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PMID: 12945014 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions.

American journal of human genetics ·Vol. 73 ·No. 4 ·2003-10-00 ·Pages 780-90

Seddon JM, Santangelo SL, Book K, Chong S, Cote J

Abstract

We report the results of a genomewide scan for age-related macular degeneration (AMD) in 158 multiplex families. AMD classification was based on fundus photography and was assigned a grade ranging from 1 (no disease) to 5 (exudative disease). Genotyping was performed by the National Heart, Lung, and Blood Institute Mammalian Genotyping Service at Marshfield (404 short tandem repeat markers). The sample included 158 families with two or more siblings with AMD, 490 affected individuals, 101 unaffected individuals, and 38 whose affection status was unknown. Relative pairs included 511 affected sibling, 28 avuncular, 53 cousin, 7 grandparent-grandchild, and 9 grand-avuncular pairs. Two-point parametric and multipoint parametric and nonparametric analyses were performed. Maximum two-point LOD scores of 1.0-2.0 were found for markers on chromosomes 1, 2, 8, 10, 14, 15, and 22. Multipoint analyses were consistent with the two-point results for chromosomes 1, 2, 8, 10, and 22 and provided evidence for additional linkage regions on chromosomes 3, 6, 8, 12, 16, and X. Our signals on chromosomes 1q, 6p, and 10q are consistent with some other previously published results. Significant linkage to AMD was found for one marker on chromosome 2, two adjacent markers on chromosome 3, two adjacent markers on chromosome 6, and seven contiguous markers on chromosome 8, with empirical P values of .00001. The consistency of many of the other signals across both two-point and multipoint, as well as parametric and nonparametric, analyses indicate several other regions worthy of follow-up.

MeSH Terms
Aging/genetics Chromosome Mapping Female Genome, Human Genotype Humans Macular Degeneration/genetics Male Models, Genetic Models, Statistical National Institutes of Health (U.S.) Nuclear Family Reproducibility of Results Siblings Statistics, Nonparametric United States
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Seddon Johanna M
Ophthalmology/Epidemiology Unit, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA. [email protected]
Santangelo Susan L
Book Kathryn
Chong Sandy
Cote Jennifer
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/378505
Email
[email protected]
Published
2003-10-00
Epub
2003-00-22
Pages
780-90
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1180601
Subset
IM
Grants
NEI NIH HHS · R01 EY011309 · United States
NEI NIH HHS · U10 EY011309 · United States
NEI NIH HHS · EY11309 · United States
External Links
PubMed source DOI: 10.1086/378505 PMC Full Text View journal details
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