Dataset Information

Mitochondrial genome-wide association study of migraine - the HUNT Study.

ABSTRACT: BACKGROUND:Variation in mitochondrial DNA (mtDNA) has been indicated in migraine pathogenesis, but genetic studies to date have focused on candidate variants, with sparse findings. We aimed to perform the first mitochondrial genome-wide association study of migraine, examining both single variants and mitochondrial haplogroups. METHODS:In total, 71,860 participants from the population-based Nord-Trøndelag Health Study were genotyped. We excluded samples not passing quality control for nuclear genotypes, in addition to samples with low call rate and closely maternally related. We analysed 775 mitochondrial DNA variants in 4021 migraine cases and 14,288 headache-free controls, using logistic regression. In addition, we analysed 3831 cases and 13,584 controls who could be reliably assigned to a mitochondrial haplogroup. Lastly, we attempted to replicate previously reported mitochondrial DNA candidate variants. RESULTS:Neither of the mitochondrial variants or haplogroups were associated with migraine. In addition, none of the previously reported mtDNA candidate variants replicated in our data. CONCLUSIONS:Our findings do not support a major role of mitochondrial genetic variation in migraine pathophysiology, but a larger sample is needed to detect rare variants and future studies should also examine heteroplasmic variation, epigenetic changes and copy-number variation.

SUBMITTER: Borte S

PROVIDER: S-EPMC7243449 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Mitochondrial genome-wide association study of migraine - the HUNT Study.

Børte Sigrid S Zwart John-Anker JA Skogholt Anne Heidi AH Gabrielsen Maiken Elvestad ME Thomas Laurent F LF Fritsche Lars G LG Surakka Ida I Nielsen Jonas B JB Zhou Wei W Wolford Brooke N BN Vigeland Magnus D MD Hagen Knut K Kristoffersen Espen Saxhaug ES Nyholt Dale R DR Chasman Daniel I DI Brumpton Ben M BM Willer Cristen J CJ Winsvold Bendik S BS

Cephalalgia : an international journal of headache 20200214 6

<h4>Background</h4>Variation in mitochondrial DNA (mtDNA) has been indicated in migraine pathogenesis, but genetic studies to date have focused on candidate variants, with sparse findings. We aimed to perform the first mitochondrial genome-wide association study of migraine, examining both single variants and mitochondrial haplogroups.<h4>Methods</h4>In total, 71,860 participants from the population-based Nord-Trøndelag Health Study were genotyped. We excluded samples not passing quality control ...[more]

PMID: 32056457

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Project description:Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR?=?6.37; 95% CI 3.15-12.90; p?=?2.7×10(-7)) and rs4975709 in IRX4 (OR?=?5.06; 95% CI 2.66-9.62; p?=?7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR?=?3.05; 95% CI 1.98-4.69; p?=?4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR?=?12.33; 95% CI 4.62-32.87; p?=?5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR?=?4.67; 95% CI 2.53-8.62; p?=?8.0×10(-7)).Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research.

Dataset Information

Mitochondrial genome-wide association study of migraine - the HUNT Study.

Publications

Mitochondrial genome-wide association study of migraine - the HUNT Study.

Similar Datasets

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