title: Multicentric Genome-Wide Association Study for Primary Spontaneous Pneumothorax.
abstract: Despite elevated incidence and recurrence rates for Primary Spontaneous Pneumothorax (PSP), little is known about its etiology, and the genetics of idiopathic PSP remains unexplored. To identify genetic variants contributing to sporadic PSP risk, we conducted the first PSP genome-wide association study. Two replicate pools of 92 Portuguese PSP cases and of 129 age- and sex-matched controls were allelotyped in triplicate on the Affymetrix Human SNP Array 6.0 arrays. Markers passing quality control were ranked by relative allele score difference between cases and controls (|RASdiff|), by a novel cluster method and by a combined Z-test. 101 single nucleotide polymorphisms (SNPs) were selected using these three approaches for technical validation by individual genotyping in the discovery dataset. 87 out of 94 successfully tested SNPs were nominally associated in the discovery dataset. Replication of the 87 technically validated SNPs was then carried out in an independent replication dataset of 100 Portuguese cases and 425 controls. The intergenic rs4733649 SNP in chromosome 8 (between LINC00824 and LINC00977) was associated with PSP in the discovery (P = 4.07E-03, ORC[95% CI] = 1.88[1.22-2.89]), replication (P = 1.50E-02, ORC[95% CI] = 1.50[1.08-2.09]) and combined datasets (P = 8.61E-05, ORC[95% CI] = 1.65[1.29-2.13]). This study identified for the first time one genetic risk factor for sporadic PSP, but future studies are warranted to further confirm this finding in other populations and uncover its functional role in PSP pathogenesis.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Inês
authors.identifier: 0000-0001-6983-8870
authors.initials: I
authors.lastname: Sousa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Abrantes
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Vânia
authors.initials: V
authors.lastname: Francisco
authors.affiliation: Hospital Infante Dom Pedro, Aveiro, Portugal.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Teixeira
authors.affiliation: Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Monteiro
authors.affiliation: Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Neves
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Norte
authors.affiliation: Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Robalo Cordeiro
authors.affiliation: Centro Hospitalar de Vila Nova de Gaia, Vila Nova de Gaia, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Moura E Sá
authors.affiliation: Centro Hospitalar do Porto, Porto, Portugal.
authors.forename: Ernestina
authors.initials: E
authors.lastname: Reis
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Santos
authors.affiliation: Universidade de Évora, Évora, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: Hospital de São Bernardo (Centro Hospitalar de Setúbal, E.P.E.), Setúbal, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Sousa
authors.affiliation: Hospital Egas Moniz (Centro Hospitalar de Lisboa Ocidental), Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Fradinho
authors.affiliation: Hospital da Luz, Lisboa, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Malheiro
authors.affiliation: Instituto Português do Sangue e da Transplantacão, Centro Regional de Sangue de Lisboa, Lisboa, Portugal.
authors.forename: Luís
authors.initials: L
authors.lastname: Negrão
authors.affiliation: Hospital de Santa Maria, Lisboa, Portugal.
authors.forename: Salvato
authors.initials: S
authors.lastname: Feijó
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.|Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
mesh_terms: D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D011030:Pneumothorax / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors