Unknown

Dataset Information

0

Haplotype-based methods for detecting uncommon causal variants with common SNPs.


ABSTRACT: Detecting uncommon causal variants (minor allele frequency [MAF] < 5%) is difficult with commercial single-nucleotide polymorphism (SNP) arrays that are designed to capture common variants (MAF > 5%). Haplotypes can provide insights into underlying linkage disequilibrium (LD) structure and can tag uncommon variants that are not well tagged by common variants. In this work, we propose a wei-SIMc-matching test that inversely weights haplotype similarities with the estimated standard deviation of haplotype counts to boost the power of similarity-based approaches for detecting uncommon causal variants. We then compare the power of the wei-SIMc-matching test with that of several popular haplotype-based tests, including four other similarity-based tests, a global score test for haplotypes (global), a test based on the maximum score statistic over all haplotypes (max), and two newly proposed haplotype-based tests for rare variant detection. With systematic simulations under a wide range of LD patterns, the results show that wei-SIMc-matching and global are the two most powerful tests. Among these two tests, wei-SIMc-matching has reliable asymptotic P-values, whereas global needs permutations to obtain reliable P-values when the frequencies of some haplotype categories are low or when the trait is skewed. Therefore, we recommend wei-SIMc-matching for detecting uncommon causal variants with surrounding common SNPs, in light of its power and computational feasibility.

SUBMITTER: Lin WY 

PROVIDER: S-EPMC3513398 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Haplotype-based methods for detecting uncommon causal variants with common SNPs.

Lin Wan-Yu WY   Yi Nengjun N   Zhi Degui D   Zhang Kui K   Gao Guimin G   Tiwari Hemant K HK   Liu Nianjun N  

Genetic epidemiology 20120615 6


Detecting uncommon causal variants (minor allele frequency [MAF] < 5%) is difficult with commercial single-nucleotide polymorphism (SNP) arrays that are designed to capture common variants (MAF > 5%). Haplotypes can provide insights into underlying linkage disequilibrium (LD) structure and can tag uncommon variants that are not well tagged by common variants. In this work, we propose a wei-SIMc-matching test that inversely weights haplotype similarities with the estimated standard deviation of h  ...[more]

Similar Datasets

| S-EPMC4155250 | biostudies-literature
| S-EPMC4116485 | biostudies-literature
| S-EPMC2863064 | biostudies-literature
| S-EPMC3669368 | biostudies-literature
| S-EPMC7299304 | biostudies-literature
| S-EPMC2842185 | biostudies-literature
| S-EPMC4945828 | biostudies-literature
| S-EPMC3873500 | biostudies-literature
| S-EPMC4096364 | biostudies-literature
| S-EPMC4131059 | biostudies-literature