講演情報
[BO-3]アトピー性皮膚炎の発症年齢に関する遺伝的特徴の解明
○曳野 圭子1, 田中 奈緒1,2, 小井土 大1,3, 冨塚 耕平1, 小池 良直1, 伊藤 修二1,4, 鈴木 亜香里1, 桃沢 幸秀1, 鎌谷 洋一郎1,3, バイオバンク ジャパン3, 莚田 泰誠1, 寺尾 知可史1,5,6 (1.理化学研究所生命医科学研究センターファーマコゲノミクス研究チーム, 2.東京医科歯科大学, 3.東京大学, 4.島根大学, 5.静岡県立総合病院, 6.静岡県立大学)
While genetic risks for atopic dermatitis (AD) have been reported, genetic attribution based on onset age has not been well investigated; thus, we sought to examine this via the data of our recent genome-wide association studies (GWAS) for AD susceptibility. We found that rs59039403 in NLRP10, a Japanese-specific missense variant, showed a significant association with young onset age among GWAS significant variants with AD susceptibility (p＜5.8x10-4), the risk allele of which accelerated the onset age by 3.28 years. The risk allele counts and genetic risk scores of the GWAS lead variants were significantly negatively correlated with onset age, implying patients with stronger genetic influences tend to have AD at an earlier age. We computed the polygenic risk score (PRS) for AD-susceptibility without the influences of GWAS significant regions and applied to age of onset for AD, resulting in significant negative correlation, which shows not only GWAS significant regions, but also non-significant regions, are polygenically affecting onset age. We also showed the effect sizes of genetic risk for the 17 AD-susceptibility regions differed by onset age, implying the differences in symptoms based on onset age may be due to genetic factors. This first PRS for AD in non-European populations and first investigation of polygenic architecture of onset age of AD suggest associations for AD-susceptibility should be interpreted in age-specific contexts, which could connect to further reveal the pathogenesis of AD based on onset age and stratified early intervention for high-risk patients.