A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm

Gregory T. Jones, Matthew J. Bown, Solveig Gretarsdottir, Simon P.R. Romaine, Anna Helgadottir, Grace Yu, Gerard Tromp, Paul E. Norman, Cao Jin, Annette F. Baas, Jan D. Blankensteijn, Iftikhar J. Kullo, L. Victoria Phillips, Michael J.A. Williams, Ruth Topless, Tony R. Merriman, Thodor M. Vasudevan, David R. Lewis, Ross D. Blair, Andrew A. HillRobert D. Sayers, Janet T. Powell, Panagiotis Deloukas, Gudmar Thorleifsson, Stefan E. Matthiasson, Unnur Thorsteinsdottir, Jonathan Golledge, Robert A. Ariëns, Anne Johnson, Soroush Sohrabi, D. Julian Scott, David J. Carey, Robert Erdman, James R. Elmore, Helena Kuivaniemi, Nilesh J. Samani, Kari Stefansson, Andre M. van Rij

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Abdominal aortic aneurysm (AAA) is a common human disease with a high estimated heritability (0.7); however, only a small number of associated genetic loci have been reported to date. In contrast, over 100 loci have now been reproducibly associated with either blood lipid profile and/or coronary artery disease (CAD) (both risk factors for AAA) in large-scale meta-analyses. This study employed a staged design to investigate whether the loci for these two phenotypes are also associated with AAA. Validated CAD and dyslipidaemia loci underwent screening using the Otago AAA genome-wide association data set. Putative associations underwent staged secondary validation in 10 additional cohorts. A novel association between the SORT1 (1p13.3) locus and AAA was identified. The rs599839 G allele, which has been previously associated with both dyslipidaemia and CAD, reached genome-wide significance in 11 combined independent cohorts (meta-analysis with 7048 AAA cases and 75 976 controls: G allele OR 0.81, 95% CI 0.76-0.85, P 5 7.2 3 10214). Modelling for confounding interactions of concurrent dyslipidaemia, heart disease and other risk factors suggested that this marker is an independent predictor of AAA susceptibility. In conclusion, a genetic marker associated with cardiovascular risk factors, and in particular concurrent vascular disease, appeared to independently contribute to susceptibility for AAA. Given the potential genetic overlap between risk factor and disease phenotypes, the use of well-characterized case-control cohorts allowing for modelling of cardiovascular disease risk confounders will be an important component in the future discovery of genetic markers for conditions such as AAA.

Original languageEnglish (US)
Article numberddt141
Pages (from-to)2941-2947
Number of pages7
JournalHuman molecular genetics
Issue number14
StatePublished - Jul 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A sequence variant associated with sortilin-1 (SORT1) on 1p13.3 is independently associated with abdominal aortic aneurysm'. Together they form a unique fingerprint.

Cite this