In:
Disease Markers, Hindawi Limited, Vol. 2017 ( 2017), p. 1-10
Abstract:
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 ( r s 9982601 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.
Type of Medium:
Online Resource
ISSN:
0278-0240
,
1875-8630
DOI:
10.1155/2017/1096916
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2017
detail.hit.zdb_id:
2033253-1
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