Standard
Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura. / Bjornsdottir, Gyda; Chalmer, Mona A.; Stefansdottir, Lilja; Skuladottir, Astros Th; Einarsson, Gudmundur; Andresdottir, Margret; Beyter, Doruk; Ferkingstad, Egil; Gretarsdottir, Solveig; Halldorsson, Bjarni V.; Halldorsson, Gisli H.; Helgadottir, Anna; Helgason, Hannes; Hjorleifsson Eldjarn, Grimur; Jonasdottir, Adalbjorg; Jonasdottir, Aslaug; Jonsdottir, Ingileif; Knowlton, Kirk U.; Nadauld, Lincoln D.; Lund, Sigrun H.; Magnusson, Olafur Th; Melsted, Pall; Moore, Kristjan H.S.; Oddsson, Asmundur; Olason, Pall I.; Sigurdsson, Asgeir; Banasik, Karina; Brunak, Søren; Didriksen, Maria; Kogelman, Lisette J.A.; Nielsen, Kaspar R.; Sørensen, Erik; Pedersen, Ole B.; Ullum, Henrik; Bay, Jakob; Burgdorf, Kristoffer; Dowsett, Joseph; Hjalgrim, Henrik; Jacobsen, Rikke L.; Louloudis, Ioannis; Lundgaard, Agnete; Mikkelsen, Christina; Nyegaard, Mette; Henriksen, Alexander P.; Werge, Thomas; Westergaard, David; Olesen, Jes; Ostrowski, Sisse R.; Hansen, Thomas F.; DBDS Genetic Consortium.
In:
Nature Genetics, Vol. 55, No. 11, 2023, p. 1843-1853.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Bjornsdottir, G, Chalmer, MA, Stefansdottir, L, Skuladottir, AT, Einarsson, G, Andresdottir, M, Beyter, D, Ferkingstad, E, Gretarsdottir, S, Halldorsson, BV, Halldorsson, GH, Helgadottir, A, Helgason, H, Hjorleifsson Eldjarn, G, Jonasdottir, A, Jonasdottir, A, Jonsdottir, I, Knowlton, KU, Nadauld, LD, Lund, SH, Magnusson, OT, Melsted, P, Moore, KHS, Oddsson, A, Olason, PI, Sigurdsson, A
, Banasik, K, Brunak, S, Didriksen, M, Kogelman, LJA, Nielsen, KR, Sørensen, E
, Pedersen, OB, Ullum, H, Bay, J
, Burgdorf, K, Dowsett, J
, Hjalgrim, H, Jacobsen, RL
, Louloudis, I, Lundgaard, A, Mikkelsen, C, Nyegaard, M, Henriksen, AP, Werge, T, Westergaard, D, Olesen, J, Ostrowski, SR, Hansen, TF & DBDS Genetic Consortium 2023, '
Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura',
Nature Genetics, vol. 55, no. 11, pp. 1843-1853.
https://doi.org/10.1038/s41588-023-01538-0APA
Bjornsdottir, G., Chalmer, M. A., Stefansdottir, L., Skuladottir, A. T., Einarsson, G., Andresdottir, M., Beyter, D., Ferkingstad, E., Gretarsdottir, S., Halldorsson, B. V., Halldorsson, G. H., Helgadottir, A., Helgason, H., Hjorleifsson Eldjarn, G., Jonasdottir, A., Jonasdottir, A., Jonsdottir, I., Knowlton, K. U., Nadauld, L. D., ... DBDS Genetic Consortium (2023).
Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura.
Nature Genetics,
55(11), 1843-1853.
https://doi.org/10.1038/s41588-023-01538-0Vancouver
Bjornsdottir G, Chalmer MA, Stefansdottir L, Skuladottir AT, Einarsson G, Andresdottir M et al.
Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura.
Nature Genetics. 2023;55(11):1843-1853.
https://doi.org/10.1038/s41588-023-01538-0Author
Bjornsdottir, Gyda ; Chalmer, Mona A. ; Stefansdottir, Lilja ; Skuladottir, Astros Th ; Einarsson, Gudmundur ; Andresdottir, Margret ; Beyter, Doruk ; Ferkingstad, Egil ; Gretarsdottir, Solveig ; Halldorsson, Bjarni V. ; Halldorsson, Gisli H. ; Helgadottir, Anna ; Helgason, Hannes ; Hjorleifsson Eldjarn, Grimur ; Jonasdottir, Adalbjorg ; Jonasdottir, Aslaug ; Jonsdottir, Ingileif ; Knowlton, Kirk U. ; Nadauld, Lincoln D. ; Lund, Sigrun H. ; Magnusson, Olafur Th ; Melsted, Pall ; Moore, Kristjan H.S. ; Oddsson, Asmundur ; Olason, Pall I. ; Sigurdsson, Asgeir ; Banasik, Karina ; Brunak, Søren ; Didriksen, Maria ; Kogelman, Lisette J.A. ; Nielsen, Kaspar R. ; Sørensen, Erik ; Pedersen, Ole B. ; Ullum, Henrik ; Bay, Jakob ; Burgdorf, Kristoffer ; Dowsett, Joseph ; Hjalgrim, Henrik ; Jacobsen, Rikke L. ; Louloudis, Ioannis ; Lundgaard, Agnete ; Mikkelsen, Christina ; Nyegaard, Mette ; Henriksen, Alexander P. ; Werge, Thomas ; Westergaard, David ; Olesen, Jes ; Ostrowski, Sisse R. ; Hansen, Thomas F. ; DBDS Genetic Consortium. / Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura. In: Nature Genetics. 2023 ; Vol. 55, No. 11. pp. 1843-1853.
