ニューロペプチド受容体遺伝子VIPR2の複製は,統合失調症の重大なリスクを伴う
Vladimir Vacic1, Shane McCarthy, Dheeraj Malhotra
1Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 12824, USA.
Nature
|February 25, 2011
まとめ
染色体7q36.3の希少な複製数の増加は統合失調症と関連しています. この発見は,統合失調症の発症における血管活性腸内ペプチドシグナル伝達とVPAC2受容体に関連している.
科学分野:
- 遺伝学 遺伝学とは
- 神経科学は神経科学である.
- 精神科医は精神病を患っている.
背景:
- 希少複製数変種 (CNVs) は神経精神疾患に関与しています.
- 大量のCNVは統合失調症のリスクを大きく引き起こすが,症例のごく一部を占める.
- CNVに関連したリスクの根底にある遺伝子と神経生物学的メカニズムは十分に理解されていません.
研究 の 目的:
- 統合失調症に関連した新種の希少なCNVを特定するために.
- 統合失調症の病原性における特定の遺伝的位置の役割を調査する.
- 統合失調症の潜在的な治療目標を探求する.
主な方法:
- 希少なCNVを検出するための大規模な2段階の全ゲノムスキャンです.
- 統合失調症患者と健康な対照群を比較したケース・コントロール関連研究.
- 7q36.3の362キロベース領域内の複製数変化の分析,VIPR2遺伝子に焦点を当てた.
主要な成果:
- 染色体7q36.3の複製数の増加と統合失調症との間に有意な関連性が見つかりました.
- 7q36.3の微重複,VIPR2の重複または上流は,患者の0.35%で,対照群の0.03%で検出されました.
- 7q36.3 マイクロデプリケーションの患者で観察された,VIPR2 トランスクリプションとサイクルAMPシグナル伝達の増加.
結論:
- 変異した血管活性腸ペプチドシグナリングは,統合失調症の病原性に関与しています.
- VPAC2受容体は,新しい抗精神病薬の開発における潜在的な治療標的である.
- 希少なCNV,特に7q36.3での増加は,統合失調症のリスクに貢献します.
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