In:
Annual Review of Genomics and Human Genetics, Annual Reviews, Vol. 15, No. 1 ( 2014-08-31), p. 151-171
Abstract:
Genetic and genomic studies have enhanced our understanding of complex neurodegenerative diseases that exert a devastating impact on individuals and society. One such disease, age-related macular degeneration (AMD), is a major cause of progressive and debilitating visual impairment. Since the pioneering discovery in 2005 of complement factor H (CFH) as a major AMD susceptibility gene, extensive investigations have confirmed 19 additional genetic risk loci, and more are anticipated. In addition to common variants identified by now-conventional genome-wide association studies, targeted genomic sequencing and exome-chip analyses are uncovering rare variant alleles of high impact. Here, we provide a critical review of the ongoing genetic studies and of common and rare risk variants at a total of 20 susceptibility loci, which together explain 40–60% of the disease heritability but provide limited power for diagnostic testing of disease risk. Identification of these susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment.
Type of Medium:
Online Resource
ISSN:
1527-8204
,
1545-293X
DOI:
10.1146/genom.2014.15.issue-1
DOI:
10.1146/annurev-genom-090413-025610
Language:
English
Publisher:
Annual Reviews
Publication Date:
2014
detail.hit.zdb_id:
2033916-1
SSG:
12