Covariate adjusted inference of parent-of-origin effects using case–control mother–child paired multilocus genotype data

Kai Zhang, Hong Zhang*, Hagit Hochner, Jinbo Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

It is of great interest to identify parent-of-origin effects (POEs) since POEs play an important role in many human heritable disorders and human early life growth and development. POE is sometimes referred to as imprinting effect in the literature. Compared with the standard logistic regression analyses, retrospective likelihood-based statistical methods are more powerful in identifying POEs when data are collected from related individuals retrospectively. However, none of existing retrospective-based methods can appropriately incorporate covariates that should be adjusted for if they are confounding factors. In this paper, a novel semiparametric statistical method, M-HAP, is developed to detect POEs by fully exploring available information from multilocus genotypes of case–control mother–child pairs and covariates. Some large sample properties are established for M-HAP. Finite sample properties of M-HAP are illustrated by extensive simulation studies and real data applications to the Jerusalem Perinatal Study and the Danish National Birth Cohort study, which confirm the desired superiority of M-HAP over some existing methods. M-HAP has been implemented in the updated R package CCMO.

Original languageAmerican English
Pages (from-to)830-847
Number of pages18
JournalGenetic Epidemiology
Volume45
Issue number8
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
We thank two reviewers for their insightful comments. The work of K. Z. and H. Z. was supported by the National Natural Science Foundation of China (No. 11771096, 72091212). The work of J. C. was supported by the National Institutes of Health (Nos. R21‐ES020811, R01‐ES016626). Funding support for the GWAS of Prematurity and its Complications study was provided through the NIH Genes, Environment and Health Initiative (GEI) (U01HG004423). The GWAS of Prematurity and its Complications study is one of the genome‐wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438) and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C).

Funding Information:
We thank two reviewers for their insightful comments. The work of K. Z. and H. Z. was supported by the National Natural Science Foundation of China (No. 11771096, 72091212). The work of J. C. was supported by the National Institutes of Health (Nos. R21-ES020811, R01-ES016626). Funding support for the GWAS of Prematurity and its Complications study was provided through the NIH Genes, Environment and Health Initiative (GEI) (U01HG004423). The GWAS of Prematurity and its Complications study is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438) and the NIH contract ?High throughput genotyping for studying the genetic contributions to human disease? (HHSN268200782096C).

Publisher Copyright:
© 2021 Wiley Periodicals LLC

Keywords

  • case–control study
  • haplotype
  • mother–child pair
  • multilocus genotype
  • parent-of-origin effect
  • case-control study
  • mother-child pair

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