title: Genome-wide association study identifies five loci associated with lung function.
abstract: Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.
authors.affiliation: Departments of Health Sciences and Genetics, Adrian Building, University of Leicester, Leicester, UK.
authors.forename: Emmanouela
authors.initials: E
authors.lastname: Repapi
authors.forename: Ian
authors.initials: I
authors.lastname: Sayers
authors.forename: Louise V
authors.initials: LV
authors.lastname: Wain
authors.forename: Paul R
authors.initials: PR
authors.lastname: Burton
authors.forename: Toby
authors.initials: T
authors.lastname: Johnson
authors.forename: Ma'en
authors.initials: M
authors.lastname: Obeidat
authors.forename: Jing Hua
authors.initials: JH
authors.lastname: Zhao
authors.forename: Adaikalavan
authors.initials: A
authors.lastname: Ramasamy
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Huffman
authors.forename: Wilmar
authors.initials: W
authors.lastname: Igl
authors.forename: Eva
authors.initials: E
authors.lastname: Albrecht
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: John
authors.initials: J
authors.lastname: Henderson
authors.forename: Raquel
authors.initials: R
authors.lastname: Granell
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.forename: Alicja R
authors.initials: AR
authors.lastname: Rudnicka
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Linda
authors.initials: L
authors.lastname: Mustelin
authors.forename: Taina
authors.initials: T
authors.lastname: Rantanen
authors.forename: Ida
authors.initials: I
authors.lastname: Surakka
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.forename: H Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Ivica
authors.initials: I
authors.lastname: Grkovic
authors.forename: Stipan
authors.initials: S
authors.lastname: Jankovic
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.forename: Asa
authors.initials: A
authors.lastname: Johansson
authors.forename: Ghazal
authors.initials: G
authors.lastname: Zaboli
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Wild
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Sven
authors.initials: S
authors.lastname: Gläser
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Markku
authors.initials: M
authors.lastname: Heliövaara
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Asa Torinsson
authors.initials: AT
authors.lastname: Naluai
authors.forename: Anna-Carin
authors.initials: AC
authors.lastname: Olin
authors.forename: Kjell
authors.initials: K
authors.lastname: Torén
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Cooper
authors.forename: Alan L
authors.initials: AL
authors.lastname: James
authors.forename: Lyle J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: S Goya
authors.initials: SG
authors.lastname: Wannamethee
authors.forename: Peter H
authors.initials: PH
authors.lastname: Whincup
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Shah
authors.initials: S
authors.lastname: Ebrahim
authors.forename: Tricia M
authors.initials: TM
authors.lastname: McKeever
authors.forename: Ian D
authors.initials: ID
authors.lastname: Pavord
authors.forename: Andrew K
authors.initials: AK
authors.lastname: MacLeod
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Morris
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Elaine
authors.initials: E
authors.lastname: Dennison
authors.forename: Seif
authors.initials: S
authors.lastname: Shaheen
authors.forename: Stefan
authors.initials: S
authors.lastname: Karrasch
authors.forename: Eva
authors.initials: E
authors.lastname: Schnabel
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delplanque
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: John D
authors.initials: JD
authors.lastname: Blakey
authors.forename: John R
authors.initials: JR
authors.lastname: Britton
authors.forename: Richard W
authors.initials: RW
authors.lastname: Morris
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.forename: Jennie
authors.initials: J
authors.lastname: Hui
authors.forename: Fredrik
authors.initials: F
authors.lastname: Nyberg
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Jarvelin
authors.forename: Cathy
authors.initials: C
authors.lastname: Jackson
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Probst-Hensch
authors.forename: Beate
authors.initials: B
authors.lastname: Koch
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Ian P
authors.initials: IP
authors.lastname: Hall
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
mesh_terms: D005260:Female; D005541:Forced Expiratory Volume; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D015201:Meta-Analysis as Topic; D008840:Microfilament Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics; D044422:Receptors, Serotonin, 5-HT4 / Q000235:genetics; D012129:Respiratory Function Tests; D013147:Spirometry; D000070876:Tensins; D019699:Thrombospondins / Q000235:genetics; D014797:Vital Capacity
chemical_list: D008840:Microfilament Proteins; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C000603369:TNS1 protein, human; D000070876:Tensins; D019699:Thrombospondins; D044422:Receptors, Serotonin, 5-HT4; D005982:Glutathione Transferase