Parent-of-origin effects on quantitative phenotypes in a large Hutterite pedigree

Sahar V. Mozaffari; Jeanne M. DeCara; Sanjiv J. Shah; Carlo Sidore; Edoardo Fiorillo; Francesco Cucca; Roberto M. Lang; Dan L. Nicolae; Carole Ober

doi:10.1038/s42003-018-0267-4

Parent-of-origin effects on quantitative phenotypes in a large Hutterite pedigree

Sahar V. Mozaffari^*, Jeanne M. DeCara, Sanjiv J. Shah, Carlo Sidore, Edoardo Fiorillo, Francesco Cucca, Roberto M. Lang, Dan L. Nicolae, Carole Ober

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

The impact of the parental origin of associated alleles in GWAS has been largely ignored. Yet sequence variants could affect traits differently depending on whether they are inherited from the mother or the father, as in imprinted regions, where identical inherited DNA sequences can have different effects based on the parental origin. To explore parent-of-origin effects (POEs), we studied 21 quantitative phenotypes in a large Hutterite pedigree to identify variants with single parent (maternal-only or paternal-only) effects, and then variants with opposite parental effects. Here we show that POEs, which can be opposite in direction, are relatively common in humans, have potentially important clinical effects, and will be missed in traditional GWAS. We identified POEs with 11 phenotypes, most of which are risk factors for cardiovascular disease. Many of the loci identified are characteristic of imprinted regions and are associated with the expression of nearby genes.

Original language	English (US)
Article number	28
Journal	Communications Biology
Volume	2
Issue number	1
DOIs	https://doi.org/10.1038/s42003-018-0267-4
State	Published - Dec 1 2019

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
Medicine (miscellaneous)

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title = "Parent-of-origin effects on quantitative phenotypes in a large Hutterite pedigree",

abstract = "The impact of the parental origin of associated alleles in GWAS has been largely ignored. Yet sequence variants could affect traits differently depending on whether they are inherited from the mother or the father, as in imprinted regions, where identical inherited DNA sequences can have different effects based on the parental origin. To explore parent-of-origin effects (POEs), we studied 21 quantitative phenotypes in a large Hutterite pedigree to identify variants with single parent (maternal-only or paternal-only) effects, and then variants with opposite parental effects. Here we show that POEs, which can be opposite in direction, are relatively common in humans, have potentially important clinical effects, and will be missed in traditional GWAS. We identified POEs with 11 phenotypes, most of which are risk factors for cardiovascular disease. Many of the loci identified are characteristic of imprinted regions and are associated with the expression of nearby genes.",

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note = "Funding Information: We thank Catherine Stanhope for help with processing phenotype data, Mark Abney, John Novembre, and members of the Ober lab for useful discussions, Joe Urbanski and Lorenzo Pesce for assistance using Beagle, the many members of our field trip teams for help in phenotyping and collecting and processing samples, and the Hutterites for their continued support of our studies. This work was supported by NIH grants HL085197 and HD21244; and in part by NIH through resources provided by the Computation Institute and the Biological Sciences Division of the University of Chicago and Argonne National Laboratory, under grant 1S10OD018495-01. S.V.M was supported by NIH Grant T32 GM007197 and the Ruth L. Kirschstein NRSA Award F31HL134315. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

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AU - Sidore, Carlo

AU - Fiorillo, Edoardo

AU - Cucca, Francesco

AU - Lang, Roberto M.

AU - Nicolae, Dan L.

AU - Ober, Carole

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N2 - The impact of the parental origin of associated alleles in GWAS has been largely ignored. Yet sequence variants could affect traits differently depending on whether they are inherited from the mother or the father, as in imprinted regions, where identical inherited DNA sequences can have different effects based on the parental origin. To explore parent-of-origin effects (POEs), we studied 21 quantitative phenotypes in a large Hutterite pedigree to identify variants with single parent (maternal-only or paternal-only) effects, and then variants with opposite parental effects. Here we show that POEs, which can be opposite in direction, are relatively common in humans, have potentially important clinical effects, and will be missed in traditional GWAS. We identified POEs with 11 phenotypes, most of which are risk factors for cardiovascular disease. Many of the loci identified are characteristic of imprinted regions and are associated with the expression of nearby genes.

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Parent-of-origin effects on quantitative phenotypes in a large Hutterite pedigree

Abstract

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