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Chunk #2 — Online Methods — Genotype and Phenotype Data

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Efficient multivariate linear mixed model algorithms for genome-wide association studies.
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The HMDP data includes 100 inbred strains with four phenotypes (high-density lipoprotein, HDL; total cholesterol, TC; triglycerides, TG; unesterified cholesterol, UC) and four million high quality fully imputed SNPs (SNPs are downloaded from http://mouse.cs.ucla.edu/mousehapmap/full.html). We excluded mice with missing phenotypes for any of these four phenotypes. We excluded non-polymorphic SNPs, and SNPs with a minor allele frequency less than 5%. For SNPs that have identical genotypes, we tried to retain only one of them (by using “--indep-pairwise 100 5 0.999999” option in PLINK33). This left us with 98 strains, 656 individuals and 108,562 SNPs. We quantile transformed each phenotype to a standard normal distribution to guard against model mis-specification. We used the product of centered genotype matrix as an estimate of relatedness16,17,34,35. Note that the sample size used here is smaller than the original study31, and the phenotypes are quantile-transformed instead of log transformed for robustness.