Common variants near TERC are associated with mean telomere length

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.

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 *