What question did this study set out to answer?

This research aims to uncover genetic factors contributing to susceptibility to Kawasaki disease (KD).

January 8, 2009PLoS GeneticsOpen Access

A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease

Q: What is the clinical evidence from this study?

Study design: Case-Control. Population: Kawasaki disease (n=2385). Intervention: NAALADL2 rs17531088 variant vs. Reference allele. Primary outcome: Kawasaki disease susceptibility (OR 1.43, 95% CI 1.32-1.53, p=1.13x10^-26).

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Key result

The NAALADL2 rs17531088 variant was significantly associated with increased susceptibility to Kawasaki disease (OR 1.43).

Population

893 Kawasaki disease cases plus population and family controls.

Design

Case-control

Authors

DBDavid BurgnerRoyal Children's Hospital SDSonia DávilaSingHealth WBWillemijn B. BreunisBoston Children's Hospital

Discussion

Member takes

Implication

KD susceptibility loci from this GWAS warrant replication; leaves open any role in pediatric risk stratification or therapy.

Key Points

This research aims to uncover genetic factors contributing to susceptibility to Kawasaki disease (KD).
Performed a genome-wide association study (GWAS) with 119 KD cases and 135 matched controls, followed by replication in an independent cohort of 893 KD cases.
Identified significant associations of 40 SNPs and assessed functional networks using Ingenuity Pathway Analysis.
Measured blood transcript levels of fine-mapped genes during different phases of KD.
Identified two SNPs, NAALADL2 (rs17531088, p(combined) = 1.13 x 10(-6)) and ZFHX3 (rs7199343, p(combined) = 2.37 x 10(-6)), with strong associations to KD.
Functional analysis revealed a significant network involving inflammation and cardiovascular pathology (p = 10(-13)).
Transcripts of associated genes were significantly reduced before treatment in KD cases.

Study Design

Type

Case-Control (n=2,385)

Multicenter

Yes

Structured PICO

Population

893 Caucasian children with Kawasaki disease and 1,492 matched population and family controls evaluated for genetic susceptibility loci.

Comparator

Matched healthy controls and family controls (parents and healthy siblings)

Outcome

Genetic determinants (SNPs and haplotypes) associated with Kawasaki disease susceptibility

Main Result

Odds Ratio: 1.43 (95% CI 1.32–1.53)

p-value: p=1.13x10^-26

This genome-wide association study identified novel susceptibility loci for Kawasaki disease, including variants in NAALADL2 and ZFHX3, highlighting potential functional networks related to inflammation and cardiovascular pathology.

Limitations

Genomic coverage and power of the discovery phase of the GWAS were limited
Relatively modest sample size for a GWAS
Failed to replicate previously reported candidate gene associations

Cite This Study

Burgner et al. (2009) conducted a case-control in Kawasaki disease (n=2,385). NAALADL2 rs17531088 variant vs. Reference allele was evaluated on Kawasaki disease susceptibility (OR 1.43, 95% CI 1.32-1.53, p=1.13x10^-26). The NAALADL2 rs17531088 variant was significantly associated with increased susceptibility to Kawasaki disease (OR 1.43).

synapsesocial.com/papers/6a3f0acabc5541264908ce40 https://doi.org/10.1371/journal.pgen.1000319

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A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

A Genome-Wide Association Study Identifies Novel and Functionally Related Susceptibility Loci for Kawasaki Disease

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Also Consider