2型糖尿病の20791例と24440例の対照群のエクソームシーケンシング
Jason Flannick1,2,3,4, Josep M Mercader5,6,7,8,9, Christian Fuchsberger10,11,12
1Program in Metabolism, Broad Institute, Cambridge, MA, USA. flannick@broadinstitute.org.
Nature
|May 24, 2019
まとめ
4万5千人以上の遺伝子解析により,2型糖尿病 (T2D) リスクに影響を与える希少変種が特定されました. 特定のSLC30A8遺伝子変異はT2Dに対する保護を提供します.
科学分野:
- 遺伝学
- 代謝 疾患
- バイオ情報学
背景:
- タンパク質をコードする遺伝的変異は 病気の病原性についての洞察を与えてくれます
- 2型糖尿病 (T2D) への遺伝的貢献を理解することは,標的治療の開発に不可欠です.
研究 の 目的:
- 2型糖尿病 (T2D) リスクと希少変異の遺伝子レベルの関連性を,エクソーム配列決定を用いて特定する.
- T2Dの遺伝子と薬物標的の優先順位付けにおける希少変異関連の有用性を調査する.
主な方法:
- T2D患者の20791人と,5つの祖先の24440人の非糖尿病の対照群のエクソームシーケンシング.
- 希少変種 (MAF < 0. 5%) とT2Dの遺伝子レベルの関連性を特定するための統計分析.
- T2D薬標的とマウスノックアウト候補を含む遺伝子セットの評価
主要な成果:
- エクソーム全体の有意性で4つの遺伝子の希少変異の遺伝子レベルの関連性を特定した.
- T2Dに対する保護を与える30以上のSLC30A8アレルを発見した.
- T2D薬標的とマウスノックアウト遺伝子を含む 12の遺伝子セットで 重要な関連性が見つかりました
- 珍しい変異のシグナルは,一般的な変異と比較して25%の遺伝性を説明します.
結論:
- 稀な変種,特にSLC30A8は,T2Dの病原化と保護に役割を果たします.
- T2Dの研究のための珍しい変異の関連を解釈し優先させるための新しい方法が提案されています.
- T2D薬の標的における希少変異効果に対するエクソーム全体の有意性を達成するには,大規模なシーケンシングが必要である.
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