Testing association for markers on the X chromosome

Abstract

Test statistics for association between markers on autosomal chromosomes and a disease have been extensively studied. No research has been reported on performance of such test statistics for association on the X chromosome. With 100,000 or more single-nucleotide polymorphisms (SNPs) available for genome-wide association studies, thousands of them come from the X chromosome. The X chromosome contains rich information about population history and linkage disequilibrium. To identify X-linked marker susceptibility to a disease, it is important to study properties of various statistics that can be used to test for association on the X chromosome. In this article, we compare performance of several approaches for testing association on the X chromosome, and examine how departure from Hardy-Weinberg equilibrium would affect type I error and power of these association tests using X-linked SNPs. The results are applied to the X chromosome of Klein et al. [2005], a genome-wide association study with 100K SNPs for age-related macular degeneration. We found that a SNP (rs10521496) covered by DIAPH2, known to cause premature ovarian failure (POF) in females, is associated with age-related macular degeneration.

Simple strategies for haplotype analysis of the X chromosome with application to age-related macular degeneration

“…Our haplotype analysis of the X chromosome from the GWAS for AMD confirmed the results of the single-marker analysis on the X chromosome for AMD. 1 Moreover, a chromosomal region consisting of five SNPs (rs707289, rs10521496, rs10521495, rs1886894, and rs1012930) has been identified as associated with AMD. A disease-preventive haplotype (ATGAC) on these five SNPs was also identified.…”

“…The top 20% of the SNPs on the X chromosome (360 SNPs) were used for the haplotype analysis using HS tests, although only one of 360 SNPs (rs10521496) was significant after Bonferroni correction, which was also reported before. 1 The distances between some adjacent SNPs on the X chromosome are quite large, which naturally form chromosomal regions. We defined regions so that the distance between any adjacent SNPs is o200 kb.…”

“…1 Hence, we also applied the trainingtesting sets approach. When applying this approach, we randomly chose a quarter of cases and half of controls (24 females with 13 cases, and 25 males with 12 cases).…”

“…Single-marker analysis for the X chromosome has been considered. 1,2 It is well known that haplotype analysis is often more powerful than single-marker analysis. We propose a simple test for haplotype analysis of the X chromosome.…”

No association between the oligodendrocyte-related gene PLP1 and schizophrenia in the Japanese population

“…In detail, HWE can be tested using two null hypotheses: (1) allele frequencies between cases and controls are equal, and (2) HWE holds in females (Zheng et al 2007). Genomic deoxyribonucleic acid (DNA) was extracted from peripheral blood.…”