RVS

RVS estimates probabilities of rare variant sharing in extended pedigrees to detect association and linkage between rare genetic variants and dichotomous phenotypes such as disease status.

Key Features:

• Family-Based Sequencing Analysis: Analyzes co-segregation of rare variants among multiple affected individuals within pedigrees, applicable to exome and other sequencing studies.
• Probability Estimation (IBD): Computes the probability that related individuals share rare variants identical-by-descent (IBD) to quantify expected sharing under specific pedigree structures.
• Association and Linkage Testing: Implements statistical tests for both association and linkage between rare variant genotypes and dichotomous phenotypes within family samples.
• Single- and Multi-Variant / Gene-Based Tests: Supports testing individual variants as well as aggregated tests of multiple variants within genomic regions or genes.

Scientific Applications:

• Rare variant discovery in family exome studies: Detects highly penetrant rare variants in exome sequencing pedigree data by evaluating co-segregation with disease phenotypes.
• Complement to population studies: Enhances detection of rare variant–disease associations that are poorly represented in population-based case-control datasets by leveraging within-family sharing and IBD evidence.

Methodology:

Computes likelihoods/probabilities of rare variant sharing identical-by-descent among affected relatives and uses these probabilities as the basis for tests of association and linkage under the null hypothesis.