A discordant sib-pair linkage analysis of age-related macular degeneration.
BACKGROUND
Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness among older adults in the United States and throughout the developed world. Etiological research implicates both genetic and environmental components. Our prior genome scan in 511 affected sib-pairs and other relative pairs identified significant or suggestive linkage signals on chromosomes 1, 2, 3, 6, 8, 10, 12, 16, and 22.


OBJECTIVE
To search for genetic loci for AMD using the extremely discordant sib-pair (EDSP) method of linkage analysis, which until now has never been applied to the study of AMD.


METHODS
The EDSP method is a more powerful approach than standard methods which rely on relative pairs selected at random or pairs concordant for the phenotype. The EDSP approach has also been characterized as the only design that is uniformly powerful in nearly all genetic situations. Thus, substantial reductions in sample size can be achieved.


METHODS
The study sample for analysis included 110 EDSPs from 40 families that comprise a subset of the 158 families studied in a prior genome-wide scan using affected relative pairs.


RESULTS
Evidence for linkage was found on chromosomes 1q, 2q, 6q, 19p, and 20q. The regions identified on chromosomes 1q and 2q were the same regions identified in our prior analysis, whereas the identified region on 6q was approximately 80 cM distal to our previous signal.


CONCLUSIONS
Within this study population, we have narrowed the focus to chromosomes 1q, 2q, 6q, 19p, and 20q in our search for AMD loci. However, given the fact that a gene was recently identified on chromosome 1q, future family- and population-based analyses should concentrate on testing for associations with candidate gene variants in the other identified chromosomal regions in searches for additional AMD loci.
Santangelo
Susan L
SL
Psychiatric & Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, USA. ssantang@psych.mgh.harvard.edu
Yen
Chen-Hsing
CH
Haddad
Stephen
S
Fagerness
Jesen
J
Huang
Christine
C
Seddon
Johanna M
JM
D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007429:Intraocular Pressure; D008126:Lod Score; D008268:Macular Degeneration / Q000235:genetics*; D018895:Microsatellite Repeats; D035781:Siblings