PuSH - Publikationsserver des Helmholtz Zentrums München

Portilla-Fernandez, E.* ; Klarin, D.* ; Hwang, S.J.* ; Biggs, M.L.* ; Bis, J.C.* ; Weiss, S.* ; Rospleszcz, S. ; Natarajan, P.* ; Hoffmann, U.* ; Rogers, I.S.* ; Truong, Q.A.* ; Völker, U.* ; Dörr, M.* ; Bülow, R.* ; Criqui, M.H.* ; Allison, M.* ; Ganesh, S.K.* ; Yao, J.* ; Waldenberger, M. ; Bamberg, F.* ; Rice, K.M.* ; Essers, J.* ; Kapteijn, D.M.C.* ; van der Laan, S.W.* ; de Knegt, R.J.* ; Ghanbari, M.* ; Felix, J.F.* ; Ikram, M.A.* ; Kavousi, M.* ; Uitterlinden, A.G.* ; Roks, A.J.M.* ; Danser, A.H.J.* ; Tsao, P.S.* ; Damrauer, S.M.* ; Guo, X.* ; Rotter, J.I.* ; Psaty, B.M.* ; Kathiresan, S.* ; Völzke, H.* ; Peters, A. ; Johnson, C.* ; Strauch, K. ; Meitinger, T. ; O'Donnell, C.J.* ; Dehghan, A.*

Genetic and clinical determinants of abdominal aortic diameter: Genome-wide association studies, exome array data and Mendelian randomization study.

Hum. Mol. Genet. 31, 3566-3579 (2022)
Verlagsversion Postprint DOI PMC
Open Access Gold (Paid Option)
Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of Abdominal Aortic Aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in ten cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects (PBIO) as replication. Maximum anterior-posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In GWAS on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = -0.02, SE = 0.004, p-value = 2.10 × 10-8). The association replicated in the PBIO1 cohort (p-value = 8.19 × 10-4). In exome-array single-variant analysis (p-value threshold = 9 × 10-7), the lowest p-value was found for rs239259 located in SLC22A20 (beta = 0.007, p-value =1.2 × 10-5). In the gene-based analysis (p-value threshold = 1.85 × 10-6), PCSK5 showed an association with AAD (p-value = 8.03 × 10-7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = -0.003, p-value = 0.02), triglycerides (beta = -0.16, p-value = 0.008) and height (beta = 0.03, p-value<0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter KORA-MRT, Herz-Kreislauf, Genetik
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 31, Heft: 20, Seiten: 3566-3579 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Förderungen NHLBI NIH HHS