Weihong Tang1, Athanasios Saratzis2, Jack Pattee3, Jacqueline Smith4, Nathan Pankratz5, Olivia C Leavy6, Weihua Guan3, Frank Dudbridge7, James S Pankow8, George D Kitas9, Pamela L Lutsey8, Matthew J Bown10. 1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. Electronic address: tang0097@umn.edu. 2. Department of Cardiovascular Sciences and National Institute of Health Research (NIHR), Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. 3. Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA. 4. Dudley Group of Hospitals NHS Trust, Dudley, UK. 5. Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, MN, USA. 6. Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK; Department of Health Sciences, University of Leicester, Leicester, UK. 7. Department of Health Sciences, University of Leicester, Leicester, UK. 8. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. 9. College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK. 10. Department of Cardiovascular Sciences and National Institute of Health Research (NIHR), Leicester Biomedical Research Centre, University of Leicester, Leicester, UK. Electronic address: mjb42@leicester.ac.uk.
Abstract
OBJECTIVE: A recently published genome wide association study of abdominal aortic aneurysms (AAA), based on pooled case control data of European ancestry, identified four new loci for AAA: SMYD2 (top single nucleotide polymorphism [SNP] rs1795061), LINC00540 (rs9316871), PCIF1/MMP9/ZNF335 (rs3827066), and ERG (rs2836411). Of the four, rs1795061 and rs2836411 showed significant heterogeneity across studies and the p value for rs9316871 did not reach the genome wide significance threshold until discovery and replication data were pooled together in that study. The objective of this study was to replicate these newly identified genetic associations for AAA in a US based prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, and a Greece based case control study. METHODS: ARIC identified 408 clinically diagnosed AAAs among 8 962 individuals of European ancestry during a median of 22 years of follow up. The Greek case control study included 341 AAAs of European ancestry recruited in a tertiary referral centre and 292 geographically and ethnically matched controls recruited from the same institution. A Cox proportional hazards model was used to analyse the ARIC data and logistic regression to analyse the Greek data. RESULTS: In ARIC, rs9316871 and rs3827066 were significantly associated with AAA risk (HR [p] was 0.77 [.004] and 1.22 [.03], respectively), rs2836411 was associated at borderline significance (1.13 [.08]), whereas rs1795061 was not associated (p = .55). In the Greek case control study, rs1795061 and rs2836411 were significantly associated with AAA (OR [p] was 1.66 [< .001] and 1.29 [.04], respectively), whereas rs9316871 was not (p = .81). Genotyping of rs3827066 did not succeed. In the meta-analysis of the two studies, the association for rs9316871and rs2836411 was statistically significant and consistent between the two studies: p = .02 and .007, respectively. CONCLUSIONS: Associations between rs9316871and rs2836411 and AAA risk were replicated in the meta-analysis of the two independent cohorts, providing further support for the importance of these loci in the aetiology of AAA.
OBJECTIVE: A recently published genome wide association study of abdominal aortic aneurysms (AAA), based on pooled case control data of European ancestry, identified four new loci for AAA: SMYD2 (top single nucleotide polymorphism [SNP] rs1795061), LINC00540 (rs9316871), PCIF1/MMP9/ZNF335 (rs3827066), and ERG (rs2836411). Of the four, rs1795061 and rs2836411 showed significant heterogeneity across studies and the p value for rs9316871 did not reach the genome wide significance threshold until discovery and replication data were pooled together in that study. The objective of this study was to replicate these newly identified genetic associations for AAA in a US based prospective cohort study, the Atherosclerosis Risk in Communities (ARIC) Study, and a Greece based case control study. METHODS: ARIC identified 408 clinically diagnosed AAAs among 8 962 individuals of European ancestry during a median of 22 years of follow up. The Greek case control study included 341 AAAs of European ancestry recruited in a tertiary referral centre and 292 geographically and ethnically matched controls recruited from the same institution. A Cox proportional hazards model was used to analyse the ARIC data and logistic regression to analyse the Greek data. RESULTS: In ARIC, rs9316871 and rs3827066 were significantly associated with AAA risk (HR [p] was 0.77 [.004] and 1.22 [.03], respectively), rs2836411 was associated at borderline significance (1.13 [.08]), whereas rs1795061 was not associated (p = .55). In the Greek case control study, rs1795061 and rs2836411 were significantly associated with AAA (OR [p] was 1.66 [< .001] and 1.29 [.04], respectively), whereas rs9316871 was not (p = .81). Genotyping of rs3827066 did not succeed. In the meta-analysis of the two studies, the association for rs9316871and rs2836411 was statistically significant and consistent between the two studies: p = .02 and .007, respectively. CONCLUSIONS: Associations between rs9316871and rs2836411 and AAA risk were replicated in the meta-analysis of the two independent cohorts, providing further support for the importance of these loci in the aetiology of AAA.
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