Grant List | R01 HL120393 / HL / NHLBI NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States R01 HL162928 / HL / NHLBI NIH HHS / United States R01 HL146860 / HL / NHLBI NIH HHS / United States R01 HL164577 / HL / NHLBI NIH HHS / United States R01 HL148239 / HL / NHLBI NIH HHS / United States U01 HL137162 / HL / NHLBI NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States R01 HL142809 / HL / NHLBI NIH HHS / United States R01 HL159514 / HL / NHLBI NIH HHS / United States R01 HL142711 / HL / NHLBI NIH HHS / United States |