PT - JOURNAL ARTICLE AU - Mangino, Massimo AU - Christiansen, Lene AU - Stone, Rivka AU - Hunt, Steven C AU - Horvath, Kent AU - Eisenberg, Dan T A AU - Kimura, Masayuki AU - Petersen, Inge AU - Kark, Jeremy D AU - Herbig, Utz AU - Reiner, Alex P AU - Benetos, Athanase AU - Codd, Veryan AU - Nyholt, Dale R AU - Sinnreich, Ronit AU - Christensen, Kaare AU - Nassar, Hisham AU - Hwang, Shih-Jen AU - Levy, Daniel AU - Bataille, Veronique AU - Fitzpatrick, Annette L AU - Chen, Wei AU - Berenson, Gerald S AU - Samani, Nilesh J AU - Martin, Nicholas G AU - Tishkoff, Sarah AU - Schork, Nicholas J AU - Kyvik, Kirsten Ohm AU - Dalgård, Christine AU - Spector, Timothy D AU - Aviv, Abraham TI - <em>DCAF4</em>, a novel gene associated with leucocyte telomere length AID - 10.1136/jmedgenet-2014-102681 DP - 2015 Mar 01 TA - Journal of Medical Genetics PG - 157--162 VI - 52 IP - 3 4099 - http://jmg.bmj.com/content/52/3/157.short 4100 - http://jmg.bmj.com/content/52/3/157.full SO - J Med Genet2015 Mar 01; 52 AB - 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.