Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE): An application to European and Asian cleft palate trios

Øystein A Haaland; Astanand Jugessur; Miriam Gjerdevik; Julia Romanowska; Min Shi; Terri H Beaty; Mary L Marazita; Jeffrey C Murray; Allen J Wilcox; Rolv T Lie; Håkon K Gjessing

doi:10.1371/journal.pone.0184358

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Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE): An application to European and Asian cleft palate trios

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Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE): An application to European and Asian cleft palate trios

Øystein A Haaland, Astanand Jugessur, Miriam Gjerdevik, Julia Romanowska, Min Shi, Terri H Beaty, Mary L Marazita, Jeffrey C Murray, Allen J Wilcox, Rolv T Lie, …

PloS one, Vol.12(9), pp.e0184358-e0184358

2017

DOI: 10.1371/journal.pone.0184358

PMCID: PMC5595425

PMID: 28898263

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Abstract

Cleft palate only is a common birth defect with high heritability. Only a small fraction of this heritability is explained by the genetic variants identified so far, underscoring the need to investigate other disease mechanisms, such as gene-environment (GxE) interactions and parent-of-origin (PoO) effects. Furthermore, PoO effects may vary across exposure levels (PoOxE effects). Such variation is the focus of this study. We upgraded the R-package Haplin to enable direct tests of PoOxE effects at the genome-wide level. From a previous GWAS, we had genotypes for 550 case-parent trios, of mainly European and Asian ancestry, and data on three maternal exposures (smoking, alcohol, and vitamins). Data were analyzed for Europeans and Asians separately, and also for all ethnicities combined. To account for multiple testing, a false discovery rate method was used, where q-values were generated from the p-values. In the Europeans-only analyses, interactions with maternal smoking yielded the lowest q-values. Two SNPs in the 'Interactor of little elongation complex ELL subunit 1' (ICE1) gene had a q-value of 0.14, and five of the 20 most significant SNPs were in the 'N-acetylated alpha-linked acidic dipeptidase-like 2' (NAALADL2) gene. No evidence of PoOxE effects was found in the other analyses. The connections to ICE1 and NAALADL2 are novel and warrant further investigation. More generally, the new methodology presented here is easily applicable to other traits and exposures in which a family-based study design has been implemented.

Genome-Wide Association Study

Humans

European Continental Ancestry Group

Male

Cleft Palate - genetics

Gene-Environment Interaction

Cleft Palate - ethnology

Carrier Proteins - genetics

Asian Continental Ancestry Group

Glutamate Carboxypeptidase II - genetics

Alcohol Drinking - epidemiology

Smoking - epidemiology

Maternal Exposure - adverse effects

Female

Avitaminosis - epidemiology

Polymorphism, Single Nucleotide

Cleft Palate - epidemiology

Details

Title: Subtitle: Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE): An application to European and Asian cleft palate trios
Creators: Øystein A Haaland - Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
Astanand Jugessur - Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway
Miriam Gjerdevik - Department of Genetics and Bioinformatics, Norwegian Institute of Public Health (NIPH), Oslo, Norway
Julia Romanowska - Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway
Min Shi - Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences (NIH/NIEHS), Durham, North Carolina, United States of America
Terri H Beaty - Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America
Mary L Marazita - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States of America
Allen J Wilcox - Epidemiology Branch, National Institute of Environmental Health Sciences (NIH/NIEHS), Durham, North Carolina, United States of America
Rolv T Lie - Department of Health Registries, Norwegian Institute of Public Health, Oslo, Norway
Håkon K Gjessing - Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway
Resource Type: Journal article
Publication Details: PloS one, Vol.12(9), pp.e0184358-e0184358
DOI: 10.1371/journal.pone.0184358
PMID: 28898263
PMCID: PMC5595425
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R37 DE008559 / NIDCR NIH HHS R01 DE008559 / NIDCR NIH HHS
Language: English
Date published: 2017
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025315302771

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