Genome 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
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...
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doaj-21690a8658c94853b7425bfa2d7b1e852020-11-24T23:57:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212014-01-01410.3389/fgene.2013.0031068695Genome 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 StudyJoseph H Lee0Joseph H Lee1Rong eCheng2Lawrence S Honig3Lawrence S Honig4Mary eFeitosa5Candace eKammerer6Min Suk Kang7Nicole eSchupf8Nicole eSchupf9Jiuan eLin10Jason L Sanders11Harold T Bae12Todd eDruley13Thomas T Perls14Kaare eChristensen15Michael eProvince16Richard eMayeux17Richard eMayeux18Richard eMayeux19Columbia UniversityColumbia UniversityColumbia UniversityColumbia UniversityColumbia UniversityWashington University School of MedicineUniversity of Pittsburgh, PittsburghColumbia UniversityColumbia UniversityColumbia UniversityWashington University School of MedicineUniversity of Pittsburgh, PittsburghBoston University Medical CenterWashington University School of MedicineBoston University Medical CenterUniversity of Southern DenmarkWashington University School of MedicineColumbia UniversityColumbia UniversityColumbia UniversityLeukocyte 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 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 pempirical smaller than 0.05.http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00310/fullAginggenome wide association studyleukocyte telomere lengthfamilial longevityfamily-based studynovel genes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Joseph H Lee Joseph H Lee Rong eCheng Lawrence S Honig Lawrence S Honig Mary eFeitosa Candace eKammerer Min Suk Kang Nicole eSchupf Nicole eSchupf Jiuan eLin Jason L Sanders Harold T Bae Todd eDruley Thomas T Perls Kaare eChristensen Michael eProvince Richard eMayeux Richard eMayeux Richard eMayeux |
spellingShingle |
Joseph H Lee Joseph H Lee Rong eCheng Lawrence S Honig Lawrence S Honig Mary eFeitosa Candace eKammerer Min Suk Kang Nicole eSchupf Nicole eSchupf Jiuan eLin Jason L Sanders Harold T Bae Todd eDruley Thomas T Perls Kaare eChristensen Michael eProvince Richard eMayeux Richard eMayeux Richard eMayeux Genome 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 Frontiers in Genetics Aging genome wide association study leukocyte telomere length familial longevity family-based study novel genes |
author_facet |
Joseph H Lee Joseph H Lee Rong eCheng Lawrence S Honig Lawrence S Honig Mary eFeitosa Candace eKammerer Min Suk Kang Nicole eSchupf Nicole eSchupf Jiuan eLin Jason L Sanders Harold T Bae Todd eDruley Thomas T Perls Kaare eChristensen Michael eProvince Richard eMayeux Richard eMayeux Richard eMayeux |
author_sort |
Joseph H Lee |
title |
Genome 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 |
title_short |
Genome 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 |
title_full |
Genome 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 |
title_fullStr |
Genome 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 |
title_full_unstemmed |
Genome 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 |
title_sort |
genome 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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2014-01-01 |
description |
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 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 pempirical smaller than 0.05. |
topic |
Aging genome wide association study leukocyte telomere length familial longevity family-based study novel genes |
url |
http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00310/full |
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