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Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Pubmed ID: 21946350

Authors

  • Soler Artigas M
  • Loth DW
  • Wain LV
  • Gharib SA
  • Obeidat M
  • Tang W
  • Zhai G
  • Zhao JH
  • Smith AV
  • Huffman JE
  • Albrecht E
  • Jackson CM
  • Evans DM
  • Cadby G
  • Fornage M
  • Manichaikul A
  • Lopez LM
  • Johnson T
  • Aldrich MC
  • Aspelund T
  • Barroso I
  • Campbell H
  • Cassano PA
  • Couper DJ
  • Eiriksdottir G
  • Franceschini N
  • Garcia M
  • Gieger C
  • Gislason GK
  • Grkovic I
  • Hammond CJ
  • Hancock DB
  • Harris TB
  • Ramasamy A
  • Heckbert SR
  • Heliövaara M
  • Homuth G
  • Hysi PG
  • James AL
  • Jankovic S
  • Joubert BR
  • Karrasch S
  • Klopp N
  • Koch B
  • Kritchevsky SB
  • Launer LJ
  • Liu Y
  • Loehr LR
  • Lohman K
  • Loos RJ
  • Lumley T
  • Al Balushi KA
  • Ang WQ
  • Barr RG
  • Beilby J
  • Blakey JD
  • Boban M
  • Boraska V
  • Brisman J
  • Britton JR
  • Brusselle GG
  • Cooper C
  • Curjuric I
  • Dahgam S
  • Deary IJ
  • Ebrahim S
  • Eijgelsheim M
  • Francks C
  • Gaysina D
  • Granell R
  • Gu X
  • Hankinson JL
  • Hardy R
  • Harris SE
  • Henderson J
  • Henry A
  • Hingorani AD
  • Hofman A
  • Holt PG
  • Hui J
  • Hunter ML
  • Imboden M
  • Jameson KA
  • Kerr SM
  • Kolcic I
  • Kronenberg F
  • Liu JZ
  • Marchini J
  • McKeever T
  • Morris AD
  • Olin AC
  • Porteous DJ
  • Postma DS
  • Rich SS
  • Ring SM
  • Rivadeneira F
  • Rochat T
  • Sayer AA
  • Sayers I
  • Sly PD
  • Smith GD
  • Sood A
  • Starr JM
  • Uitterlinden AG
  • Vonk JM
  • Wannamethee SG
  • Whincup PH
  • Wijmenga C
  • Williams OD
  • Wong A
  • Mangino M
  • Marciante KD
  • McArdle WL
  • Meibohm B
  • Morrison AC
  • North KE
  • Omenaas E
  • Palmer LJ
  • Pietiläinen KH
  • Pin I
  • Pola Sbreve Ek O
  • Pouta A
  • Psaty BM
  • Hartikainen AL
  • Rantanen T
  • Ripatti S
  • Rotter JI
  • Rudan I
  • Rudnicka AR
  • Schulz H
  • Shin SY
  • Spector TD
  • Surakka I
  • Vitart V
  • Völzke H
  • Wareham NJ
  • Warrington NM
  • Wichmann HE
  • Wild SH
  • Wilk JB
  • Wjst M
  • Wright AF
  • Zgaga L
  • Zemunik T
  • Pennell CE
  • Nyberg F
  • Kuh D
  • Holloway JW
  • Boezen HM
  • Lawlor DA
  • Morris RW
  • Probst-Hensch N
  • International Lung Cancer Consortium
  • GIANT consortium
  • Kaprio J
  • Wilson JF
  • Hayward C
  • Kähönen M
  • Heinrich J
  • Musk AW
  • Jarvis DL
  • Gläser S
  • Järvelin MR
  • Ch Stricker BH
  • Elliott P
  • O'Connor GT
  • Strachan DP
  • London SJ
  • Hall IP
  • Gudnason V
  • Tobin MD

