Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
Jones, Gregory T. (författare)
Univ Otago, Dept Surg, Dunedin 9054, New Zealand.
Tromp, Gerard (författare)
Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.;Univ Stellenbosch, Dept Biomed Sci, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa.;deCODE Amgen, Reykjavik, Iceland.
Kuivaniemi, Helena (författare)
Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.;Univ Stellenbosch, Dept Biomed Sci, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa.
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Clin Gene Networks AB, Stockholm, Sweden.
Schadt, Eric E. (författare)
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
Bjorkegren, Johan L. M. (författare)
Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.;Univ Tartu, Inst Biomed & Translat Med, Dept Physiol, Tartu, Estonia.;Clin Gene Networks AB, Stockholm, Sweden.
Lipovich, Leonard (författare)
Wayne State Univ, Dept Neurol, Detroit, MI USA.
Drolet, Anne M. (författare)
Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.
Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
Deloukas, Panos (författare)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England. Univ Cambridge, Dept Haematol, Cambridge, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia.
Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)