Phred-scaled p-value for exact test of excess heterozygosity (ExcessHet)

### Category Variant Annotations

## Overview

Phred-scaled p-value for exact test of excess heterozygosity.This annotation estimates the probability of the called samples exhibiting excess heterozygosity with respect to the null hypothesis that the samples are unrelated. The higher the score, the higher the chance that the variant is a technical artifact or that there is consanguinuity among the samples. In contrast to Inbreeding Coefficient, there is no minimal number of samples for this annotation. If samples are known to be related, a pedigree file can be provided so that the calculation is only performed on founders and offspring are excluded.

### Statistical notes

This annotation uses the implementation from Wigginton, Cutler, and Abecasis 2005. to calculate a right-sided p-value (the probability of getting the observed number of heterozygotes or higher).

However, note that in releases prior to and including GATK 4.2.3.0, an additional mid-p correction not discussed in that reference was applied. That is, if n_{AB} is the observed number of heterozygous genotypes, N is the total number of samples, and n_A is the number of minor alleles, then the p-value was previously reported as: \sum_{N_{AB} = n_{AB}}^{N} P(N_{AB} | N, n_A) - P(n_{AB} | N, n_A) / 2. Similar mid-p corrections are discussed in e.g. Graffelman and Moreno 2013.

This mid-p correction was removed in subsequent releases, so that the p-value is now reported as: \sum_{N_{AB} = n_{AB}}^{N} P(N_{AB} | N, n_A). This p-value is thus concordant with the P_{high} p-value discussed by Wigginton et al., as well as the ExcHet annotation reported by bcftools.

See discussion at the corresponding GitHub issue and pull request.

### Caveat

The Excess Heterozygosity annotation can only be calculated for diploid samples.

### Related annotations

**InbreedingCoeff** also describes the heterozygosity of the called samples, though without explicitly taking into account the number of samples

GATK version 4.3.0.0 built at Wed, 12 Oct 2022 21:04:44 -0400.

## 0 comments

Please sign in to leave a comment.