title: Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is a rare, severe disease resulting from progressive obliteration of small-caliber pulmonary arteries by proliferating vascular cells. PAH can occur without recognized etiology (idiopathic PAH), be associated with a systemic disease or occur as a heritable form, with BMPR2 mutated in approximately 80% of familial and 15% of idiopathic PAH cases. We conducted a genome-wide association study (GWAS) based on 2 independent case-control studies for idiopathic and familial PAH (without BMPR2 mutations), including a total of 625 cases and 1,525 healthy individuals. We detected a significant association at the CBLN2 locus mapping to 18q22.3, with the risk allele conferring an odds ratio for PAH of 1.97 (1.59-2.45; P = 7.47 × 10(-10)). CBLN2 is expressed in the lung, and its expression is higher in explanted lungs from individuals with PAH and in endothelial cells cultured from explanted PAH lungs.
authors.affiliation: Unité Mixte de Recherche en Santé (UMRS) 937, Université Pierre & Marie Curie (UPMC) Université Paris 6 and Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Germain
authors.forename: Mélanie
authors.initials: M
authors.lastname: Eyries
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Odette
authors.initials: O
authors.lastname: Poirier
authors.forename: Barbara
authors.initials: B
authors.lastname: Girerd
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Sophie
authors.initials: S
authors.lastname: Nadaud
authors.forename: Svetlana
authors.initials: S
authors.lastname: Maugenre
authors.forename: Christophe
authors.initials: C
authors.lastname: Guignabert
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.forename: Marilyne
authors.initials: M
authors.lastname: Lévy
authors.forename: Ari
authors.initials: A
authors.lastname: Chaouat
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Lambert
authors.forename: Marion
authors.initials: M
authors.lastname: Bertrand
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuy
authors.forename: Luc
authors.initials: L
authors.lastname: Letenneur
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: Thomy J L
authors.initials: TJ
authors.lastname: de Ravel
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
authors.forename: Eric D
authors.initials: ED
authors.lastname: Austin
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Robbins
authors.forename: Anna R
authors.initials: AR
authors.lastname: Hemnes
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
authors.forename: Erika
authors.initials: E
authors.lastname: Berman-Rosenzweig
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.forename: Gerald
authors.initials: G
authors.lastname: Simonneau
authors.forename: David A
authors.initials: DA
authors.lastname: Trégouët
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
mesh_terms: D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D065627:Familial Primary Pulmonary Hypertension; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D007124:Immunoenzyme Techniques; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger