Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers

Shah T., Zabaneh D., Gaunt T., Swerdlow D.I., Shah S., Talmud P.J., Day I.N., Whittaker J., Holmes M.V., Sofat R., Humphries S.E., Kivimaki M., Kumari M., Hingorani A.D. and Casas J.P. (2013) Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers. Circulation: Cardiovascular Genetics, 6 2: 163-170. doi:10.1161/CIRCGENETICS.112.964254


Author Shah T.
Zabaneh D.
Gaunt T.
Swerdlow D.I.
Shah S.
Talmud P.J.
Day I.N.
Whittaker J.
Holmes M.V.
Sofat R.
Humphries S.E.
Kivimaki M.
Kumari M.
Hingorani A.D.
Casas J.P.
Title Gene-centric analysis identifies variants associated with interleukin-6 levels and shared pathways with other inflammation markers
Journal name Circulation: Cardiovascular Genetics   Check publisher's open access policy
ISSN 1942-325X
1942-3268
Publication date 2013-04-01
Year available 2013
Sub-type Article (original research)
DOI 10.1161/CIRCGENETICS.112.964254
Open Access Status DOI
Volume 6
Issue 2
Start page 163
End page 170
Total pages 8
Place of publication New York, United States
Publisher Lippincott Williams & Wilkins
Collection year 2014
Language eng
Subject 2705 Cardiology and Cardiovascular Medicine
2716 Genetics (clinical)
1311 Genetics
Formatted abstract
Background-Inflammatory cytokine interleukin-6 (IL-6), a possible risk factor for coronary heart disease, has an estimated heritability of >60%, but to date few genetic variants influencing IL-6 levels are known.

Methods and Results-We used the ITMAT-Broad-Care (IBC) HumanCVD disease BeadChip in the Whitehall II study (N=4911) and British Women's Heart and Health Study (N=3445) to identify single-nucleotide polymorphisms associated with circulating IL-6 levels. Twenty-two single-nucleotide polymorphisms from 7 loci (IL6R/TDRD10, HLA-DRB1, BUD13, SEZ6L, IL1RN, TRIB3, and ABO) were associated with IL-6 (P<10-5), although none were associated with the IL6 gene itself. With the exception of TRIB3, all loci have been previously reported in genome-wide association studies for autoimmune and cardiovascular diseases. Fourteen single-nucleotide polymorphisms in the IL6R region in high-linkage disequilibrium (r2>0.9) with a nonsynonymous variant, rs2228145, were also associated with IL-6 and C-reactive protein concentration (P<10-5). An IL-6-specific weighted allele score explained 2% of the variance of log IL-6 levels (P=2.4410-22) in Whitehall II and 1% (P=1.910-8) in British Women's Heart and Health Studies.

Conclusions-Multiple common genetic variants of modest effect influence IL-6 concentration. Several loci contain single-nucleotide polymorphisms, exhibiting overlapping associations with autoimmune and cardiovascular disorders and other circulating biomarkers. Genetic variants associated with IL-6 provide important tools for probing the causal relevance of IL-6 signaling in a range of cardiometabolic diseases.
Keyword C-reactive protein
Genetic association study
Genetics
Interleukins
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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