Research Repository

Functional Analysis of the Coronary Heart Disease Risk Locus on Chromosome 21q22

Beaney, KE and Smith, AJP and Folkersen, L and Palmen, J and Wannamethee, SG and Jefferis, BJ and Whincup, P and Gaunt, TR and Casas, JP and Ben-Shlomo, Y and Price, JF and Kumari, M and Wong, A and Ong, K and Hardy, R and Kuh, D and Wareham, N and Kivimaki, M and Eriksson, P and Humphries, SE (2017) 'Functional Analysis of the Coronary Heart Disease Risk Locus on Chromosome 21q22.' Disease Markers, 2017. ISSN 0278-0240

[img]
Preview
Text
1096916.pdf - Published Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

© 2017 Katherine E. Beaney et al. Background. The coronary heart disease (CHD) risk locus on 21q22 (lead SNP rs9982601) lies within a "gene desert." The aim of this study was to assess if this locus is associated with CHD risk factors and to identify the functional variant(s) and gene(s) involved. Methods. A phenome scan was performed with UCLEB Consortium data. Allele-specific protein binding was studied using electrophoretic mobility shift assays. Dual-reporter luciferase assays were used to assess the impact of genetic variation on expression. Expression quantitative trait analysis was performed with Advanced Study of Aortic Pathology (ASAP) and Genotype-Tissue Expression (GTEx) consortium data. Results. A suggestive association between QT interval and the locus was observed (rs9982601 p=0.04). One variant at the locus, rs28451064, showed allele-specific protein binding and its minor allele showed 12% higher luciferase expression (p = 4.82 × 10-3) compared to the common allele. The minor allele of rs9982601 was associated with higher expression of the closest upstream genes (SLC5A3 1.30-fold increase p = 3.98 × 10-5; MRPS6 1.15-fold increase p = 9.60 × 10-4) in aortic intima media in ASAP. Both rs9982601 and rs28451064 showed a suggestive association with MRPS6 expression in relevant tissues in the GTEx data. Conclusions. A candidate functional variant, rs28451064, was identified. Future work should focus on identifying the pathway(s) involved.

Item Type: Article
Subjects: H Social Sciences > H Social Sciences (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Social Sciences > Institute for Social and Economic Research
Depositing User: Jim Jamieson
Date Deposited: 26 May 2017 09:35
Last Modified: 11 Jun 2019 20:15
URI: http://repository.essex.ac.uk/id/eprint/19725

Actions (login required)

View Item View Item