Sigrid Børte1,2,3, John-Anker Zwart1,2,3,4, Anne Heidi Skogholt3,5, Maiken Elvestad Gabrielsen3, Laurent F Thomas3,5, Lars G Fritsche6,7, Ida Surakka8, Jonas B Nielsen8, Wei Zhou9, Brooke N Wolford9, Magnus D Vigeland2,10, Knut Hagen11,12, Espen Saxhaug Kristoffersen1,13,14, Dale R Nyholt15, Daniel I Chasman16,17, Ben M Brumpton3, Cristen J Willer8,9,18, Bendik S Winsvold1,3,4. 1. Research and Communication Unit for Musculoskeletal Health, Division of Clinical Neuroscience, Oslo University Hospital, Ullevaal, Oslo, Norway. 2. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 3. K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. 4. Department of Neurology, Oslo University Hospital, Oslo, Norway. 5. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 6. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. 7. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA. 8. Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, Ann Arbor, MI, USA. 9. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. 10. Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. 11. Department of Neuromedicine and Movement Science, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 12. Norwegian Advisory Unit on Headache, Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, Trondheim, Norway. 13. Department of Neurology, Akershus University Hospital, Lorenskog, Norway. 14. Department of General Practice, Institute of Health and Society, University of Oslo, Oslo, Norway. 15. School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. 16. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, USA. 17. Harvard Medical School, Boston, MA, USA. 18. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
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.
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.
Authors: Lubna Al Asoom; Johra Khan; Ahmad Al Sunni; Nazish Rafique; Rabia Latif; Majed Alabdali; Sayed AbdulAzeez; J Francis Borgio Journal: Int J Gen Med Date: 2022-07-21