Медицинская библиотека · Nature · 2016

Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.

Wahl Simone, Drong Alexander, Lehne Benjamin, Loh Marie, Scott William R, Kunze Sonja, Tsai Pei-Chien, Ried Janina S, Zhang Weihua, Yang Youwen, Tan Sili, Fiorito Giovanni, Franke Lude, Guarrera Simonetta, Kasela Silva, Kriebel Jennifer, Richmond Rebecca C, Adamo Marco, Afzal Uzma, Ala-Korpela Mika, Albetti Benedetta, Ammerpohl Ole, Apperley Jane F, Beekman Marian, Bertazzi Pier Alberto, Black S Lucas, Blancher Christine, Bonder Marc-Jan, Brosch Mario, Carstensen-Kirberg Maren, de Craen Anton J M, de Lusignan Simon, Dehghan Abbas, Elkalaawy Mohamed, Fischer Krista, Franco Oscar H, Gaunt Tom R, Hampe Jochen, Hashemi Majid, Isaacs Aaron, Jenkinson Andrew, Jha Sujeet, Kato Norihiro, Krogh Vittorio, Laffan Michael, Meisinger Christa, Meitinger Thomas, Mok Zuan Yu, Motta Valeria, Ng Hong Kiat, Nikolakopoulou Zacharoula, Nteliopoulos Georgios, Panico Salvatore, Pervjakova Natalia, Prokisch Holger, Rathmann Wolfgang, Roden Michael, Rota Federica, Rozario Michelle Ann, Sandling Johanna K, Schafmayer Clemens, Schramm Katharina, Siebert Reiner, Slagboom P Eline, Soininen Pasi, Stolk Lisette, Strauch Konstantin, Tai E-Shyong, Tarantini Letizia, Thorand Barbara, Tigchelaar Ettje F, Tumino Rosario, Uitterlinden Andre G, van Duijn Cornelia, van Meurs Joyce B J, Vineis Paolo, Wickremasinghe Ananda Rajitha, Wijmenga Cisca, Yang Tsun-Po, Yuan Wei, Zhernakova Alexandra, Batterham Rachel L, Smith George Davey, Deloukas Panos, Heijmans Bastiaan T, Herder Christian, Hofman Albert, Lindgren Cecilia M, Milani Lili, van der Harst Pim, Peters Annette, Illig Thomas, Relton Caroline L, Waldenberger Melanie, Järvelin Marjo-Riitta, Bollati Valentina, Soong Richie, Spector Tim D, Scott James, McCarthy Mark I, Elliott Paul, Bell Jordana T, Matullo Giuseppe, Gieger Christian, Kooner Jaspal S, Grallert Harald, Chambers John C

СтатьяПеревод пока не подготовлен

Аннотация

Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 × 10-7, range P = 9.2 × 10-8 to 6.0 × 10-46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 × 10-6, range P = 5.5 × 10-6 to 6.1 × 10-35, n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 × 10-54). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.

Для цитирования: Wahl Simone, Drong Alexander, Lehne Benjamin, Loh Marie, Scott William R, Kunze Sonja, Tsai Pei-Chien, Ried Janina S, Zhang Weihua, Yang Youwen, Tan Sili, Fiorito Giovanni, Franke Lude, Guarrera Simonetta, Kasela Silva, Kriebel Jennifer, Richmond Rebecca C, Adamo Marco, Afzal Uzma, Ala-Korpela Mika, Albetti Benedetta, Ammerpohl Ole, Apperley Jane F, Beekman Marian, Bertazzi Pier Alberto, Black S Lucas, Blancher Christine, Bonder Marc-Jan, Brosch Mario, Carstensen-Kirberg Maren, de Craen Anton J M, de Lusignan Simon, Dehghan Abbas, Elkalaawy Mohamed, Fischer Krista, Franco Oscar H, Gaunt Tom R, Hampe Jochen, Hashemi Majid, Isaacs Aaron, Jenkinson Andrew, Jha Sujeet, Kato Norihiro, Krogh Vittorio, Laffan Michael, Meisinger Christa, Meitinger Thomas, Mok Zuan Yu, Motta Valeria, Ng Hong Kiat, Nikolakopoulou Zacharoula, Nteliopoulos Georgios, Panico Salvatore, Pervjakova Natalia, Prokisch Holger, Rathmann Wolfgang, Roden Michael, Rota Federica, Rozario Michelle Ann, Sandling Johanna K, Schafmayer Clemens, Schramm Katharina, Siebert Reiner, Slagboom P Eline, Soininen Pasi, Stolk Lisette, Strauch Konstantin, Tai E-Shyong, Tarantini Letizia, Thorand Barbara, Tigchelaar Ettje F, Tumino Rosario, Uitterlinden Andre G, van Duijn Cornelia, van Meurs Joyce B J, Vineis Paolo, Wickremasinghe Ananda Rajitha, Wijmenga Cisca, Yang Tsun-Po, Yuan Wei, Zhernakova Alexandra, Batterham Rachel L, Smith George Davey, Deloukas Panos, Heijmans Bastiaan T, Herder Christian, Hofman Albert, Lindgren Cecilia M, Milani Lili, van der Harst Pim, Peters Annette, Illig Thomas, Relton Caroline L, Waldenberger Melanie, Järvelin Marjo-Riitta, Bollati Valentina, Soong Richie, Spector Tim D, Scott James, McCarthy Mark I, Elliott Paul, Bell Jordana T, Matullo Giuseppe, Gieger Christian, Kooner Jaspal S, Grallert Harald, Chambers John C. Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity.. Nature. 2016. DOI: 10.1038/nature20784.

Предметные рубрики MeSH

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.

Аннотация

Предметные рубрики MeSH

Ошибки и ограничения