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American journal of human genetics · 2018

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders.

СтатьяМетаанализПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Ligthart Symen, Vaez Ahmad, Võsa Urmo, Stathopoulou Maria G, de Vries Paul S, Prins Bram P, Van der Most Peter J, Tanaka Toshiko, Naderi Elnaz, Rose Lynda M, Wu Ying, Karlsson Robert, Barbalic Maja, Lin Honghuang, Pool René, Zhu Gu, Macé Aurélien, Sidore Carlo, Trompet Stella, Mangino Massimo, Sabater-Lleal Maria, Kemp John P, Abbasi Ali, Kacprowski Tim, Verweij Niek, Smith Albert V, Huang Tao, Marzi Carola, Feitosa Mary F, Lohman Kurt K, Kleber Marcus E, Milaneschi Yuri, Mueller Christian, Huq Mahmudul, Vlachopoulou Efthymia, Lyytikäinen Leo-Pekka, Oldmeadow Christopher, Deelen Joris, Perola Markus, Zhao Jing Hua, Feenstra Bjarke, LifeLines Cohort Study, Amini Marzyeh, CHARGE Inflammation Working Group, Lahti Jari, Schraut Katharina E, Fornage Myriam, Suktitipat Bhoom, Chen Wei-Min, Li Xiaohui, Nutile Teresa, Malerba Giovanni, Luan Jian'an, Bak Tom, Schork Nicholas, Del Greco M Fabiola, Thiering Elisabeth, Mahajan Anubha, Marioni Riccardo E, Mihailov Evelin, Eriksson Joel, Ozel Ayse Bilge, Zhang Weihua, Nethander Maria, Cheng Yu-Ching, Aslibekyan Stella, Ang Wei, Gandin Ilaria, Yengo Loïc, Portas Laura, Kooperberg Charles, Hofer Edith, Rajan Kumar B, Schurmann Claudia, den Hollander Wouter, Ahluwalia Tarunveer S, Zhao Jing, Draisma Harmen H M, Ford Ian, Timpson Nicholas, Teumer Alexander, Huang Hongyan, Wahl Simone, Liu YongMei, Huang Jie, Uh Hae-Won, Geller Frank, Joshi Peter K, Yanek Lisa R, Trabetti Elisabetta, Lehne Benjamin, Vozzi Diego, Verbanck Marie, Biino Ginevra, Saba Yasaman, Meulenbelt Ingrid, O'Connell Jeff R, Laakso Markku, Giulianini Franco, Magnusson Patrik K E, Ballantyne Christie M, Hottenga Jouke Jan, Montgomery Grant W, Rivadineira Fernando, Rueedi Rico, Steri Maristella, Herzig Karl-Heinz, Stott David J, Menni Cristina, Frånberg Mattias, St Pourcain Beate, Felix Stephan B, Pers Tune H, Bakker Stephan J L, Kraft Peter, Peters Annette, Vaidya Dhananjay, Delgado Graciela, Smit Johannes H, Großmann Vera, Sinisalo Juha, Seppälä Ilkka, Williams Stephen R, Holliday Elizabeth G, Moed Matthijs, Langenberg Claudia, Räikkönen Katri, Ding Jingzhong, Campbell Harry, Sale Michele M, Chen Yii-Der I, James Alan L, Ruggiero Daniela, Soranzo Nicole, Hartman Catharina A, Smith Erin N, Berenson Gerald S, Fuchsberger Christian, Hernandez Dena, Tiesler Carla M T, Giedraitis Vilmantas, Liewald David, Fischer Krista, Mellström Dan, Larsson Anders, Wang Yunmei, Scott William R, Lorentzon Matthias, Beilby John, Ryan Kathleen A, Pennell Craig E, Vuckovic Dragana, Balkau Beverly, Concas Maria Pina, Schmidt Reinhold, Mendes de Leon Carlos F, Bottinger Erwin P, Kloppenburg Margreet, Paternoster Lavinia, Boehnke Michael, Musk A W, Willemsen Gonneke, Evans David M, Madden Pamela A F, Kähönen Mika, Kutalik Zoltán, Zoledziewska Magdalena, Karhunen Ville, Kritchevsky Stephen B, Sattar Naveed, Lachance Genevieve, Clarke Robert, Harris Tamara B, Raitakari Olli T, Attia John R, van Heemst Diana, Kajantie Eero, Sorice Rossella, Gambaro Giovanni, Scott Robert A, Hicks Andrew A, Ferrucci Luigi, Standl Marie, Lindgren Cecilia M, Starr John M, Karlsson Magnus, Lind Lars, Li Jun Z, Chambers John C, Mori Trevor A, de Geus Eco J C N, Heath Andrew C, Martin Nicholas G, Auvinen Juha, Buckley Brendan M, de Craen Anton J M, Waldenberger Melanie, Strauch Konstantin, Meitinger Thomas, Scott Rodney J, McEvoy Mark, Beekman Marian, Bombieri Cristina, Ridker Paul M, Mohlke Karen L, Pedersen Nancy L, Morrison Alanna C, Boomsma Dorret I, Whitfield John B, Strachan David P, Hofman Albert, Vollenweider Peter, Cucca Francesco, Jarvelin Marjo-Riitta, Jukema J Wouter, Spector Tim D, Hamsten Anders, Zeller Tanja, Uitterlinden André G, Nauck Matthias, Gudnason Vilmundur, Qi Lu, Grallert Harald, Borecki Ingrid B, Rotter Jerome I, März Winfried, Wild Philipp S, Lokki Marja-Liisa, Boyle Michael, Salomaa Veikko, Melbye Mads, Eriksson Johan G, Wilson James F, Penninx Brenda W J H, Becker Diane M, Worrall Bradford B, Gibson Greg, Krauss Ronald M, Ciullo Marina, Zaza Gianluigi, Wareham Nicholas J, Oldehinkel Albertine J, Palmer Lyle J, Murray Sarah S, Pramstaller Peter P, Bandinelli Stefania, Heinrich Joachim, Ingelsson Erik, Deary Ian J, Mägi Reedik, Vandenput Liesbeth, van der Harst Pim, Desch Karl C, Kooner Jaspal S, Ohlsson Claes, Hayward Caroline, Lehtimäki Terho, Shuldiner Alan R, Arnett Donna K, Beilin Lawrence J, Robino Antonietta, Froguel Philippe, Pirastu Mario, Jess Tine, Koenig Wolfgang, Loos Ruth J F, Evans Denis A, Schmidt Helena, Smith George Davey, Slagboom P Eline, Eiriksdottir Gudny, Morris Andrew P, Psaty Bruce M, Tracy Russell P, Nolte Ilja M, Boerwinkle Eric, Visvikis-Siest Sophie, Reiner Alex P, Gross Myron, Bis Joshua C, Franke Lude, Franco Oscar H, Benjamin Emelia J, Chasman Daniel I, Dupuis Josée, Snieder Harold, Dehghan Abbas, Alizadeh Behrooz Z

Аннотация

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты