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. 2024 May 27;7(1):646.
doi: 10.1038/s42003-024-06299-y.

Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors

Isa Amalie Olofsson  1   2   3 , Ragnar P Kristjansson  1 , Ida Callesen  1 , Olafur Davidsson  1 , Bendik Winsvold  4   5   6 , Henrik Hjalgrim  7 , Sisse R Ostrowski  8   9 , Christian Erikstrup  10   11 , Mie Topholm Bruun  12 , Ole Birger Pedersen  13 , Kristoffer S Burgdorf  8 , Karina Banasik  14 , Erik Sørensen  8 , Christina Mikkelsen  8 , Maria Didriksen  8 , Khoa Manh Dinh  10 , Susan Mikkelsen  10 ; International Headache Genetic Consortium; DBDS Genomic Consortium; Søren Brunak  14 , Henrik Ullum  7 , Mona Ameri Chalmer  1 , Jes Olesen  1 , Lisette J A Kogelman  1   2 , Thomas Folkmann Hansen  15   16   17
Collaborators, Affiliations

Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors

Isa Amalie Olofsson et al. Commun Biol. .

Abstract

Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known. To assess genetic variants associated with complete freedom from headache, we performed a genome-wide association study of individuals who have never experienced a headache. We included 63,992 individuals (2,998 individuals with complete freedom from headache and 60,994 controls) from the Danish Blood Donor Study Genomic Cohort. Participants were included in two rounds, from 2015 to 2018 and in 2020. We discovered a genome-wide significant association, with the lead variant rs7904615[G] in ADARB2 (EAF = 27%, OR = 1.20 [1.13-1.27], p = 3.92 × 10-9). The genomic locus was replicated in a non-overlapping cohort of 13,032 individuals (539 individuals with complete freedom from headache and 12,493 controls) from the Danish Blood Donor Study Genomic Cohort (p < 0.05, two-sided). Participants for the replication were included from 2015 to 2020. In conclusion, we show that complete freedom from headache has a genetic component, and we suggest that ADARB2 is involved in complete freedom from headache. The genomic locus was specific for complete freedom from headache and was not associated with any primary headache disorders.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The significant loci in ADARB2 associated with complete freedom from headache (CFH).
Top panel: Manhattan plot of the GWAS of CFH. The red horizontal line denotes genome-wide significance (p = 5 × 10−8) and the blue horizontal line denotes suggestive association (p = 5 × 10−5). Mid panel: Regional locus zoom of the genome-wide significant risk locus, NCBI Build19. Each dot is colored by r2 of linkage disequilibrium (LD) with purple-colored lead SNP. 2,998 cases and 60,994 controls were analyzed. Bottom panel: Regional plot of ADARB2 and nearby genes, NCBI Build19.
See this image and copyright information in PMC

References

    1. Feigin VL, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:459–480. doi: 10.1016/S1474-4422(18)30499-X. - DOI - PMC - PubMed
    1. Steiner TJ, Stovner LJ, Jensen R, Uluduz D, Katsarava Z. Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J. Headache Pain. 2020;21:1–4. doi: 10.1186/s10194-020-01208-0. - DOI - PMC - PubMed
    1. Stovner LJ, Zwart J-A, Hagen K, Terwindt GM, Pascual J. Epidemiology of headache in Europe. Eur. J. Neurol. 2006;13:333–345. doi: 10.1111/j.1468-1331.2006.01184.x. - DOI - PubMed
    1. Rasmussen BK, Jensen R, Schroll M, Olesen J. Epidemiology of headache in a general population-A prevalence study. J. Clin. Epidemiol. 1991;44:1147–1157. doi: 10.1016/0895-4356(91)90147-2. - DOI - PubMed
    1. Olofsson IA, et al. Prevalence and socio-demographic characteristics of persons who have never had a headache among healthy voluntary blood donors – a population-based study. Cephalalgia. 2020;40:1055–1062. doi: 10.1177/0333102420920653. - DOI - PubMed

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