Cargando…
Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility
BACKGROUND: Migraine is a common neurological disorder which affects a large proportion of the population. The Norfolk Island population is a genetically isolated population and is an ideal discovery cohort for genetic variants involved in complex disease susceptibility given the reduced genetic and...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370233/ https://www.ncbi.nlm.nih.gov/pubmed/28361102 http://dx.doi.org/10.1002/mgg3.270 |
_version_ | 1782518201823789056 |
---|---|
author | Stuart, Shani Benton, Miles C. Eccles, David A. Sutherland, Heidi G. Haupt, Larisa M. Lea, Rodney A. Griffiths, Lyn R. |
author_facet | Stuart, Shani Benton, Miles C. Eccles, David A. Sutherland, Heidi G. Haupt, Larisa M. Lea, Rodney A. Griffiths, Lyn R. |
author_sort | Stuart, Shani |
collection | PubMed |
description | BACKGROUND: Migraine is a common neurological disorder which affects a large proportion of the population. The Norfolk Island population is a genetically isolated population and is an ideal discovery cohort for genetic variants involved in complex disease susceptibility given the reduced genetic and environmental heterogeneity. Given that the majority of proteins responsible for mitochondrial function are nuclear encoded, this study aimed to investigate the role of Nuclear Encoded Mitochondrial Protein (NEMP) genes in relation to migraine susceptibility. METHODS: A gene‐centric association analysis of NEMP genes was undertaken in the most related individuals (n = 315) within the genetically isolated Norfolk Island population. The discovery phase included genes with three or more SNP associations (P < 0.005), which were investigated further in a replication phase using an unrelated migraine case–control cohort (544 patients and 584 controls). RESULTS: The discovery phase of the study implicated SNPs in 5 NEMP genes to be associated with migraine susceptibility (P < 0.005). Replication analysis validated some of these implicated genes with SNPs in three NEMP genes shown to be associated with migraine in the replication cohort. These were CSNK1G3 (P = 0.00037), ELOVL6 (P = 0.00035) and SARDH (P = 0.00081), which are involved in phosphorylation, fatty acid metabolism, and oxidative demethylation, respectively. CONCLUSION: Here we provide evidence that variation in NEMP genes is associated with migraine susceptibility. This study provides evidence for a link between mitochondrial function and migraine susceptibility. |
format | Online Article Text |
id | pubmed-5370233 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53702332017-03-30 Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility Stuart, Shani Benton, Miles C. Eccles, David A. Sutherland, Heidi G. Haupt, Larisa M. Lea, Rodney A. Griffiths, Lyn R. Mol Genet Genomic Med Original Articles BACKGROUND: Migraine is a common neurological disorder which affects a large proportion of the population. The Norfolk Island population is a genetically isolated population and is an ideal discovery cohort for genetic variants involved in complex disease susceptibility given the reduced genetic and environmental heterogeneity. Given that the majority of proteins responsible for mitochondrial function are nuclear encoded, this study aimed to investigate the role of Nuclear Encoded Mitochondrial Protein (NEMP) genes in relation to migraine susceptibility. METHODS: A gene‐centric association analysis of NEMP genes was undertaken in the most related individuals (n = 315) within the genetically isolated Norfolk Island population. The discovery phase included genes with three or more SNP associations (P < 0.005), which were investigated further in a replication phase using an unrelated migraine case–control cohort (544 patients and 584 controls). RESULTS: The discovery phase of the study implicated SNPs in 5 NEMP genes to be associated with migraine susceptibility (P < 0.005). Replication analysis validated some of these implicated genes with SNPs in three NEMP genes shown to be associated with migraine in the replication cohort. These were CSNK1G3 (P = 0.00037), ELOVL6 (P = 0.00035) and SARDH (P = 0.00081), which are involved in phosphorylation, fatty acid metabolism, and oxidative demethylation, respectively. CONCLUSION: Here we provide evidence that variation in NEMP genes is associated with migraine susceptibility. This study provides evidence for a link between mitochondrial function and migraine susceptibility. John Wiley and Sons Inc. 2017-01-17 /pmc/articles/PMC5370233/ /pubmed/28361102 http://dx.doi.org/10.1002/mgg3.270 Text en © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Stuart, Shani Benton, Miles C. Eccles, David A. Sutherland, Heidi G. Haupt, Larisa M. Lea, Rodney A. Griffiths, Lyn R. Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
title | Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
title_full | Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
title_fullStr | Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
title_full_unstemmed | Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
title_short | Gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
title_sort | gene‐centric analysis implicates nuclear encoded mitochondrial protein gene variants in migraine susceptibility |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370233/ https://www.ncbi.nlm.nih.gov/pubmed/28361102 http://dx.doi.org/10.1002/mgg3.270 |
work_keys_str_mv | AT stuartshani genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility AT bentonmilesc genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility AT ecclesdavida genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility AT sutherlandheidig genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility AT hauptlarisam genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility AT learodneya genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility AT griffithslynr genecentricanalysisimplicatesnuclearencodedmitochondrialproteingenevariantsinmigrainesusceptibility |