Journal article
Whole-genome linkage scan combined with exome sequencing identifies novel candidate genes for carotid intima-media thickness
- Abstract:
- Carotid intima-media thickness (cIMT) is an established heritable marker for subclinical atherosclerosis. In this study, we aim to identify rare variants with large effects driving differences in cIMT by performing genome-wide linkage analysis of individuals in the extremes of cIMT trait distribution (>90th percentile) in a large family-based study from a genetically isolated population in the Netherlands. Linked regions were subsequently explored by fine-mapping using exome sequencing. We observed significant evidence of linkage on chromosomes 2p16.3 [rs1017418, heterogeneity LOD (HLOD) = 3.35], 19q13.43 (rs3499, HLOD = 9.09), 20p13 (rs1434789, HLOD = 4.10), and 21q22.12 (rs2834949, HLOD = 3.59). Fine-mapping using exome sequencing data identified a non-coding variant (rs62165235) in PNPT1 gene under the linkage peak at chromosome 2 that is likely to have a regulatory function. The variant was associated with quantitative cIMT in the family-based study population (effect = 0.27, p-value = 0.013). Furthermore, we identified several genes under the linkage peak at chromosome 21 highly expressed in tissues relevant for atherosclerosis. To conclude, our linkage analysis identified four genomic regions significantly linked to cIMT. Further analyses are needed to demonstrate involvement of identified candidate genes in development of atherosclerosis.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 1.6MB, Terms of use)
-
- Publisher copy:
- 10.3389/fgene.2018.00420
Authors
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Genetics More from this journal
- Volume:
- 9
- Issue:
- OCT
- Pages:
- 420
- Publication date:
- 2018-10-09
- Acceptance date:
- 2018-09-10
- DOI:
- EISSN:
-
1664-8021
- Pmid:
-
30356672
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:929717
- UUID:
-
uuid:086db45c-e879-4451-a876-e7961097dd12
- Local pid:
-
pubs:929717
- Source identifiers:
-
929717
- Deposit date:
-
2018-11-21
- ARK identifier:
Terms of use
- Copyright holder:
- Vojinovic et al
- Copyright date:
- 2018
- Notes:
- Copyright © 2018 Vojinovic, Kavousi, Ghanbari, Brouwer, van Rooij, van den Hout, Kraaij, van Ijcken, Uitterlinden, van Duijn and Amin. 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)
If you are the owner of this record, you can report an update to it here: Report update to this record