Journal

Nature genetics

Publication Data

November 27, 2011

Associated Grants

  • Agency: Wellcome Trust, Id: 068545/Z/02
  • Agency: Wellcome Trust, Id: 076113/B/04/Z
  • Agency: Wellcome Trust, Id: 077016/Z/05/Z
  • Agency: Wellcome Trust, Id: 079895
  • Agency: Wellcome Trust, Id: 090532
  • Agency: Wellcome Trust, Id: 092731
  • Agency: NHLBI NIH HHS, Id: 1K23HL094531-01
  • Agency: NCI NIH HHS, Id: 1P50 CA70907
  • Agency: NIA NIH HHS, Id: 1R01AG032098-01A1
  • Agency: NIMH NIH HHS, Id: 1RL1MH083268-01
  • Agency: PHS HHS, Id: 268200625226C
  • Agency: PHS HHS, Id: 268200782096C
  • Agency: PHS HHS, Id: 268201100005C
  • Agency: PHS HHS, Id: 268201100006C
  • Agency: PHS HHS, Id: 268201100007C
  • Agency: PHS HHS, Id: 268201100008C
  • Agency: PHS HHS, Id: 268201100009C
  • Agency: PHS HHS, Id: 268201100010C
  • Agency: PHS HHS, Id: 268201100011C
  • Agency: PHS HHS, Id: 268201100012C
  • Agency: NCRR NIH HHS, Id: 5M01 RR00997
  • Agency: NHLBI NIH HHS, Id: 5R01HL087679-02
  • Agency: NIMH NIH HHS, Id: 5R01MH63706:02
  • Agency: NIA NIH HHS, Id: AG-023269
  • Agency: NIA NIH HHS, Id: AG-027058
  • Agency: NIA NIH HHS, Id: AG-15928
  • Agency: NIA NIH HHS, Id: AG-20098
  • Agency: NIA NIH HHS, Id: AG035835
  • Agency: Biotechnology and Biological Sciences Research Council, Id: BB/F019394/1
  • Agency: NCI NIH HHS, Id: CA127219
  • Agency: NCI NIH HHS, Id: CA55769
  • Agency: Chief Scientist Office, Id: CZB/4/710
  • Agency: Chief Scientist Office, Id: CZD/16/6
  • Agency: Chief Scientist Office, Id: CZD/16/6/2
  • Agency: Chief Scientist Office, Id: CZD/16/6/4
  • Agency: NIDDK NIH HHS, Id: DK063491
  • Agency: NIEHS NIH HHS, Id: ES015794
  • Agency: British Heart Foundation, Id: FS05/125
  • Agency: Medical Research Council, Id: G0000934
  • Agency: Medical Research Council, Id: G0401540
  • Agency: Medical Research Council, Id: G0500539
  • Agency: Medical Research Council, Id: G0501942
  • Agency: Medical Research Council, Id: G0600705
  • Agency: Medical Research Council, Id: G0701863
  • Agency: Medical Research Council, Id: G0800582
  • Agency: Medical Research Council, Id: G0801056
  • Agency: Medical Research Council, Id: G0902125
  • Agency: Medical Research Council, Id: G0902313
  • Agency: Medical Research Council, Id: G1000861
  • Agency: Biotechnology and Biological Sciences Research Council, Id: G20234
  • Agency: Medical Research Council, Id: G9815508
  • Agency: Medical Research Council, Id: G9901462
  • Agency: Wellcome Trust, Id: GR069224
  • Agency: NHLBI NIH HHS, Id: HL075336
  • Agency: NHLBI NIH HHS, Id: HL080295
  • Agency: NHLBI NIH HHS, Id: HL087652
  • Agency: NHLBI NIH HHS, Id: HL088133
  • Agency: NHLBI NIH HHS, Id: HL105756
  • Agency: NCRR NIH HHS, Id: M01-RR00425
  • Agency: Medical Research Council, Id: MC_PC_U127561128
  • Agency: Medical Research Council, Id: MC_U106188470
  • Agency: Medical Research Council, Id: MC_U123092720
  • Agency: Medical Research Council, Id: MC_U123092721
  • Agency: Medical Research Council, Id: MC_U127561128
  • Agency: Medical Research Council, Id: MC_UP_A620_1014
  • Agency: Medical Research Council, Id: MC_UP_A620_1015
  • Agency: Canadian Institutes of Health Research, Id: MOP-82893
  • Agency: NHLBI NIH HHS, Id: N01 HC-15103
  • Agency: NHLBI NIH HHS, Id: N01 HC-25195
  • Agency: NHLBI NIH HHS, Id: N01 HC-55222
