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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...

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Autores principales: Stuart, Shani, Benton, Miles C., Eccles, David A., Sutherland, Heidi G., Haupt, Larisa M., Lea, Rodney A., Griffiths, Lyn R.
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
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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.
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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
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