Schwartzman, A. | bioRxiv Science

bioRxiv2018

Peak p-values and false discovery rate inference in neuroimaging

Peaks are a mainstay of neuroimage analysis for reporting localization results. The current peak detection procedure in SPM12 requires a pre-threshold for approximating p-values and a false discovery rate (FDR) nominal level for inference. However, the pre-threshold is an undesirable feature, while the FDR level is meaningless if the signal is assumed to be nonzero everywhere. This article provides: 1) a peak height distribution for smooth Gaussian error fields that does not require a screening pre-threshold; 2) a signal-plus-noise model where FDR of peaks can be controlled and properly interpreted. Matlab code for calculation of p-values using the exact peak height distribution is available as an SPM extension.

neuroscience↗

bioRxiv2017

A simple, consistent estimator of heritability for genome-wide association studies

Analysis of genome-wide association studies (GWAS) is characterized by a large number of univariate regressions where an outcome, a quantitative trait, is regressed on hundreds of thousands to millions of genomic markers, i.e. single-nucleotide polymorphism (SNP) counts, one marker at a time. Assuming a linear model linking the markers to the outcome, this article proposes an estimator of the heritability of the trait, defined here as the fraction of the variance of the trait explained by the genomic markers in the study. The estimator, called GWAS heritability (GWASH) estimator, is easy to compute, highly interpretable, and is consistent as the number of markers and the sample size increase. More importantly, it can be computed from summary statistics typically reported in GWAS, not requiring access to the original data. The estimator takes full account of the linkage disequilibrium (LD) or correlation between the SNPs in the study through moments of the LD matrix, estimable from auxiliary datasets. Unlike other proposed estimators in the literature, the precision of the estimate is obtainable analytically, allowing for power and sample size calculations for heritability estimates.

bioinformatics↗