conditional_likelihood.Rdconditional_likelihood is a function which uses summary statistics to
correct bias created by the Winner's Curse phenomenon in the SNP-trait
association estimates, obtained from a discovery GWAS, of SNPs which are
considered significant. The function implements the approximate conditional
likelihood approach, discussed in
Ghosh et
al. (2008), which suggests three different forms of a less biased
association estimate. Note that if the \(z\)-statistic of a particular SNP
is greater than 100, then merely the original naive estimate will be
outputted for the second form of the adjusted estimate, namely
beta.cl2, for that SNP.
conditional_likelihood(summary_data, alpha = 5e-08)A data frame containing summary statistics from the
discovery GWAS. It must have three columns with column names rsid,
beta and se, respectively, and columns beta and
se must contain numerical values. Each row must correspond to a
unique SNP, identified by rsid.
A numerical value which specifies the desired genome-wide
significance threshold. The default is given as 5e-8.
A data frame with summary statistics and adjusted association
estimates of only those SNPs which have been deemed significant according
to the specified threshold, alpha, i.e. SNPs with \(p\)-values
less than alpha. The inputted summary data occupies the first three
columns. The new adjusted association estimates for each SNP, as defined in
the aforementioned paper, are contained in the next three columns, namely
beta.cl1, beta.cl2 and beta.cl3. The SNPs are
contained in this data frame according to their significance, with the most
significant SNP, i.e. the SNP with the largest absolute \(z\)-statistic,
now located in the first row of the data frame. However, if no SNPs are
detected as significant in the data set, conditional_likelihood
returns a warning message: "WARNING: There are no significant SNPs at
this threshold."
Ghosh, A., Zou, F., & Wright, F. A. (2008). Estimating odds ratios in genome scans: an approximate conditional likelihood approach. American journal of human genetics, 82(5), 1064\(-\)1074. doi:10.1016/j.ajhg.2008.03.002
https://amandaforde.github.io/winnerscurse/articles/winners_curse_methods.html
for illustration of the use of conditional_likelihood with a toy data
set and further information regarding the computation of the adjusted
SNP-trait association estimates for significant SNPs.