Genome-wide analysis of common structural variants in Alzheimer's disease identifies a risk-associated regulatory CCG repeat in FAM193B.

A common CCG repeat expansion in FAM193B is significantly associated with increased Alzheimer's disease risk, with an odds ratio of 2.20 per 10-repeat increase.

• Why it matters: Understanding the genetic factors contributing to Alzheimer's disease is crucial, especially beyond known SNPs, as structural variants may explain additional heritability and risk.
• What they did: Using long-read and short-read sequencing data from 3,201 Chinese individuals, the study identified a genome-wide significant association between the FAM193B-CCG repeat expansion and AD risk, and examined its effect on gene expression and brain pathology.
• The result: The expanded FAM193B-CCG repeat increases FAM193B expression, which is linked to DNA damage and cell death pathways in neurons, suggesting its role as a genetic risk factor for AD.