Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels

Meian He; Marilyn C. Cornelis; Peter Kraft; Rob M. Van Dam; Qi Sun; Cathy C. Laurie; Daniel B. Mirel; Daniel I. Chasman; Paul M. Ridker; David J. Hunter; Frank B. Hu; Lu Qi

doi:10.1161/ATVBAHA.109.199422

Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels

Meian He, Marilyn C. Cornelis, Peter Kraft, Rob M. Van Dam, Qi Sun, Cathy C. Laurie, Daniel B. Mirel, Daniel I. Chasman, Paul M. Ridker, David J. Hunter, Frank B. Hu, Lu Qi^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

Objective: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. Methods and results: We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses' Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1×10^-5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10^-8). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5×10^-8). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels. Conclusion: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

Original language	English (US)
Pages (from-to)	885-890
Number of pages	6
Journal	Arteriosclerosis, thrombosis, and vascular biology
Volume	30
Issue number	4
DOIs	https://doi.org/10.1161/ATVBAHA.109.199422
State	Published - Apr 2010

Keywords

GWA study
IL-18
IL18 gene

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1161/ATVBAHA.109.199422

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He, M., Cornelis, M. C., Kraft, P., Van Dam, R. M., Sun, Q., Laurie, C. C., Mirel, D. B., Chasman, D. I., Ridker, P. M., Hunter, D. J., Hu, F. B., & Qi, L. (2010). Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels. Arteriosclerosis, thrombosis, and vascular biology, 30(4), 885-890. https://doi.org/10.1161/ATVBAHA.109.199422

@article{6d410f50be3743cc88ca9f50ce66a296,

title = "Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels",

abstract = "Objective: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. Methods and results: We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses' Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1×10-5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10-8). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5×10-8). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels. Conclusion: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.",

keywords = "GWA study, IL-18, IL18 gene",

author = "Meian He and Cornelis, {Marilyn C.} and Peter Kraft and {Van Dam}, {Rob M.} and Qi Sun and Laurie, {Cathy C.} and Mirel, {Daniel B.} and Chasman, {Daniel I.} and Ridker, {Paul M.} and Hunter, {David J.} and Hu, {Frank B.} and Lu Qi",

year = "2010",

month = apr,

doi = "10.1161/ATVBAHA.109.199422",

language = "English (US)",

volume = "30",

pages = "885--890",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

issn = "1079-5642",

publisher = "Lippincott Williams and Wilkins",

number = "4",

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He, M, Cornelis, MC, Kraft, P, Van Dam, RM, Sun, Q, Laurie, CC, Mirel, DB, Chasman, DI, Ridker, PM, Hunter, DJ, Hu, FB & Qi, L 2010, 'Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels', Arteriosclerosis, thrombosis, and vascular biology, vol. 30, no. 4, pp. 885-890. https://doi.org/10.1161/ATVBAHA.109.199422

TY - JOUR

T1 - Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels

AU - He, Meian

AU - Cornelis, Marilyn C.

AU - Kraft, Peter

AU - Van Dam, Rob M.

AU - Sun, Qi

AU - Laurie, Cathy C.

AU - Mirel, Daniel B.

AU - Chasman, Daniel I.

AU - Ridker, Paul M.

AU - Hunter, David J.

AU - Hu, Frank B.

AU - Qi, Lu

PY - 2010/4

Y1 - 2010/4

N2 - Objective: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. Methods and results: We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses' Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1×10-5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10-8). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5×10-8). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels. Conclusion: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

AB - Objective: Interleukin-18 (IL-18) is a proinflammatory cytokine involved in the processes of innate and acquired immunities and associated with cardiovascular disease and type 2 diabetes. We sought to identify the common genetic variants associated with IL-18 levels. Methods and results: We performed a 2-stage genome-wide association study among women of European ancestry from the Nurses' Health Study (NHS) and Women's Genome Health Study (WGHS). IL-18 levels were measured by ELISA. In the discovery stage (NHS, n=1523), 7 single-nucleotide polymorphisms (SNPs) at the IL18-BCO2 locus were associated with IL-18 concentrations at the 1×10-5 significance level. The strongest association was found for SNP rs2115763 in the BCO2 gene (P=6.31×10-8). In silico replication in WGHS (435 women) confirmed these findings. The combined analysis of the 2 studies indicated that SNPs rs2115763, rs1834481, and rs7106524 reached a genome-wide significance level (P<5×10-8). Forward selection analysis indicated that SNPs rs2115763 and rs1834481 were independently associated with IL-18 levels (P=0.0002 and 0.0006, respectively). The 2 SNPs together explained 2.9% of variation of plasma IL-18 levels. Conclusion: This study identified several novel variants at the IL18-BCO2 locus associated with IL-18 levels.

KW - GWA study

KW - IL-18

KW - IL18 gene

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DO - 10.1161/ATVBAHA.109.199422

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C2 - 20150558

AN - SCOPUS:77950890497

SN - 1079-5642

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SP - 885

EP - 890

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

IS - 4

ER -

Genome-wide association study identifies variants at the IL18-BCO2 locus associated with interleukin-18 levels

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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