Saturday, 17 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)
Dankyu Yoon, PhD
,
Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Cheongju, South Korea
Woo-Sung Chang, PhD
,
Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Cheongju, South Korea
Yeon-Seop Kim
,
Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Cheongju, South Korea
Mi-Jin Kang, MS
,
Asan Institute for Life Sciences, Seoul, South Korea
Soo-Jong Hong, MD, PhD
,
Department of Pediatrics, Childhood Asthma Atopy Center, Environmental Health Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Jeom-Kyu Lee, PhD
,
Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Cheongju, South Korea
Eun-Jin Kim, PhD
,
Division of Allergy and Chronic Respiratory Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Cheongju, South Korea
Background: Atopic dermatitis (AD) is a complex and heterogeneous disease influenced by genetic and environmental factors. In the last decade, previous efforts in finding AD associated loci have identified unprecedented amount of associated loci. However, the previously reported genetic loci explain only a small proportion of the heritability. Thus, further analysis on unrevealed genetic component is required to solve the missing heritability problem. In this context, whole-exome sequencing analysis have gathered much attention to find functional variants with relatively high genetic effects. In the present study, we performed whole-exome sequencing study to identify functional variants responsible for severe AD in Korean childhood.
Methods: The case-control samples of 32 severe AD patients and 20 normal individuals were recruited from the Childhood Asthma Atopy Center of Asan Medical Center, diagnosed by physician. The cases and controls were sequenced by Illumina Hi-Seq 2500 with Agilent SureSelectXT Human ALL Exon V4+UTR Kit. Sequence alignment was performed using Burrows-Wheeler Aligner. Variants were called using Genome Analysis Toolkit (GATK). We identified 233,254 single nucleotide variants (SNVs), of which 131,321 SNVs passed quality control criteria (HWE p-value<10-3, Missing rate >10%, Minor allele count <2). Of these, 34,991 variants were non-synonymous SNPs. A Chi-square test was conducted to find disease-associated variants.
Results: We identified three missense variants in a 112bp window at ZNF443(p-value<10-4). For p-value<10-2, 137 missense variants were discovered. Among them, 2 variants at NLRP10 and CYP24A1 were located nearby previously reported AD associated regions. Functional enrichment analysis showed that 47 SNVs were related with immune related genes such as ZBP1, FBXO38, MTR, TTN.
Conclusion:In summary, we identified 137 missense variants susceptible to AD and replicated 2 previously reported loci. To validate the genetic effect of discovered variants, the replication analysis in an independent cohort is required.
