Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors

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• 作者：Ari V. Ahola-Olli¹ ; ^{avahol@utu.fi} ; Peter Wü ; rtz² ; Aki S. Havulinna³ ; Kristiina Aalto⁴ ; Niina Pitk&auml ; nen¹ ; Terho Lehtim&auml ; ki⁵ ; Mika K&auml ; hö ; nen⁶ ; Leo-Pekka Lyytik&auml ; inen⁵ ; Emma Raitoharju⁵ ; Ilkka Sepp&auml ; l&auml ; ⁵ ; Antti-Pekka Sarin³ ; ⁷ ; Samuli Ripatti³ ; ⁷ ; ⁸ ; Aarne Palotie⁷ ; ⁹ ; ¹⁰ ; ¹¹ ; ¹² ; ¹³ ; Markus Perola³ ; ⁷ ; Jorma S. Viikari¹⁴ ; ¹⁵ ; Sirpa Jalkanen⁴ ; Mikael Maksimow⁴ ; Veikko Salomaa³ ; Marko Salmi⁴ ; Johannes Kettunen² ; ³ ; ¹⁶ ; ¹⁷ ; ¹⁹ ; Olli T. Raitakari¹ ; ¹⁷ ; ¹⁸ ; ¹⁹
• 刊名：The American Journal of Human Genetics
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：100
• 期：1
• 页码：40-50
• 全文大小：721 K
• 卷排序：100

文摘

Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p < 1.2 × 10−9) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets.