Identification of the TIFAB Gene as a Susceptibility Locus for Coronary Artery Aneurysm in Patients with Kawasaki Disease

Korean Kawasaki Disease Genetics Consortium

Research output: Contribution to journalArticle

Abstract

Kawasaki disease (KD) is a self-limiting systemic vasculitis of unknown etiology. KD is often complicated by coronary artery aneurysms (CAAs), which develop in about 20–25% of untreated children and 3–5% of children treated with intravenous immunoglobulin therapy. To identify the risk loci for CAA susceptibility in patients with KD, we performed a genome-wide association study (GWAS) using our previous Illumina HumanOmni1-Quad BeadChip data (296 KD patients) and a new replication study in an independent sample set (713 KD patients) by grouping KD patients without CAA (control) versus KD patients with extremely large aneurysms (diameter ≥ 5 mm) (case). Among 44 candidate single -nucleotide polymorphisms (SNPs) selected from the initial GWAS data (33 cases vs. 215 controls), a SNP (rs899162) located 7 kb upstream of the TIFAB gene on chromosome five was replicated in an independent sample (12 cases vs. 532 controls). In the combined analysis (45 cases vs. 747 controls), the SNP (rs899162) showed a highly significant association with CAA formation (diameter ≥ 5 mm) in patients with KD (odds ratio = 3.20, 95% confidence interval = 2.02–5.05, Pcombined = 1.95 × 10−7). These results indicate that the TIFAB gene may act as a CAA susceptibility locus in patients with KD.

Original languageEnglish
JournalPediatric Cardiology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Coronary Aneurysm
Mucocutaneous Lymph Node Syndrome
Coronary Vessels
Genes
Single Nucleotide Polymorphism
Genome-Wide Association Study
Systemic Vasculitis
Passive Immunization
Intravenous Immunoglobulins
Aneurysm
Chromosomes
Odds Ratio
Confidence Intervals

Keywords

  • Coronary artery aneurysm
  • Genome-wide association study
  • Kawasaki disease
  • Single-nucleotide polymorphism
  • TRAF-interacting protein with FHA domain-containing protein B

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Cardiology and Cardiovascular Medicine

Cite this

Identification of the TIFAB Gene as a Susceptibility Locus for Coronary Artery Aneurysm in Patients with Kawasaki Disease. / Korean Kawasaki Disease Genetics Consortium.

In: Pediatric Cardiology, 01.01.2018.

Research output: Contribution to journalArticle

@article{50050f7f8a1d408e86ac8c7c8c0f7522,
title = "Identification of the TIFAB Gene as a Susceptibility Locus for Coronary Artery Aneurysm in Patients with Kawasaki Disease",
abstract = "Kawasaki disease (KD) is a self-limiting systemic vasculitis of unknown etiology. KD is often complicated by coronary artery aneurysms (CAAs), which develop in about 20–25{\%} of untreated children and 3–5{\%} of children treated with intravenous immunoglobulin therapy. To identify the risk loci for CAA susceptibility in patients with KD, we performed a genome-wide association study (GWAS) using our previous Illumina HumanOmni1-Quad BeadChip data (296 KD patients) and a new replication study in an independent sample set (713 KD patients) by grouping KD patients without CAA (control) versus KD patients with extremely large aneurysms (diameter ≥ 5 mm) (case). Among 44 candidate single -nucleotide polymorphisms (SNPs) selected from the initial GWAS data (33 cases vs. 215 controls), a SNP (rs899162) located 7 kb upstream of the TIFAB gene on chromosome five was replicated in an independent sample (12 cases vs. 532 controls). In the combined analysis (45 cases vs. 747 controls), the SNP (rs899162) showed a highly significant association with CAA formation (diameter ≥ 5 mm) in patients with KD (odds ratio = 3.20, 95{\%} confidence interval = 2.02–5.05, Pcombined = 1.95 × 10−7). These results indicate that the TIFAB gene may act as a CAA susceptibility locus in patients with KD.",
keywords = "Coronary artery aneurysm, Genome-wide association study, Kawasaki disease, Single-nucleotide polymorphism, TRAF-interacting protein with FHA domain-containing protein B",
author = "{Korean Kawasaki Disease Genetics Consortium} and Kwon, {Young Chang} and Kim, {Jae Jung} and Yu, {Jeong Jin} and Yun, {Sin Weon} and Yoon, {Kyung Lim} and Lee, {Kyung Yil} and Kil, {Hong Ryang} and Kim, {Gi Beom} and Han, {Myung Ki} and Song, {Min Seob} and Lee, {Hyoung Doo} and Ha, {Kee Soo} and Sejung Sohn and Hong, {Young Mi} and Giyoung Jang and Lee, {Jong Keuk} and Park, {In Sook} and Hong, {Soo Jong} and Kim, {Kwi Joo} and Hyo-Kyoung Nam and Byeon, {Jung Hye} and Rhim, {Jung Woo} and Kim, {Dong Soo} and Lee, {Jae Moo} and Kim, {Jong Duk}",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00246-018-1992-7",
language = "English",
journal = "Pediatric Cardiology",
issn = "0172-0643",
publisher = "Springer New York",

}

TY - JOUR

T1 - Identification of the TIFAB Gene as a Susceptibility Locus for Coronary Artery Aneurysm in Patients with Kawasaki Disease

AU - Korean Kawasaki Disease Genetics Consortium

AU - Kwon, Young Chang

AU - Kim, Jae Jung

AU - Yu, Jeong Jin

AU - Yun, Sin Weon

AU - Yoon, Kyung Lim

AU - Lee, Kyung Yil

AU - Kil, Hong Ryang

AU - Kim, Gi Beom

AU - Han, Myung Ki

AU - Song, Min Seob

AU - Lee, Hyoung Doo

AU - Ha, Kee Soo

AU - Sohn, Sejung

AU - Hong, Young Mi

AU - Jang, Giyoung

AU - Lee, Jong Keuk

AU - Park, In Sook

AU - Hong, Soo Jong

AU - Kim, Kwi Joo

AU - Nam, Hyo-Kyoung

AU - Byeon, Jung Hye

AU - Rhim, Jung Woo

AU - Kim, Dong Soo

AU - Lee, Jae Moo

AU - Kim, Jong Duk

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Kawasaki disease (KD) is a self-limiting systemic vasculitis of unknown etiology. KD is often complicated by coronary artery aneurysms (CAAs), which develop in about 20–25% of untreated children and 3–5% of children treated with intravenous immunoglobulin therapy. To identify the risk loci for CAA susceptibility in patients with KD, we performed a genome-wide association study (GWAS) using our previous Illumina HumanOmni1-Quad BeadChip data (296 KD patients) and a new replication study in an independent sample set (713 KD patients) by grouping KD patients without CAA (control) versus KD patients with extremely large aneurysms (diameter ≥ 5 mm) (case). Among 44 candidate single -nucleotide polymorphisms (SNPs) selected from the initial GWAS data (33 cases vs. 215 controls), a SNP (rs899162) located 7 kb upstream of the TIFAB gene on chromosome five was replicated in an independent sample (12 cases vs. 532 controls). In the combined analysis (45 cases vs. 747 controls), the SNP (rs899162) showed a highly significant association with CAA formation (diameter ≥ 5 mm) in patients with KD (odds ratio = 3.20, 95% confidence interval = 2.02–5.05, Pcombined = 1.95 × 10−7). These results indicate that the TIFAB gene may act as a CAA susceptibility locus in patients with KD.

AB - Kawasaki disease (KD) is a self-limiting systemic vasculitis of unknown etiology. KD is often complicated by coronary artery aneurysms (CAAs), which develop in about 20–25% of untreated children and 3–5% of children treated with intravenous immunoglobulin therapy. To identify the risk loci for CAA susceptibility in patients with KD, we performed a genome-wide association study (GWAS) using our previous Illumina HumanOmni1-Quad BeadChip data (296 KD patients) and a new replication study in an independent sample set (713 KD patients) by grouping KD patients without CAA (control) versus KD patients with extremely large aneurysms (diameter ≥ 5 mm) (case). Among 44 candidate single -nucleotide polymorphisms (SNPs) selected from the initial GWAS data (33 cases vs. 215 controls), a SNP (rs899162) located 7 kb upstream of the TIFAB gene on chromosome five was replicated in an independent sample (12 cases vs. 532 controls). In the combined analysis (45 cases vs. 747 controls), the SNP (rs899162) showed a highly significant association with CAA formation (diameter ≥ 5 mm) in patients with KD (odds ratio = 3.20, 95% confidence interval = 2.02–5.05, Pcombined = 1.95 × 10−7). These results indicate that the TIFAB gene may act as a CAA susceptibility locus in patients with KD.

KW - Coronary artery aneurysm

KW - Genome-wide association study

KW - Kawasaki disease

KW - Single-nucleotide polymorphism

KW - TRAF-interacting protein with FHA domain-containing protein B

UR - http://www.scopus.com/inward/record.url?scp=85054174521&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054174521&partnerID=8YFLogxK

U2 - 10.1007/s00246-018-1992-7

DO - 10.1007/s00246-018-1992-7

M3 - Article

C2 - 30267110

AN - SCOPUS:85054174521

JO - Pediatric Cardiology

JF - Pediatric Cardiology

SN - 0172-0643

ER -