Bibtex
@article{2951c4b08c4a44fb8d6615c4fba70b29,
title = "Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura",
abstract = "Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.",
author = "Gyda Bjornsdottir and Chalmer, {Mona A.} and Lilja Stefansdottir and Skuladottir, {Astros Th} and Gudmundur Einarsson and Margret Andresdottir and Doruk Beyter and Egil Ferkingstad and Solveig Gretarsdottir and Halldorsson, {Bjarni V.} and Halldorsson, {Gisli H.} and Anna Helgadottir and Hannes Helgason and {Hjorleifsson Eldjarn}, Grimur and Adalbjorg Jonasdottir and Aslaug Jonasdottir and Ingileif Jonsdottir and Knowlton, {Kirk U.} and Nadauld, {Lincoln D.} and Lund, {Sigrun H.} and Magnusson, {Olafur Th} and Pall Melsted and Moore, {Kristjan H.S.} and Asmundur Oddsson and Olason, {Pall I.} and Asgeir Sigurdsson and Karina Banasik and S{\o}ren Brunak and Maria Didriksen and Kogelman, {Lisette J.A.} and Nielsen, {Kaspar R.} and Erik S{\o}rensen and Pedersen, {Ole B.} and Henrik Ullum and Jakob Bay and Kristoffer Burgdorf and Joseph Dowsett and Henrik Hjalgrim and Jacobsen, {Rikke L.} and Ioannis Louloudis and Agnete Lundgaard and Christina Mikkelsen and Mette Nyegaard and Henriksen, {Alexander P.} and Thomas Werge and David Westergaard and Jes Olesen and Ostrowski, {Sisse R.} and Hansen, {Thomas F.} and {DBDS Genetic Consortium}",
note = "Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s41588-023-01538-0",
language = "English",
volume = "55",
pages = "1843--1853",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "11",
}
RIS
TY - JOUR
T1 - Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura
AU - Bjornsdottir, Gyda
AU - Chalmer, Mona A.
AU - Stefansdottir, Lilja
AU - Skuladottir, Astros Th
AU - Einarsson, Gudmundur
AU - Andresdottir, Margret
AU - Beyter, Doruk
AU - Ferkingstad, Egil
AU - Gretarsdottir, Solveig
AU - Halldorsson, Bjarni V.
AU - Halldorsson, Gisli H.
AU - Helgadottir, Anna
AU - Helgason, Hannes
AU - Hjorleifsson Eldjarn, Grimur
AU - Jonasdottir, Adalbjorg
AU - Jonasdottir, Aslaug
AU - Jonsdottir, Ingileif
AU - Knowlton, Kirk U.
AU - Nadauld, Lincoln D.
AU - Lund, Sigrun H.
AU - Magnusson, Olafur Th
AU - Melsted, Pall
AU - Moore, Kristjan H.S.
AU - Oddsson, Asmundur
AU - Olason, Pall I.
AU - Sigurdsson, Asgeir
AU - Banasik, Karina
AU - Brunak, Søren
AU - Didriksen, Maria
AU - Kogelman, Lisette J.A.
AU - Nielsen, Kaspar R.
AU - Sørensen, Erik
AU - Pedersen, Ole B.
AU - Ullum, Henrik
AU - Bay, Jakob
AU - Burgdorf, Kristoffer
AU - Dowsett, Joseph
AU - Hjalgrim, Henrik
AU - Jacobsen, Rikke L.
AU - Louloudis, Ioannis
AU - Lundgaard, Agnete
AU - Mikkelsen, Christina
AU - Nyegaard, Mette
AU - Henriksen, Alexander P.
AU - Werge, Thomas
AU - Westergaard, David
AU - Olesen, Jes
AU - Ostrowski, Sisse R.
AU - Hansen, Thomas F.
AU - DBDS Genetic Consortium
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.
AB - Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.
U2 - 10.1038/s41588-023-01538-0
DO - 10.1038/s41588-023-01538-0
M3 - Journal article
C2 - 37884687
AN - SCOPUS:85174915851
VL - 55
SP - 1843
EP - 1853
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -
