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Rare variants in fox-1 homolog A (RBFOX1) are associated with lower blood pressure.

Rare variants in fox-1 homolog A (RBFOX1) are associated with lower blood pressure.

Authors :
He KY
Wang H
Cade BE
Nandakumar P
Giri A
Ware EB
Haessler J
Liang J
Smith JA
Franceschini N
Le TH
Kooperberg C
Edwards TL
Kardia SL
Lin X
Chakravarti A
Redline S
Zhu X
Source :
PLoS genetics [PLoS Genet] 2017 Mar 27; Vol. 13 (3), pp. e1006678. Date of Electronic Publication: 2017 Mar 27 (Print Publication: 2017).
Publication Year :
2017

Abstract

Many large genome-wide association studies (GWAS) have identified common blood pressure (BP) variants. However, most of the identified BP variants do not overlap with the linkage evidence observed from family studies. We thus hypothesize that multiple rare variants contribute to the observed linkage evidence. We performed linkage analysis using 517 individuals in 130 European families from the Cleveland Family Study (CFS) who have been genotyped on the Illumina OmniExpress Exome array. The largest linkage peak was observed on chromosome 16p13 (MLOD = 2.81) for systolic blood pressure (SBP). Follow-up conditional linkage and association analyses in the linkage region identified multiple rare, coding variants in RBFOX1 associated with reduced SBP. In a 17-member CFS family, carriers of the missense variant rs149974858 are normotensive despite being obese (average BMI = 60 kg/m2). Gene-based association test of rare variants using SKAT-O showed significant association with SBP (p-value = 0.00403) and DBP (p-value = 0.0258) in the CFS participants and the association was replicated in large independent replication studies (N = 57,234, p-value = 0.013 for SBP, 0.0023 for PP). RBFOX1 is expressed in brain tissues, the atrial appendage and left ventricle in the heart, and in skeletal muscle tissues, organs/tissues which are potentially related to blood pressure. Our study showed that associations of rare variants could be efficiently detected using family information.

Details

Language :
English
ISSN :
1553-7404
Volume :
13
Issue :
3
Database :
MEDLINE
Journal :
PLoS genetics
Publication Type :
Academic Journal
Accession number :
28346479
Full Text :
https://doi.org/10.1371/journal.pgen.1006678