Common variants near TERC are associated with mean telomere length

Veryan Codd, Massimo Mangino, Pim van der Harst, Peter S Braund, Michael Kaiser, Alan J Beveridge, Suzanne Rafelt, Jasbir Moore, Chris Nelson, Nicole Soranzo, Guangju Zhai, Ana M Valdes, Hannah Blackburn, Irene Mateo Leach, Rudolf A de Boer, Masayuki Kimura, Abraham Aviv, Wellcome Trust Case Control Consortium, Alison H Goodall, Willem Ouwehand, Dirk J van Veldhuisen, Wiek H van Gilst, Gerjan Navis, Paul R Burton, Martin D Tobin, Alistair S Hall, John R Thompson, Tim Spector, Nilesh J Samani, Veryan Codd, Massimo Mangino, Pim van der Harst, Peter S Braund, Michael Kaiser, Alan J Beveridge, Suzanne Rafelt, Jasbir Moore, Chris Nelson, Nicole Soranzo, Guangju Zhai, Ana M Valdes, Hannah Blackburn, Irene Mateo Leach, Rudolf A de Boer, Masayuki Kimura, Abraham Aviv, Wellcome Trust Case Control Consortium, Alison H Goodall, Willem Ouwehand, Dirk J van Veldhuisen, Wiek H van Gilst, Gerjan Navis, Paul R Burton, Martin D Tobin, Alistair S Hall, John R Thompson, Tim Spector, Nilesh J Samani

Abstract

We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 x 10(-14)) at a locus that includes TERC, which encodes the telomerase RNA component. Each copy of the minor allele of rs12696304 was associated with an approximately 75-base-pair reduction in mean telomere length, equivalent to approximately 3.6 years of age-related telomere-length attrition.

Figures

Figure 1
Figure 1
A map of the chromosome 3q26 region showing genetic association with mean leukocyte telomere length. Association of individual SNPs from the combined BHF-FHS and UKBS analysis is plotted as −log10P against chromosomal base pair position. Results of both genotyped and imputed SNPs are shown. rs12696304 is shown in blue and the LD relationship of the other markers (including rs16847897) to rs12696304 SNP is indicated by colour: red R2>0.8, orange R2>0.5, yellow R2>0.2, white R2<0.2. The location of known genes in the region ARPM1 (Actin-related protein M1), MYNN (myoneurin) and three members of the leucine-rich repeat containing (LRRC) superfamily (LRRC34, LRRC31 and LRRIQ4) are shown as well as the location of recombination hot spots (blue peaks). The position of the TERC coding sequence (451bp) is represented by *

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren