インシデント冠動脈疾患の臨床リスクスコアと比較した多遺伝子リスクスコアの予測精度
Jonathan D Mosley1,2, Deepak K Gupta1, Jingyi Tan3
1Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
JAMA
|February 19, 2020
まとめ
多遺伝子リスクスコアは冠動脈疾患 (CHD) の発生と関連しているが,この研究集団における既存の臨床リスク方程式に対する予測は改善しなかった. CHDスクリーニングの臨床的有用性を決定するには,さらなる研究が必要です.
科学分野:
- 遺伝学とゲノミクス
- 心血管疾患の疫学
- 予防的な心臓病
背景:
- 多遺伝的リスクスコア (PRS) は,何百万もの単核酸多形態 (SNP) を利用して,全人口の潜在的冠動脈疾患 (CHD) のスクリーニングを行います.
- 既存の臨床リスク方程式は,CHDリスクを評価するためにガイドラインとして推奨されています.
研究 の 目的:
- PRSが現在の臨床リスク方程式と比較してCHDの予測を向上させるかどうかを評価する.
- 検証されたPRSの予測精度を様々なコホートで評価する.
主な方法:
- 地域における動脈硬化リスク (ARIC) 研究から4847人の成人と,多民族動脈硬化研究 (MESA) から2390人を対象とした遡及コホート研究.
- 国際的な全ゲノム関連研究に基づいた6,630,149のSNPを使用して計算されたPRS.
- 差別化,校正,および純再分類改善 (NRI) を用いた2013年ACC/AHAのプールコホート方程式に対するPRSのパフォーマンスの比較.
主要な成果:
- PRSは,ARICとMESAコホートの両方で10年間のCHD発生率と有意に関連していました.
- PRSをグループ化されたコホート方程式に追加しても,C統計やリスク再分類 (NRI) はいずれのコホートでも有意に改善されなかった.
- PRSはARICまたはMESAコホートにおけるモデルの校正を有意に改善しませんでした.
結論:
- PRSは発作性心血管疾患と関連しているが,一般的な中年白人集団では従来の方法と比較して予測が著しく改善されなかった.
- PRSは現在,この集団におけるCHDのリスク予測を向上させない可能性を示唆しています.
- CHDリスク評価におけるより広範な臨床適用のために,PRSのさらなる検証と精錬が必要である.
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