TY - JOUR T1 - <em>DCAF4</em>, a novel gene associated with leucocyte telomere length JF - Journal of Medical Genetics JO - J Med Genet SP - 157 LP - 162 DO - 10.1136/jmedgenet-2014-102681 VL - 52 IS - 3 AU - Massimo Mangino AU - Lene Christiansen AU - Rivka Stone AU - Steven C Hunt AU - Kent Horvath AU - Dan T A Eisenberg AU - Masayuki Kimura AU - Inge Petersen AU - Jeremy D Kark AU - Utz Herbig AU - Alex P Reiner AU - Athanase Benetos AU - Veryan Codd AU - Dale R Nyholt AU - Ronit Sinnreich AU - Kaare Christensen AU - Hisham Nassar AU - Shih-Jen Hwang AU - Daniel Levy AU - Veronique Bataille AU - Annette L Fitzpatrick AU - Wei Chen AU - Gerald S Berenson AU - Nilesh J Samani AU - Nicholas G Martin AU - Sarah Tishkoff AU - Nicholas J Schork AU - Kirsten Ohm Kyvik AU - Christine Dalgård AU - Timothy D Spector AU - Abraham Aviv Y1 - 2015/03/01 UR - http://jmg.bmj.com/content/52/3/157.abstract N2 - Background Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR).Results Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10−10) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10−3 and 2×10−3, respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p&lt;0.05, &lt;0.01, &lt;0.005, &lt;0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10−169 to 3.42×10−24.Conclusions We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population. ER -