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Updated: Apr 19, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A 2-step penalized regression method for family-based next-generation sequencing association studies
Xiuhua Ding1, Shaoyong Su2, Kannabiran Nandakumar1
1Department of Biostatistics, University of Kentucky College of Public Health, 111 Washington Ave, Lexington, KY 40536-0003, USA.
Abstract:
Large-scale genetic studies are often composed of related participants, and utilizing familial relationships can be cumbersome and computationally challenging. We present an approach to efficiently handle sequencing data from complex pedigrees that incorporates information from rare variants as well as common variants. Our method employs a 2-step procedure that sequentially regresses out correlation from familial relatedness and then uses the resulting phenotypic residuals in a penalized regression framework to test for associations with variants within genetic units. The operating characteristics of this approach are detailed using simulation data based on a large, multigenerational cohort.
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