DNA methylation within melatonin receptor 1A (MTNR1A) mediates paternally transmitted genetic variant effect on asthma plus rhinitis
Chloé Sarnowski
(1, 2)
,
Catherine Laprise
(3)
,
Giovanni Malerba
(4)
,
Miriam F. Moffatt
(5)
,
Marie-Hélène Dizier
(1, 2)
,
Andréanne Morin
(3, 6)
,
Quentin Vincent
(7, 8)
,
Klaus Rohde
(9, 10)
,
Jorge Esparza-Gordillo
(9)
,
Patricia Margaritte-Jeannin
(1, 2)
,
Liming Liang
(11)
,
Young-Ae Lee
(9)
,
Jean Bousquet
(12)
,
Valérie Siroux
(13)
,
Pier Franco Pignatti
,
William O. C. M. Cookson
(5)
,
Mark Lathrop
(6)
,
Tomi Pastinen
(6)
,
Florence Demenais
(1, 2)
,
Emmanuelle Bouzigon
(1, 2)
1
U946 -
Variabilité Génétique et Maladies Humaines
2 IUH - Institut Universitaire d'Hématologie
3 UQAC - Université du Québec à Chicoutimi
4 UNIVR - Università degli studi di Verona = University of Verona
5 Imperial College London
6 McGill University and Genome Quebec Innovation Centre
7 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
8 UPD5 - Université Paris Descartes - Paris 5
9 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
10 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
11 Harvard School of Public Health
12 Département pneumologie et addictologie [Montpellier]
13 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
2 IUH - Institut Universitaire d'Hématologie
3 UQAC - Université du Québec à Chicoutimi
4 UNIVR - Università degli studi di Verona = University of Verona
5 Imperial College London
6 McGill University and Genome Quebec Innovation Centre
7 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
8 UPD5 - Université Paris Descartes - Paris 5
9 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
10 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
11 Harvard School of Public Health
12 Département pneumologie et addictologie [Montpellier]
13 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
Marie-Hélène Dizier
- Fonction : Auteur
- PersonId : 1117811
- IdHAL : dizier-mh
- ORCID : 0000-0001-8460-7667
Patricia Margaritte-Jeannin
- Fonction : Auteur
- PersonId : 757813
- ORCID : 0000-0003-4442-0026
Jean Bousquet
- Fonction : Auteur
- PersonId : 757330
- ORCID : 0000-0002-4061-4766
Pier Franco Pignatti
- Fonction : Auteur
Résumé
BACKGROUND:
Asthma and allergic rhinitis (AR) are common allergic comorbidities with a strong genetic component in which epigenetic mechanisms might be involved.
OBJECTIVE:
We aimed to identify novel risk loci for asthma and AR while accounting for parent-of-origin effect.
METHODS:
We performed a series of genetic analyses, taking into account the parent-of-origin effect in families ascertained through asthma: (1) genome-wide linkage scan of asthma and AR in 615 European families, (2) association analysis with 1233 single nucleotide polymorphisms (SNPs) covering the significant linkage region in 162 French Epidemiological Study on the Genetics and Environment of Asthma families with replication in 154 Canadian Saguenay-Lac-Saint-Jean asthma study families, and (3) association analysis of disease and significant SNPs with DNA methylation (DNAm) at CpG sites in 40 Saguenay-Lac-Saint-Jean asthma study families.
RESULTS:
We detected a significant paternal linkage of the 4q35 region to asthma and allergic rhinitis comorbidity (AAR; P = 7.2 × 10(-5)). Association analysis in this region showed strong evidence for the effect of the paternally inherited G allele of rs10009104 on AAR (P = 1.1 × 10(-5), reaching the multiple-testing corrected threshold). This paternally inherited allele was also significantly associated with DNAm levels at the cg02303933 site (P = 1.7 × 10(-4)). Differential DNAm at this site was found to mediate the identified SNP-AAR association.
CONCLUSION:
By integrating genetic and epigenetic data, we identified that a differentially methylated CpG site within the melatonin receptor 1A (MTNR1A) gene mediates the effect of a paternally transmitted genetic variant on the comorbidity of asthma and AR. This study provides a novel insight into the role of epigenetic mechanisms in patients with allergic respiratory diseases.
Domaines
AllergologieFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
DNA methylation within melatonin receptor 1A (MTNR1A) mediates paternally transmitted genetic variant effect on asthma plus rhinitis
|
Résumé |
en
BACKGROUND:
Asthma and allergic rhinitis (AR) are common allergic comorbidities with a strong genetic component in which epigenetic mechanisms might be involved.
OBJECTIVE:
We aimed to identify novel risk loci for asthma and AR while accounting for parent-of-origin effect.
