433,540人の東アジア人における2型糖尿病の特定
Cassandra N Spracklen1,2, Momoko Horikoshi3, Young Jin Kim4
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nature
|June 6, 2020
まとめ
この研究では,東アジア人群における2型糖尿病 (T2D) リスクに関連した61の新しい遺伝基因が特定されました. この発見は,祖先の間で T2D の共通遺伝因子を強調し,病気の予備性に関する理解を深めています.
科学分野:
- 遺伝学
- 代謝 疾患
- 人口調査
背景:
- 全ゲノム関連研究 (GWAS) では,2型糖尿病 (T2D) のロキュールが240以上,主にヨーロッパの祖先集団で特定されています.
- 東アジア人のT2D傾向に関する遺伝的洞察は限られており,より広範な祖先分析が必要である.
研究 の 目的:
- 東アジアの人口におけるT2Dリスクに関連した新しい遺伝的位置を特定する.
- 東アジアとヨーロッパの祖先の間で共有されたT2Dの遺伝的構造を調査する.
- T2Dに関連した遺伝子,生物学的経路,細胞分化メカニズムを明らかにする.
主な方法:
- 77,418人のT2D症例と356,122人の東アジア出身のコントロールを含むGWASデータの大規模なメタ分析を実施した.
- 体質指数と性別を調整したT2D関連モデルを分析した.
- 発現量的な特徴の位置 (eQTL) データを使用して,特定された位置での遺伝子機能を調査した.
主要な成果:
- 183の場所に301の異なる 関連信号を特定した
- 東アジア人のT2Dの傾向に 関わる61の新しい場所を発見した.
- 東アジアとヨーロッパの集団の両方で一般的なT2D変異の効果サイズが強く相関していることが観察されました.
- GDAP1,PTF1A,SIX3,ALDH2,および筋肉/脂肪分化に関与する遺伝子の近くで,以前に記述されていない関連が報告されています.
- 異なる組織でNKX6-3とANK1に影響する場所でのeQTLを発見した.
結論:
- このGWASメタ解析は,特に東アジアの集団で,既知のT2Dリスクロシウムの数を大幅に拡大しています.
- この発見は,T2Dのような複雑な疾患に対する遺伝的関連研究における多様な祖先集団の重要性を強調しています.
- 新しい遺伝子と経路が特定され,T2Dの病原性を理解し,治療戦略を開発するための新しいターゲットを提供します.
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