MendelProb: probability and sample size calculations for Mendelian studies of exome and whole genome sequence data.

TitleMendelProb: probability and sample size calculations for Mendelian studies of exome and whole genome sequence data.
Publication TypeJournal Article
Year of Publication2019
AuthorsHe, Z, Wang, L, DeWan, AT, Leal, SM
JournalBioinformatics
Volume35
Issue3
Pagination529-531
Date Published2019 Feb 01
ISSN1367-4811
Abstract

Motivation: For the design of genetic studies, it is necessary to perform power calculations. Although for Mendelian traits the power of detecting linkage for pedigree(s) can be determined, it is also of great interest to determine the probability of identifying multiple pedigrees or unrelated cases with variants in the same gene. For many diseases, due to extreme locus heterogeneity this probability can be small. If only one family is observed segregating a variant classified as likely pathogenic or of unknown significance, the gene cannot be implicated in disease etiology. The probability of identifying several disease families or cases is dependent on the gene-specific disease prevalence and the sample size. The observation of multiple disease families or cases with variants in the same gene as well as evidence of pathogenicity from other sources, e.g. in silico prediction, expression and functional studies, can aid in implicating a gene in disease etiology. MendelProb can determine the probability of detecting a minimum number of families or cases with variants in the same gene. It can also calculate the probability of detecting genes with variants in different data types, e.g. identifying a variant in at least one family that can establish linkage and more the two additional families regardless of their size. Additionally, for a specified probability MendelProb can determine the number of probands which need to be screened to detect a minimum number of individuals with variants within the same gene.

Results: A single Mendelian disease family is not sufficient to implicate a gene in disease etiology. It is necessary to observe multiple families or cases with potentially pathogenic variants in the same gene. MendelProb, an R library, was developed to determine the probability of observing multiple families and cases with variants within a gene and to also establish the numbers of probands to screen to detect multiple observations of variants within a gene.

Availability and implementation: https://github.com/statgenetics/mendelprob.

DOI10.1093/bioinformatics/bty542
Alternate JournalBioinformatics
PubMed ID30032240
PubMed Central IDPMC6397596
Grant ListR01 DC003594 / DC / NIDCD NIH HHS / United States
R01 HG008972 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States