Alzheimer's disease: rare variants with large effect sizes

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• 作者：Jorge L Del-Aguila¹ ; ² ; Daniel C Koboldt³ ; Kathleen Black¹ ; ² ; Rachel Chasse¹ ; ² ; Joanne Norton¹ ; ² ; Richard K Wilson³ ; Carlos Cruchaga¹ ; ² ; ^{cruchagc@wustl.edu" class="auth_mail" title="E-mail the corresponding author}
• 刊名：Current Opinion in Genetics & Development
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：33
• 期：Complete
• 页码：49-55
• 全文大小：365 K

文摘

Recent advances in sequencing technology and novel genotyping arrays (focused on low-frequency and coding variants) have made it possible to identify novel coding variants with large effect sizes and also novel genes (TREM2, PLD3, UNC5C, and AKAP9) associated with Alzheimer's disease (AD) risk. The major advantages of these studies over the classic genome-wide association studies (GWAS) include the identification of the functional variant and the gene-driven association. In addition to the large effect size, these studies make it possible to model these variants and genes using cell and animal systems. On the other hand, the underlying population-variability of these very low allele frequency variants poses a great challenge to replicating results. Studies that include very large datasets (>10,000 cases and controls) and combine sequencing and genotyping approaches will lead to the identification of novel genes for Alzheimer's disease.