Scholarlink

<p>Genome-wide association studies (GWAS) on Alzheimer’s disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (<i>APCDD1</i>) associated with AD. Our WGS analysis was extended to explore the less-characterized genetic factors contributing to AD risk. We identified rare noncoding variants located in cis-regulatory elements specific to excitatory neurons associated with cognitive impairment. Moreover, structural variation analysis showed that short tandem repeat expansion was associated with an increased risk of AD, and copy number variant at the <i>HPSE2</i> locus showed borderline statistical significance. <i>APOE</i> ε4 carriers with high polygenic burden or structural variants exhibited severe cognitive impairment and increased amyloid beta levels, suggesting a cumulative effects model of AD risk.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Whole-genome sequencing analyses suggest novel genetic factors associated with Alzheimer’s disease and a cumulative effects model for risk liability

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月26日

查看全文
  • Jun Pyo Kim,
  • Minyoung Cho,
  • Chanhee Kim,
  • Hyunwoo Lee,
  • Beomjin Jang,
  • Sang-Hyuk Jung,
  • Yujin Kim,
  • In Gyeong Koh,
  • Seoyeon Kim,
  • Daeun Shin,
  • Eun Hye Lee,
  • Jong-Young Lee,
  • YoungChan Park,
  • Hyemin Jang,
  • Bo-Hyun Kim,
  • Hongki Ham,
  • Beomsu Kim,
  • Yujin Kim,
  • A-Hyun Cho,
  • Towfique Raj,
  • Hee Jin Kim,
  • Duk L. Na,
  • Sang Won Seo,
  • Joon-Yong An,
  • Hong-Hee Won

摘要

Genome-wide association studies (GWAS) on Alzheimer’s disease (AD) have predominantly focused on identifying common variants in Europeans. Here, we performed whole-genome sequencing (WGS) of 1,559 individuals from a Korean AD cohort to identify various genetic variants and biomarkers associated with AD. Our GWAS analysis identified a previously unreported locus for common variants (APCDD1) associated with AD. Our WGS analysis was extended to explore the less-characterized genetic factors contributing to AD risk. We identified rare noncoding variants located in cis-regulatory elements specific to excitatory neurons associated with cognitive impairment. Moreover, structural variation analysis showed that short tandem repeat expansion was associated with an increased risk of AD, and copy number variant at the HPSE2 locus showed borderline statistical significance. APOE ε4 carriers with high polygenic burden or structural variants exhibited severe cognitive impairment and increased amyloid beta levels, suggesting a cumulative effects model of AD risk.