Stuart Shani, Benton Miles C, Eccles David A, Sutherland Heidi G, Haupt Larisa M, Lea Rodney A, Griffiths Lyn R
Genomics Research Centre Institute for Biomedical Health and Innovation School of Biomedical Sciences Queensland University of Technology Brisbane Queensland 4059 Australia.
Mol Genet Genomic Med. 2017 Jan 17;5(2):157-163. doi: 10.1002/mgg3.270. eCollection 2017 Mar.
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.
A gene-centric association analysis of NEMP genes was undertaken in the most related individuals ( = 315) within the genetically isolated Norfolk Island population. The discovery phase included genes with three or more SNP associations ( < 0.005), which were investigated further in a replication phase using an unrelated migraine case-control cohort (544 patients and 584 controls).
The discovery phase of the study implicated SNPs in 5 NEMP genes to be associated with migraine susceptibility ( < 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 ( = 0.00037) ( = 0.00035) and ( = 0.00081), which are involved in phosphorylation, fatty acid metabolism, and oxidative demethylation, respectively.
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.
偏头痛是一种常见的神经系统疾病，影响着很大一部分人群。诺福克岛人群是一个基因隔离群体，鉴于其遗传和环境异质性降低，是研究复杂疾病易感性相关基因变异的理想发现队列。鉴于大多数负责线粒体功能的蛋白质是由核基因编码的，本研究旨在探讨核编码线粒体蛋白（NEMP）基因与偏头痛易感性的关系。
在基因隔离的诺福克岛人群中，对最相关的个体（n = 315）进行了NEMP基因的以基因为中心的关联分析。发现阶段包括与三个或更多单核苷酸多态性（SNP）关联（P < 0.005）的基因，在复制阶段使用不相关的偏头痛病例对照队列（544例患者和584例对照）对其进行进一步研究。
研究的发现阶段表明，5个NEMP基因中的SNP与偏头痛易感性相关（P < 0.005）。复制分析验证了其中一些相关基因，三个NEMP基因中的SNP在复制队列中显示与偏头痛相关。这些基因分别是（P = 0.00037）、（P = 0.00035）和（P = 0.00081），它们分别参与磷酸化、脂肪酸代谢和氧化去甲基化。
我们在此提供证据表明，NEMP基因的变异与偏头痛易感性相关。本研究为线粒体功能与偏头痛易感性之间的联系提供了证据。
