m+Medelevator.RU
← Поиск публикаций
Cell · 2026

Multi-cohort proteogenomic analyses reveal genetic effects across the proteome and diseasome.

СтатьяНазвание и аннотация: Перевод в очереди
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.

Koprulu Mine, Smith-Byrne Karl, Ferolito Brian Richard, Macdonald-Dunlop Erin, Luan Jian'an, Hedman Åsa K, Ogamba Chibuzor Franklin, Kuliesius Jurgis, Repetto Linda, Ramisch Anna, Abbasi Fahim, Ärnlöv Johan, Assimes Themistocles L, BeLOVE Study Group, Björck Hanna M, Björkander Sophia, Böttcher Morten, Butterworth Adam Stuart, Chen Zhengming, Cho Kelly, Clarke Robert Joseph, Cox Simon Riddington, Czene Kamila, Danesh John, Dedoussis George, Elmståhl Sölve, Eriksson Niclas, Eriksson Per, Esko Tõnu, Estonian Biobank Research Team, Ferreiro-Iglesias Aida, Franks Paul William, Fu Jingyuan, Gaziano J Michael, Ghanbari Mohsen, Gieger Christian, Gilly Arthur, Grallert Harald, Gunter Marc James, Gustafsson Stefan, Göteson Andreas, Hall Per Frans Leonard, Hansson Oskar, Harris Sarah Elizabeth, Hayward Caroline, Herder Christian, Hernandez-Pacheco Natalia, Hijazi Ziad, Hillary Robert F, Hopewell Jemma Caroline, Hu Shixian, Hwang Shih-Jen, Jern Christina, Johansson Åsa, Jonsson Lina, Kalnapenkis Anette, Kerrison Nicola Dorothy, Kho Pik Fang, Klaric Lucija, Kohleick Leonhard, Kraft Julia, Landén Mikael, Levy Daniel, Li Liming, Lind Lars, Long Jirong, Mattsson-Carlgren Niklas, Melén Erik, Merid Simon Kebede, Mertins Philipp, Michaëlsson Karl, Møller Peter Loof, Murgia Federico, Nyegaard Mette, Park Young-Chan, Pearson Ewan, Peters James, Petrie John Ross, Png Grace, Polašek Ozren, Prins Bram Peter, Ripke Stephan, Roden Michael, Rohde Palle Duun, Said Saredo, SCALLOP Consortium, Shen Xia, Schwenk Jochen M, Siegbahn Agneta, Smith J Gustav, Stanne Tara M, Suhre Karsten, Sundström Johan, Thorand Barbara, Valdes-Marquez Elsa, Vallerga Costanza L, van Meurs Joyce B J, Viñuela Ana, Võsa Urmo, Wallentin Lars, Walters Robin G, Wareham Nicholas John, Weber Joachim Eduard, Weersma Rinse Karel, Wilson James F, Winther Simon, Yasmeen Summaira, Zanetti Daniela, Zeggini Eleftheria, Zhao Jing Hua, Zhernakova Alexandra, Zhernakova Daria V, Ziehm Matthias, Kessler Benedikt Mathias, Pereira Alexandre C, Mälarstig Anders, Pietzner Maik, Langenberg Claudia

Аннотация

Understanding the genetic regulation of circulating protein levels can provide new insights into disease mechanisms. Here, we present the largest proteogenomic study to date (n = 78,664 participants across 38 studies), identifying >24,000 protein quantitative trait loci (QTLs) associated with 1,116 proteins, acting near to (n = 5,040) or distant (n = 19,698) from the cognate gene. Using machine learning-guided effector gene assignment, we provide genetic evidence for pathways, cell types, and tissues that modulate circulating protein levels, highlighting N-linked glycosylation as an important regulatory pathway. We demonstrate that genetic instruments of protein production/function ("cis") versus modulation ("trans") reveal distinct phenotypic insights. We identify proteins as candidates for drug targets and engagement (e.g., plasma furin and cardiovascular diseases) by comparing cis-based genetic evidence with protein-disease associations. Systematic triangulation of trans-protein QTLs (pQTLs) with genetic and protein associations across many diseases highlights potential drug repurposing opportunities, e.g., tyrosine kinase 2 (TYK2) inhibitors for rheumatoid arthritis. Our multi-cohort meta-analyses generate proteogenomic insights into disease mechanisms and new treatment opportunities.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты