Ordered subset linkage analysis supports a susceptibility locus for age-related macular degeneration on chromosome 16p12

BMC Genetics
Silke SchmidtMargaret A Pericak-Vance

Abstract

Age-related macular degeneration (AMD) is a complex disorder that is responsible for the majority of central vision loss in older adults living in developed countries. Phenotypic and genetic heterogeneity complicate the analysis of genome-wide scans for AMD susceptibility loci. The ordered subset analysis (OSA) method is an approach for reducing heterogeneity, increasing statistical power for detecting linkage, and helping to define the most informative data set for follow-up analysis. OSA assesses the linkage evidence in subsets of potentially more homogeneous families by rank-ordering family-specific lod scores with respect to trait-associated covariates or phenotypic features. Here, we present results of incorporating five continuous covariates into our genome-wide linkage analysis of 389 microsatellite markers in 62 multiplex families: Body mass index (BMI), systolic (SBP) and diastolic (DBP) blood pressure, intraocular pressure (IOP), and pack-years of cigarette smoking. Chromosome-wide significance of increases in nonparametric multipoint lod scores in covariate-defined subsets relative to the overall sample was assessed by permutation. Using a correction for testing multiple covariates, statistically significant lod scor...Continue Reading

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Citations

Feb 17, 2010·Journal of Ocular Biology, Diseases, and Informatics·Asako GotoTakeshi Iwata
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Jan 12, 2010·Current Protocols in Human Genetics·William S Bush, Jonathan Haines

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Software Mentioned

PEDCHECK
SAS
Statistical Analysis System (
SIBLINK
OSA
RELPAIR
HOMOG
PREST

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