TY - JOUR
T1 - Genome-wide association study reveals a locus in ADARB2 for complete freedom from headache in Danish Blood Donors
AU - International Headache Genetic Consortium
AU - Olofsson, Isa Amalie
AU - Kristjansson, Ragnar P
AU - Callesen, Ida
AU - Davidsson, Olafur
AU - Winsvold, Bendik
AU - Hjalgrim, Henrik
AU - Ostrowski, Sisse R
AU - Erikstrup, Christian
AU - Bruun, Mie Topholm
AU - Pedersen, Ole Birger
AU - Burgdorf, Kristoffer S
AU - Banasik, Karina
AU - Sørensen, Erik
AU - Mikkelsen, Christina
AU - Didriksen, Maria
AU - Dinh, Khoa Manh
AU - Mikkelsen, Susan
AU - Brunak, Søren
AU - Ullum, Henrik
AU - Chalmer, Mona Ameri
AU - Olesen, Jes
AU - Kogelman, Lisette J A
AU - Hansen, Thomas Folkmann
N1 - © 2024. The Author(s).
PY - 2024/5/27
Y1 - 2024/5/27
N2 - 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.
AB - 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.
KW - Adult
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Blood Donors
KW - Cohort Studies
KW - Denmark/epidemiology
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Headache/genetics
KW - Polymorphism, Single Nucleotide
KW - RNA-Binding Proteins/genetics
U2 - 10.1038/s42003-024-06299-y
DO - 10.1038/s42003-024-06299-y
M3 - Article
C2 - 38802570
SN - 2399-3642
VL - 7
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 646
ER -