Deletions at 22q11.21 raise Alzheimer risk in early-onset cases, exome study finds
An international team analyzed rare copy-number variants in 22,319 exomes and found deletions in the 22q11.21 chromosomal region were restricted to early-onset Alzheimer disease cases, while duplications at the same locus were more common in controls. The study included 4,150 early-onset patients, 8,519 late-onset patients, and 9,650 unaffected controls. One deletion occurred de novo. Loss-of-function variants in ABCA1 (odds ratio 5.77, p = 0.0002) and ABCA7 (odds ratio 2.29, p = 0.0006) contributed to the deletion burden in early-onset disease. Replication in an independent cohort of 33,977 affected individuals and 362,322 controls confirmed the dosage effect at 22q11.21 with exome-wide significance (odds ratio for SCARF2 = 0.34, p = 5.52 × 10-7).
Deletions at 22q11.21, including those found in DiGeorge syndrome, increase Alzheimer disease risk, while duplications at the same locus appear protective.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].