Evidence for association between multiple complement pathway genes and AMD

被引:38
作者
Dinu, Valentin
Miller, Perry L.
Zhao, Hongyu
机构
[1] Yale Univ, Sch Med, Ctr Med Informat, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06520 USA
[5] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA
[6] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA
关键词
age related macular degeneration (AMD); complement pathway; false discovery rate (FDR); pathway-based disease association; single nucleotide polymorphisms (SNP);
D O I
10.1002/gepi.20204
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In this paper we explore the use of biological knowledge to supplement statistical analysis in identifying genes associated with disease. It has been previously found that the 402H variant in complement factor H (CFH) is associated with risk for developing age related macular degeneration (AMD). By focusing on the single nucleotide polymorphisms (SNPs) in the complement pathway, we were able to use the genotype data from a recently published AMD genome wide association study to identify two additional genes, C7 and MBL2, as potentially associated with subtypes of AMD. Two SNPs situated in introns of C7 and MBL2 could help differentiate between two forms of AMD: wet (more severe form of AMD) and dry (milder form of AMD). We identified a C7 haplotype associated with protection against developing wet AMD among individuals with homozygous CFH risk allele 402H (p-value 0.001 for wet AMD versus dry AMD, odds ratio (OR) 0.16, OR 95% Cl 0.05-0.49) as well as among individuals with at least one CFH risk allele (p-value 0.007 for wet AMD versus dry AMD, OR 0.35, OR 95% CI 0.16-0.77). The fact that the statistical scores for the C7 and MBL2 SNPs were significant (low false discovery rate) at the pathway level, but not significant at the genome level suggests that focusing at the pathway level can be beneficial for identifying SNP signals that would be lost at the genome-wide level.
引用
收藏
页码:224 / 237
页数:14
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