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 NAA-LADL2 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.
| Original language | English (US) |
|---|---|
| Article number | e0184358 |
| Journal | PLoS One |
| Volume | 12 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2017 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE) : An application to European and Asian cleft palate trios. / Haaland, Øystein A.; Jugessur, Astanand; Gjerdevik, Miriam; Romanowska, Julia; Shi, Min; Beaty, Terri L; Marazita, Mary L.; Murray, Jeffrey C.; Wilcox, Allen J.; Lie, Rolv T.; Gjessing, Håkon K.
In: PLoS One, Vol. 12, No. 9, e0184358, 01.09.2017.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genome-wide analysis of parent-of-origin interaction effects with environmental exposure (PoOxE)
T2 - An application to European and Asian cleft palate trios
AU - Haaland, Øystein A.
AU - Jugessur, Astanand
AU - Gjerdevik, Miriam
AU - Romanowska, Julia
AU - Shi, Min
AU - Beaty, Terri L
AU - Marazita, Mary L.
AU - Murray, Jeffrey C.
AU - Wilcox, Allen J.
AU - Lie, Rolv T.
AU - Gjessing, Håkon K.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 NAA-LADL2 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.
AB - 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 NAA-LADL2 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.
UR - http://www.scopus.com/inward/record.url?scp=85029397319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029397319&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0184358
DO - 10.1371/journal.pone.0184358
M3 - Article
C2 - 28898263
AN - SCOPUS:85029397319
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e0184358
ER -