METHODS:
We performed a series of genetic analyses, taking into account the parent-of-origin effect in families ascertained through asthma: (1) genome-wide linkage scan of asthma and AR in 615 European families, (2) association analysis with 1233 single nucleotide polymorphisms (SNPs) covering the significant linkage region in 162 French Epidemiological Study on the Genetics and Environment of Asthma families with replication in 154 Canadian Saguenay-Lac-Saint-Jean asthma study families, and (3) association analysis of disease and significant SNPs with DNA methylation (DNAm) at CpG sites in 40 Saguenay-Lac-Saint-Jean asthma study families.
RESULTS:
We detected a significant paternal linkage of the 4q35 region to asthma and allergic rhinitis comorbidity (AAR; P = 7.2 × 10(-5)). Association analysis in this region showed strong evidence for the effect of the paternally inherited G allele of rs10009104 on AAR (P = 1.1 × 10(-5), reaching the multiple-testing corrected threshold). This paternally inherited allele was also significantly associated with DNAm levels at the cg02303933 site (P = 1.7 × 10(-4)). Differential DNAm at this site was found to mediate the identified SNP-AAR association.
CONCLUSION:
By integrating genetic and epigenetic data, we identified that a differentially methylated CpG site within the melatonin receptor 1A (MTNR1A) gene mediates the effect of a paternally transmitted genetic variant on the comorbidity of asthma and AR. This study provides a novel insight into the role of epigenetic mechanisms in patients with allergic respiratory diseases.
|
Auteur(s) |
Chloé Sarnowski
1, 2
, Catherine Laprise
3
, Giovanni Malerba
4
, Miriam F. Moffatt
5
, Marie-Hélène Dizier
1, 2
, Andréanne Morin
3, 6
, Quentin Vincent
7, 8
, Klaus Rohde
9, 10
, Jorge Esparza-Gordillo
9
, Patricia Margaritte-Jeannin
1, 2
, Liming Liang
11
, Young-Ae Lee
9
, Jean Bousquet
12
, Valérie Siroux
13
, Pier Franco Pignatti
, William O. C. M. Cookson
5
, Mark Lathrop
6
, Tomi Pastinen
6
, Florence Demenais
1, 2
, Emmanuelle Bouzigon
1, 2
1
U946 -
Variabilité Génétique et Maladies Humaines
( 81477 )
- Fondation Jean-Dausset-CEPH,
Bâtiment IGM
27 rue Juliette Dodu
75010 Paris
- France
2
IUH -
Institut Universitaire d'Hématologie
( 303086 )
- Université Paris Diderot, 1 Av. Claude Vellefaux 75010 Paris
- France
3
UQAC -
Université du Québec à Chicoutimi
( 300734 )
- 555 Boulevard de l'Université, Chicoutimi, QC G7H 2B1, Canada
- Canada
4
UNIVR -
Università degli studi di Verona = University of Verona
( 542958 )
- Università degli Studi di Verona,
Via dell'Artigliere, 8 -
37129, Verona
- Italie
5
Imperial College London
( 69530 )
- South Kensington Campus, London SW7 2AZ
- Royaume-Uni
6
McGill University and Genome Quebec Innovation Centre
( 322880 )
- 740, Dr. Penfield Avenue, Room 7104
Montréal (Québec)
- Canada
7
IMAGINE - U1163 -
Imagine - Institut des maladies génétiques
( 247401 )
- IHU Imagine,
156 rue de Vaugirard, 75015 PARIS
et
24 Boulevard du Montparnasse, 75015 Paris
- France
8
UPD5 -
Université Paris Descartes - Paris 5
( 301664 )
- 12, rue de l'École de Médecine - 75270 Paris cedex 06
- France
9
MDC -
Max Delbrück Center for Molecular Medicine [Berlin]
( 533514 )
- Robert-Rössle-Straße 10, 13125 Berlin, Allemagne
- Allemagne
10
Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
( 1062372 )
- Charitéplatz 1,
10117 Berlin
- Allemagne
11
Harvard School of Public Health
( 408186 )
- 665 Huntington Ave, Boston, MA 02115
- États-Unis
12
Département pneumologie et addictologie [Montpellier]
( 81964 )
- 371, av. du Doyen Gaston Giraud 34295 Montpellier cedex 5
- France
13
IAB -
Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
( 472784 )
- Institut pour l'Avancée des Biosciences
Centre de Recherche UGA / Inserm U 1209 / CNRS UMR 5309
Site Santé - Allée des Alpes
38700 La Tronche
- France
|
Numéro |
3
|
Page/Identifiant |
748 - 753
|
Volume |
138
|
Comité de lecture |
Oui
|
Vulgarisation |
Non
|
Nom de la revue |
|
Langue du document |
Anglais
|
Audience |
Internationale
|
Date de publication |
2016-09
|
Date de publication électronique |
2016-03-30
|
Domaine(s) |
|
Mots-clés |
en
positional cloning, DNA methylation, parent-of-origin effect, asthma, genetic association study, Linkage analysis, allergic rhinitis
|
DOI | 10.1016/j.jaci.2015.12.1341 |
Pubmed Id | 27038909 |
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