双極性障害におけるリチウム治療への反応に関連した遺伝的変異:全ゲノム関連研究
Liping Hou1, Urs Heilbronner2, Franziska Degenhardt3
1Intramural Research Program, National Institute of Mental Health, National Institutes of Health, US Department of Health & Human Services, Bethesda, MD, USA.
Lancet (London, England)
|January 26, 2016
まとめ
双極性障害におけるリチウム反応の遺伝的マーカーは21染色体で特定されました. これらの発見は,パーソナライズされた治療のためのバイオマーカーにつながり,双極性障害の臨床管理を改善します.
科学分野:
- 遺伝学
- 精神科
- ファルマゲノミクス
背景:
- リチウムは双極性障害の主な治療法ですが 患者の反応は大きく異なります
- リチウム治療の有効性に影響する遺伝的要因が疑われる.
- リチウム反応の信頼性の高い遺伝子マーカーを特定する以前の試みは失敗した.
研究 の 目的:
- 双極性障害におけるリチウム反応に関連する遺伝的マーカーを特定するために,全ゲノム関連研究 (GWAS) を実施する.
- 独立したコホートで潜在的な遺伝的発見を検証する.
主な方法:
- 国際リチウム遺伝学コンソーシアム (ConLiGen) の2563人の双極性障害患者を対象とした大規模なGWASです.
- ゲノム全体のゲノタイプ化と帰算を用いた一般的な単一ヌクレオチドポリモルフィズム (SNP) の分析.
- 断定的および連続的なリチウム反応測定法 (アルダスケール) との関連試験
- 研究バッチでの結果のメタ分析と前向きなコホートでの検証
主要な成果:
- 4つのリンクされたSNPを含む21染色体の有意な位置はリチウム反応と関連していました (例えば,rs79663003,p=1. 37×10−8).
- 前向きな研究では,応答関連アレルのキャリアは,有意に低い再発率を示した (p=0. 03268,HR=3. 8).
結論:
- 特定された遺伝領域には,AL157359. 3とAL157359. 4という2つの長い非コーディングRNA (lncRNA) 遺伝子が含まれています.
- LncRNAは,中枢神経系 (CNS) の遺伝子発現の重要な調節体として出現しています.
- これらの発見は,双極性障害における個別化されたリチウム治療のためのバイオマーカーの開発に向けた潜在的なステップであり,その生物学的メカニズムと臨床的有用性に関するさらなる調査を正当化しています.
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