A Pipeline for Phasing and Genotype Imputation on Mixed Human Data (Parents-Offspring Trios and Unrelated Subjects) by Reviewing Current Methods and Software

• Published in: Life (Basel, Switzerland) Vol. 12; no. 12; p. 2030
• Main Authors: Baldrighi, Giulia Nicole, Nova, Andrea, Bernardinelli, Luisa, Fazia, Teresa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.12.2022; MDPI
• Subjects: Accuracy; Algorithms; Association analysis; Computer applications; Data mining; Ethnicity; Families & family life; Genetic markers; Genetic research; Genomes; Genotype; Genotype & phenotype; Genotypes; Haplotypes; Human genetics; imputation pipeline; LD-based method; Methods; mixed data; Multiple imputation (Statistics); Offspring; Open source software; Population; Review; Sample size; Single-nucleotide polymorphism; SNPs; Software; Statistical software; trios; unrelated subjects; Italy; mixed data; SNPs; unrelated subjects; imputation pipeline; LD-based method; trios
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life12122030

Genotype imputation has become an essential prerequisite when performing association analysis. It is a computational technique that allows us to infer genetic markers that have not been directly genotyped, thereby increasing statistical power in subsequent association studies, which consequently has a crucial impact on the identification of causal variants. Many features need to be considered when choosing the proper algorithm for imputation, including the target sample on which it is performed, i.e., related individuals, unrelated individuals, or both. Problems could arise when dealing with a target sample made up of mixed data, composed of both related and unrelated individuals, especially since the scientific literature on this topic is not sufficiently clear. To shed light on this issue, we examined existing algorithms and software for performing phasing and imputation on mixed human data from SNP arrays, specifically when related subjects belong to trios. By discussing the advantages and limitations of the current algorithms, we identified LD-based methods as being the most suitable for reconstruction of haplotypes in this specific context, and we proposed a feasible pipeline that can be used for imputing genotypes in both phased and unphased human data.