多遺伝的スコア付けの精度は,遺伝的祖先連続体全体で異なります
Yi Ding1, Kangcheng Hou2, Ziqi Xu3
1Bioinformatics Interdepartmental Program, UCLA, Los Angeles, CA, USA. yiding920@ucla.edu.
Nature
|May 17, 2023
まとめ
多遺伝子スコア (PGS) は,集団内でさえも,遺伝的祖先の精度が低下していることを示しています. 遺伝的距離は PGSのパフォーマンスを 離散的な祖先のラベルよりもよく予測し,連続的なアプローチの必要性を強調しています
科学分野:
- 遺伝学
- バイオ情報学
- 人口の健康
背景:
- 多遺伝子スコア (PGS) は病気のリスクを予測するのに不可欠ですが,多様な集団での移植性には課題があります.
- PGSの移植性に関する現在の評価は,集団内の個々の変化をしばしば無視している.
- PGSの公平な適用は,その一般化が限られているため困難です.
研究 の 目的:
- 多種多様な祖先における多種性スコアの精度に対する遺伝的距離の影響を調査する.
- PGSの移植性について,遺伝的距離の連続的な測定と,離散的な祖先のクラスタの有効性を評価する.
- 集団内および集団間のPGSのパフォーマンスの変動に影響を与える要因を特定する.
主な方法:
- 大規模なバイオバンク (ATLASとUKバイオバンク) を利用し,多様な参加者を集めました.
- PGSの精度を評価した 遺伝的祖先の連続体.
- ピアソン相関を用いて遺伝的距離 (GD) とPGSの精度との関係を定量化した.
- ヨーロッパ系とヒスパニック系/ラテン系アメリカ人の間のPGSパフォーマンスを比較した.
主要な成果:
- PGSの精度は遺伝的祖先の連続に沿って低下し,表面的に均質なグループ内でも減少します.
- 遺伝的距離 (GD) は84の特徴のPGS精度 (r = -0.95) と強く相関しています.
- 訓練データから遺伝的距離が大きい個体は,PGSの精度が著しく低い.
- GDでトレーニングデータに最も近いヒスパニック系/ラテン系個人は,遠いヨーロッパの個人に似たPGSパフォーマンスを示しました.
結論:
- GDで測定される遺伝的祖先の連続性は,PGSの移植性と正確性における重要な要因です.
- PGSの性能を正確に評価し解釈するには,分離された遺伝的祖先のクラスターは不十分です.
- 将来のPSGの開発と適用は,公平な利用のために遺伝的多様性の継続的な性質を考慮する必要があります.
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