Journal article
Exome sequencing analysis identifies rare variants in ATM and RPL8 that are associated with shorter telomere length
- Abstract:
- Telomeres are important for maintaining genomic stability. Telomere length has been associated with aging, disease, and mortality and is highly heritable (∼82%). In this study, we aimed to identify rare genetic variants associated with telomere length using whole-exome sequence data. We studied 1,303 participants of the Erasmus Rucphen Family (ERF) study, 1,259 of the Rotterdam Study (RS), and 674 of the British Heart Foundation Family Heart Study (BHF-FHS). We conducted two analyses, first we analyzed the family-based ERF study and used the RS and BHF-FHS for replication. Second, we combined the summary data of the three studies in a meta-analysis. Telomere length was measured by quantitative polymerase chain reaction in blood. We identified nine rare variants significantly associated with telomere length (p-value < 1.42 × 10–7, minor allele frequency of 0.2–0.5%) in the ERF study. Eight of these variants (in C11orf65, ACAT1, NPAT, ATM, KDELC2, and EXPH5) were located on chromosome 11q22.3 that contains ATM, a gene involved in telomere maintenance. Although we were unable to replicate the variants in the RS and BHF-FHS (p-value ≥ 0.21), segregation analysis showed that all variants segregate with shorter telomere length in a family. In the meta-analysis of all studies, a nominally significant association with LTL was observed with a rare variant in RPL8 (p-value = 1.48 × 10−6), which has previously been associated with age. Additionally, a novel rare variant in the known RTEL1 locus showed suggestive evidence for association (p-value = 1.18 × 10–4) with LTL. To conclude, we identified novel rare variants associated with telomere length. Larger samples size are needed to confirm these findings and to identify additional variants.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 2.1MB, Terms of use)
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- Publisher copy:
- 10.3389/fgene.2020.00337
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Genetics More from this journal
- Volume:
- 11
- Article number:
- 337
- Publication date:
- 2020-04-30
- Acceptance date:
- 2020-03-20
- DOI:
- EISSN:
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1664-8021
- Pmid:
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32425970
- Language:
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English
- Keywords:
- Pubs id:
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1106234
- Local pid:
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pubs:1106234
- Deposit date:
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2020-06-02
Terms of use
- Copyright holder:
- van der Spek, Warner, Broer, Nelson, Vojinovic, Ahmad, Arp, Brouwer, Denniff, van den Hout, van Rooij, Kraaij, van IJcken, Samani, Ikram, Uitterlinden, Codd, Amin and van Duijn.
- Copyright date:
- 2020
- Rights statement:
- Copyright © 2020 van der Spek, Warner, Broer, Nelson, Vojinovic, Ahmad, Arp, Brouwer, Denniff, van den Hout, van Rooij, Kraaij, van IJcken, Samani, Ikram, Uitterlinden, Codd, Amin and van Duijn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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