Abstract
Abstract 15595: Whole Genome Sequencing to Identify Predictors of IVIG Response in Kawasaki Disease
Circulation (New York, N.Y.), Vol.146(Suppl_1), pp.A15595-A15595
11/08/2022
DOI: 10.1161/circ.146.suppl_1.15595
Abstract
Introduction: Kawasaki Disease (KD) leads as a cause of acquired cardiovascular disease among children in developed countries. Around~20% of patients are refractory to high-dose intravenous immunoglobulin (IVIG), the standard treatment, and are at high risk of developing coronary artery aneurysms.
Hypothesis: Whole genome sequencing (WGS) will identify specific predictors of non-response and inform the mechanism of IVIG action.
Methods: KD patients were diagnosed by the American Heart Association and the American Academy of Pediatrics (AHA/AAP) criteria and treated by AHA guidelines. IVIG refractoriness was defined by persistent or recurrent fever (>38C)>36 hours after completing infusion. We performed a case-control study with WGS on DNA from saliva or blood from 107 responders versus 103 non-responders. After processing informatics using the pipeline of Genome Analysis Toolkit (GATK), additive genetic models were assessed for all common variants using logistic regression. We adjusted for age, gender, and race based on principal components. We also conducted SNP-set (Sequence) Kernel Association Test (SKAT) with common and rare variants in the gene regions with the most statistically significant SNP results.
Results: Average sequencing depth was 30x and with a total of 34,548,910 variants. While SNPs in genes previously indicated in the IVIG pathway were confirmed, multiple novel SNPs in various gene regions were also statistically significant (often p< 10-6; Figure-Manhattan plot). SKAT analysis suggested joint effects of multiple SNPs in individual gene regions.
Conclusions: We confirmed SNPs in genes from previous reports and identified multiple novel ones, indicating plausible previous unsuspected IVIG mechanisms pathways. Potentially, functional disruption of these genes could lead to non-response. Further, a panel of these SNPs can be a prognostic tool for identifying at-risk KD patients that require therapy intensification.
Details
- Title: Subtitle
- Abstract 15595: Whole Genome Sequencing to Identify Predictors of IVIG Response in Kawasaki Disease
- Creators
- Sadeep Shrestha - Epidemiology, Birmingham, ALHoward Wiener - University of Alabama at BirminghamHidemi Kajimoto - WAvinodh srinivasasainagendra - University of Alabama at BirminghamDolena Ledee - SEATTLE CHILDRENS RESEARCH INST, Seattle, WASabrina Chowdhury - Epidemiology, Birmingham, ALMikayla Beckley - Seattle Children's Hosp, Arlington, WALuz Padilla - Epidemiology, Birmingham, ALNagib DahdahHemant K Tiwari - University of Alabama at BirminghamMichael A Portman - Seattle Childrens, Seattle, WA
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.146(Suppl_1), pp.A15595-A15595
- DOI
- 10.1161/circ.146.suppl_1.15595
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Publisher
- Lippincott Williams & Wilkins
- Language
- English
- Date published
- 11/08/2022
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984961107102771
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