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

被引：439

作者：

Ahola-Olli, Ari V. ^{[1
]}

Wurtz, Peter ^{[2
]}

Havulinna, Aki S. ^{[3
]}

Aalto, Kristiina ^{[4
]}

Pitkanen, Niina ^{[1
]}

Lehtimaki, Terho ^{[5
]}

Kahonen, Mika ^{[6
]}

Lyytikainen, Leo-Pekka ^{[5
]}

Raitoharju, Emma ^{[5
]}

Seppala, Ilkka ^{[5
]}

Sarin, Antti-Pekka ^{[3
,7
]}

Ripatti, Samuli ^{[3
,7
,8
]}

Palotie, Aarne ^{[7
,9
,10
,11
,12
,13
]}

Perola, Markus ^{[3
,7
]}

Viikari, Jorma S. ^{[14
,15
]}

Jalkanen, Sirpa ^{[4
]}

Maksimow, Mikael ^{[4
]}

Salomaa, Veikko ^{[3
]}

Salmi, Marko ^{[4
]}

Kettunen, Johannes ^{[2
,3
,16
,17
]}

Raitakari, Olli T. ^{[1
,17
,18
]}

机构：

[1] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland

[2] Univ Oulu, Ctr Life Course Hlth Res, Computat Med, Oulu 90014, Finland

[3] Natl Inst Hlth & Welf, Helsinki 00271, Finland

[4] Univ Turku, Dept Med Microbiol & Immunol, Medic Res Lab, FIN-20520 Turku, Finland

[5] Univ Tampere, Sch Med, Pirkanmaa Hosp Dist, Dept Clin Chem,Fimlab Labs, Tampere 33014, Finland

[6] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland

[7] Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland

[8] Univ Helsinki, Dept Publ Hlth, Helsinki 00271, Finland

[9] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[10] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[11] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[12] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[13] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[14] Univ Turku, Dept Med, FIN-20520 Turku, Finland

[15] Turku Univ Hosp, Div Med, FIN-20520 Turku, Finland

[16] Univ Eastern Finland, Sch Pharm, NMR Metabol Lab, Kuopio 70211, Finland

[17] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland

[18] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2017年 / 100卷 / 01期

基金：

芬兰科学院;

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; DUFFY ANTIGEN RECEPTOR; CROHNS-DISEASE; ULCERATIVE-COLITIS; METAANALYSIS; VARIANTS; INTERLEUKIN-16; IMPUTATION; RISK; INFLAMMATION;

D O I：

10.1016/j.ajhg.2016.11.007

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 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.

引用

页码：40 / 50

页数：11

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