MedElevator Войти в исследования
← Поиск публикаций

DOI 10.1038/s41588-023-01538-0

Медицинская библиотека · Nature genetics · 2023

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, Stefansson Olafur A, Saemundsdottir Jona, Sveinbjornsson Gardar, Tragante Vinicius, Unnsteinsdottir Unnur, Walters G Bragi, Zink Florian, Rødevand Linn, Andreassen Ole A, Igland Jannicke, Lie Rolv T, Haavik Jan, Banasik Karina, Brunak Søren, Didriksen Maria, T Bruun Mie, Erikstrup Christian, Kogelman Lisette J A, Nielsen Kaspar R, Sørensen Erik, Pedersen Ole B, Ullum Henrik, DBDS Genetic Consortium, Masson Gisli, Thorsteinsdottir Unnur, Olesen Jes, Ludvigsson Petur, Thorarensen Olafur, Bjornsdottir Anna, Sigurdardottir Gudrun R, Sveinsson Olafur A, Ostrowski Sisse R, Holm Hilma, Gudbjartsson Daniel F, Thorleifsson Gudmar, Sulem Patrick, Stefansson Hreinn, Thorgeirsson Thorgeir E, Hansen Thomas F, Stefansson Kari

СтатьяПоддержка исследования: вне правительства СШАПеревод пока не подготовлен

Аннотация

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.

Для цитирования: 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, Stefansson Olafur A, Saemundsdottir Jona, Sveinbjornsson Gardar, Tragante Vinicius, Unnsteinsdottir Unnur, Walters G Bragi, Zink Florian, Rødevand Linn, Andreassen Ole A, Igland Jannicke, Lie Rolv T, Haavik Jan, Banasik Karina, Brunak Søren, Didriksen Maria, T Bruun Mie, Erikstrup Christian, Kogelman Lisette J A, Nielsen Kaspar R, Sørensen Erik, Pedersen Ole B, Ullum Henrik, DBDS Genetic Consortium, Masson Gisli, Thorsteinsdottir Unnur, Olesen Jes, Ludvigsson Petur, Thorarensen Olafur, Bjornsdottir Anna, Sigurdardottir Gudrun R, Sveinsson Olafur A, Ostrowski Sisse R, Holm Hilma, Gudbjartsson Daniel F, Thorleifsson Gudmar, Sulem Patrick, Stefansson Hreinn, Thorgeirsson Thorgeir E, Hansen Thomas F, Stefansson Kari. Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura.. Nature genetics. 2023. DOI: 10.1038/s41588-023-01538-0.

Предметные рубрики MeSH

HumansGenome-Wide Association StudyMigraine DisordersMigraine with AuraPhenotypeEpilepsy
Подготовка и перевод публикации
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…

История · было → стало

Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.

Тип публикации указан по данным источника. Уровень доказательности автоматически не присваивается.