百万人の退役軍人のプログラムにおける腹動脈動脈瘤の遺伝的構造
Derek Klarin1,2,3,4, Shefali Setia Verma5, Renae Judy6,7
1Malcolm Randall VA Medical Center, Gainesville, FL (D.K., S.T.S., S.A.B.).
Circulation
|September 28, 2020
まとめ
この研究では,腹動脈動脈瘤 (AAA) の14の新しい遺伝的リスク要因が特定され,腹動脈動脈動脈動脈瘤 (AAA) の原因要因として腹動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈動脈 多遺伝的リスクスコアは,AAAの遺伝的リスクが高い個人を特定するのに役立ちます.
科学分野:
- 遺伝学
- 心血管疾患
- 流行病学について
背景:
- 腹動脈動脈瘤 (AAA) は心臓血管死亡の重要な原因である.
- AAAに寄与する遺伝的要因は完全に理解されていませんが,遺伝性の小さな部分を説明するリスクロシウムはわずか10個です.
研究 の 目的:
- 大規模な全ゲノム関連研究を通じて,腹部大動脈瘤 (AAA) の新しい遺伝的決定因子を特定する.
- メンデルのランダム化を用いてAAAの発達における血圧の因果的役割を調査する.
- 多遺伝子リスクスコア (PRS) を開発し,検証し,AAAの遺伝的リスクが高い個人を特定する.
主な方法:
- 約1800万のDNA配列変異体で,百万の退役軍人プログラム (MVP) で全ゲノム関連研究 (GWAS) を実施した.
- 他のコホートで独立複製を行いました
- マンデルのランダム化を用いて,腹動脈と心動脈の血圧がAAAリスクに及ぼす因果関係を評価した.
- 他の血管動脈瘤とのAAAリスク変異の関連性を調べ,29変異の多遺伝子リスクスコア (PRS) を得られた.
主要な成果:
- AAAに関連した14の新しい遺伝的位置を特定し,合計を24にしました.
- 血圧の遺伝的上昇とAAAの発生との因果関係が示された (OR=1. 43,P=1. 6×10−6).
- 29種類のPRSは,家族歴や喫煙に関係なくAAAリスク (OR=1.26,P=2. 7×10−11) を強く予測した.
結論:
- AAAに対する新しい遺伝的関連は治療上の意味を持つ.
- PRSは,家族歴に関係なく,AAAの遺伝的リスクが著しく増加している個人を効果的に特定します.
- PRSをスクリーニングガイドラインに組み込むことで 早期発見と費用対効果が向上します
関連する概念動画
Genome-wide Association Studies-GWAS
12.6K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
12.6K
Thoracic Aorta
2.5K
The thoracic section of the aorta begins at the T5 vertebra and extends to the T12 level at the diaphragm, initially progressing through the mediastinum to the left of the spinal column. Throughout its course in the thoracic segment, the thoracic aorta emits various offshoots known collectively as visceral and parietal branches. The branches that predominantly supply blood to visceral organs are termed visceral branches and include bronchial, pericardial, esophageal, and mediastinal arteries,...
2.5K
Abdominal Aorta
3.5K
Once the aorta traverses the diaphragmatic plane at the aortic hiatus, it is known as the abdominal aorta. This anatomical structure is positioned leftward of the spinal column, encased within a cocoon of adipose tissue behind the peritoneal cavity. It terminates at the L4 vertebra, where it splits into the common iliac arteries. Prior to this bifurcation, the abdominal aorta gives rise to several vital branches.
The celiac trunk, a singular artery, divides into the left gastric artery, which...
The celiac trunk, a singular artery, divides into the left gastric artery, which...
3.5K
Aneurysm I: Introduction
650
An aortic aneurysm is a localized outpouching or dilation at a weak point in the artery wall. It may involve different parts of the aorta, such as the abdominal aorta, aortic arch, or thoracic aorta.Etiological factorsSeveral disorders are associated with aortic aneurysms.Congenital causes, such as primary connective tissue disorders like Marfan syndrome, impact the integrity and strength of connective tissues, notably affecting the aorta. Marfan syndrome is a genetic disorder that specifically...
650
Aneurysm II: Clinical Manifestations and Diagnostic Studies
589
Thoracic, aortic arch and abdominal aneurysms are significant vascular conditions that can present with various clinical manifestations and lead to serious complications. Understanding these manifestations and the appropriate diagnostic studies is essential for effective management and treatment.Thoracic Aortic AneurysmsThoracic aortic aneurysms often remain asymptomatic until they reach a size that impinges on adjacent structures. They typically cause deep, diffuse chest pain that radiates to...
589
Aneurysm III: Interprofessional Care
478
Aneurysm management involves either conservative medical therapy or surgical intervention, depending on the size and symptoms of the aneurysm. Conservative management is generally reserved for smaller, asymptomatic aneurysms, while larger or symptomatic aneurysms often necessitate surgical repair.Conservative Medical TherapyFor small, asymptomatic aneurysms, particularly abdominal aortic aneurysms (AAA) less than 5.5 centimeters in diameter, conservative medical therapy is recommended. This...
478


