Opin vísindi

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura


Title: Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura
Author: Bjornsdottir, Gyda   orcid.org/0000-0002-8100-0306
Chalmer, Mona A.
Stefánsdóttir, Lilja
Skuladottir, Astros Th
Einarsson, Gudmundur
Andrésdóttir, Margrét
Beyter, Doruk   orcid.org/0000-0002-3644-5760
Ferkingstad, Egil   orcid.org/0000-0001-8090-7988
Gretarsdottir, Solveig
Halldórsson, Bjarni Vilhjálmur
... 84 more authors Show all authors
Date: 2023-11
Language: English
Scope: 11
University/Institute: Landspitali - The National University Hospital of Iceland
Reykjavik University
School: Health Sciences
Department: Faculty of Industrial Engineering, Mechanical Engineering and Computer Science
Faculty of Medicine
Faculty of Physical Sciences
Series: Nature Genetics; 55(11)
ISSN: 1061-4036
DOI: 10.1038/s41588-023-01538-0
Subject: Barnalæknisfræði; Taugasjúkdómafræði; Humans; Genome-Wide Association Study; Migraine Disorders/genetics; Migraine with Aura/genetics; Phenotype; Epilepsy; Genetics
URI: https://hdl.handle.net/20.500.11815/4539

Show full item record

Citation:

Bjornsdottir , G , Chalmer , M A , Stefánsdóttir , L , Skuladottir , A T , Einarsson , G , Andrésdóttir , M , Beyter , D , Ferkingstad , E , Gretarsdottir , S , Halldórsson , B V , Halldórsson , G H , Helgadottir , A , Helgason , H , Hjorleifsson Eldjarn , G , Jonasdottir , A , Jonasdottir , A , Jónsdóttir , I , Knowlton , K U , Nadauld , L D , Lund , S H , Magnusson , O T , Melsted , P , Moore , K H S , Oddsson , A , Olason , P I , Sigurdsson , A , Stefansson , O A , Saemundsdottir , J , Sveinbjornsson , G , Tragante , V , Unnsteinsdottir , U , Walters , G B , Zink , F , Rødevand , L , Andreassen , O A , Igland , J , Lie , R T , Haavik , J , Banasik , K , Brunak , S , Didriksen , M , T. Bruun , M , Erikstrup , C , Kogelman , L J A , Nielsen , K R , Sørensen , E , Pedersen , O B , Ullum , H , Bay , J , Boldsen , J K , Brodersen , T , Burgdorf , K , Dinh , K M , Dowsett , J , Feenstra , B , Geller , F , Hindhede , L , Hjalgrim , H , Jacobsen , R L , Jemec , G , Kaspersen , K , Kjerulf , B D , Larsen , M A H , Louloudis , I , Lundgaard , A , Mikkelsen , S , Mikkelsen , C , Nissen , I , Nyegaard , M , Henriksen , A P , Rohde , P D , Rostgaard , K , Swinn , M , Thørner , L W , Bruun , M T , Werge , T , Westergaard , D , Masson , G , Þorsteinsdóttir , U , Olesen , J , Ludvigsson , P , Thorarensen , Ó , Bjornsdottir , A , Sigurdardottir , G R , Sveinsson , Ó Á , Ostrowski , S R , Holm , H , Gudbjartsson , D F , Thorleifsson , G , Sulem , P , Stefansson , H , Thorgeirsson , T E , Hansen , T F & Stefánsson , K 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/s41588-023-01538-0

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.

Description:

Publisher Copyright: © 2023, The Author(s).

Files in this item

This item appears in the following Collection(s)