  • Agency: NHLBI NIH HHS, Id: N01 HC095159
  • Agency: NHLBI NIH HHS, Id: N01-HC-05187
  • Agency: NHLBI NIH HHS, Id: N01-HC-35129
  • Agency: NHLBI NIH HHS, Id: N01-HC-45133
  • Agency: NHLBI NIH HHS, Id: N01-HC-45134
  • Agency: NHLBI NIH HHS, Id: N01-HC-45204
  • Agency: NHLBI NIH HHS, Id: N01-HC-45205
  • Agency: NHLBI NIH HHS, Id: N01-HC-48047
  • Agency: NHLBI NIH HHS, Id: N01-HC-48048
  • Agency: NHLBI NIH HHS, Id: N01-HC-48049
  • Agency: NHLBI NIH HHS, Id: N01-HC-48050
  • Agency: NHLBI NIH HHS, Id: N01-HC-75150
  • Agency: NHLBI NIH HHS, Id: N01-HC-85079
  • Agency: NHLBI NIH HHS, Id: N01-HC-85080
  • Agency: NHLBI NIH HHS, Id: N01-HC-85081
  • Agency: NHLBI NIH HHS, Id: N01-HC-85082
  • Agency: NHLBI NIH HHS, Id: N01-HC-85083
  • Agency: NHLBI NIH HHS, Id: N01-HC-85084
  • Agency: NHLBI NIH HHS, Id: N01-HC-85085
  • Agency: NHLBI NIH HHS, Id: N01-HC-85086
  • Agency: NHLBI NIH HHS, Id: N01-HC-95095
  • Agency: NHLBI NIH HHS, Id: N01-HC-95159
  • Agency: NHLBI NIH HHS, Id: N01-HC-95160
  • Agency: NHLBI NIH HHS, Id: N01-HC-95161
  • Agency: NHLBI NIH HHS, Id: N01-HC-95162
  • Agency: NHLBI NIH HHS, Id: N01-HC-95163
  • Agency: NHLBI NIH HHS, Id: N01-HC-95164
  • Agency: NHLBI NIH HHS, Id: N01-HC-95165
  • Agency: NHLBI NIH HHS, Id: N01-HC-95166
  • Agency: NHLBI NIH HHS, Id: N01-HC-95167
  • Agency: NHLBI NIH HHS, Id: N01-HC-95168
  • Agency: NHLBI NIH HHS, Id: N01-HC-95169
  • Agency: NIA NIH HHS, Id: N01AG12100
  • Agency: NIA NIH HHS, Id: N01AG62101
  • Agency: NIA NIH HHS, Id: N01AG62103
  • Agency: NIA NIH HHS, Id: N01AG62106
  • Agency: NHLBI NIH HHS, Id: N02-HL-6-4278
  • Agency: NCI NIH HHS, Id: P50 CA070907
  • Agency: British Heart Foundation, Id: PG/06/154/22043
  • Agency: British Heart Foundation, Id: PG/97012
  • Agency: NIA NIH HHS, Id: R01 AG032098
  • Agency: NCI NIH HHS, Id: R01 CA121197
  • Agency: NHLBI NIH HHS, Id: R01 HL-071022
  • Agency: NHLBI NIH HHS, Id: R01 HL-074104
  • Agency: NHLBI NIH HHS, Id: R01 HL-077612
  • Agency: NHLBI NIH HHS, Id: R01 HL075476
  • Agency: NHLBI NIH HHS, Id: R01 HL077612
  • Agency: NHLBI NIH HHS, Id: R01-HL-084099
  • Agency: NHLBI NIH HHS, Id: R01-HL084099
  • Agency: NCI NIH HHS, Id: R01CA111703
  • Agency: NHLBI NIH HHS, Id: R01HL071051
  • Agency: NHLBI NIH HHS, Id: R01HL071205
  • Agency: NHLBI NIH HHS, Id: R01HL071250
  • Agency: NHLBI NIH HHS, Id: R01HL071251
  • Agency: NHLBI NIH HHS, Id: R01HL071252
  • Agency: NHLBI NIH HHS, Id: R01HL071258
  • Agency: NHLBI NIH HHS, Id: R01HL071259
  • Agency: NHLBI NIH HHS, Id: R01HL086694
  • Agency: NHLBI NIH HHS, Id: R01HL087641
  • Agency: NHLBI NIH HHS, Id: R01HL59367
  • Agency: NIA NIH HHS, Id: RC1 AG035835
  • Agency: NIA NIH HHS, Id: RC1 AG035835-01
  • Agency: NHLBI NIH HHS, Id: RC1 HL100543
  • Agency: British Heart Foundation, Id: RG/08/013/25942
  • Agency: NCRR NIH HHS, Id: RR-024156
  • Agency: NHGRI NIH HHS, Id: U01-HG-004402
  • Agency: NHGRI NIH HHS, Id: U01-HG-004729
  • Agency: NCI NIH HHS, Id: U19 CA148127
  • Agency: NCRR NIH HHS, Id: UL1RR025005
  • Agency: NIEHS NIH HHS, Id: ZO1 ES49019
  • Agency: Cancer Research UK, Id:
  • Agency: Department of Health, Id:
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Child
  • European Continental Ancestry Group
  • Genome-Wide Association Study
  • Humans
  • Pulmonary Disease, Chronic Obstructive
  • Respiratory Function Tests