TitleGenome wide association and linkage analyses identified three loci-4q25, 17q23.2, and 10q11.21-associated with variation in leukocyte telomere length: the Long Life Family Study.
Publication TypeJournal Article
Year of Publication2013
AuthorsLee, JH, Cheng, R, Honig, LS, Feitosa, M, Kammerer, CM, Kang, MS, Schupf, N, Lin, SJ, Sanders, JL, Bae, H, Druley, T, Perls, T, Christensen, K, Province, M, Mayeux, R
JournalFront Genet
Date Published12/2013

Leukocyte telomere length is believed to measure cellular aging in humans, and short leukocyte telomere length is associated with increased risks of late onset diseases, including cardiovascular disease, dementia, etc. Many studies have shown that leukocyte telomere length is a heritable trait, and several candidate genes have been identified, including TERT, TERC, OBFC1, and CTC1. Unlike most studies that have focused on genetic causes of chronic diseases such as heart disease and diabetes in relation to leukocyte telomere length, the present study examined the genome to identify variants that may contribute to variation in leukocyte telomere length among families with exceptional longevity. From the genome wide association analysis in 4,289 LLFS participants, we identified a novel intergenic SNP rs7680468 located near PAPSS1 and DKK2 on 4q25 (p = 4.7E-8). From our linkage analysis, we identified two additional novel loci with HLOD scores exceeding three, including 4.77 for 17q23.2, and 4.36 for 10q11.21. These two loci harbor a number of novel candidate genes with SNPs, and our gene-wise association analysis identified multiple genes, including DCAF7, POLG2, CEP95, and SMURF2 at 17q23.2; and RASGEF1A, HNRNPF, ANF487, CSTF2T, and PRKG1 at 10q11.21. Among these genes, multiple SNPs were associated with leukocyte telomere length, but the strongest association was observed with one contiguous haplotype in CEP95 and SMURF2. We also show that three previously reported genes-TERC, MYNN, and OBFC1-were significantly associated with leukocyte telomere length at p empirical < 0.05.

Alternate JournalFront Genet
PubMed ID24478790
PubMed Central IDPMC3894567
Grant ListU01 AG023712 / AG / NIA NIH HHS / United States
U01 AG023744 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
P30 AG034424 / AG / NIA NIH HHS / United States
U01 AG023749 / AG / NIA NIH HHS / United States
U01 AG023755 / AG / NIA NIH HHS / United States
U01 AG023746 / AG / NIA NIH HHS / United States
R01 MH084995 / MH / NIMH NIH HHS / United States