Meta-analysis of exome array data identifies six novel genetic loci for lung function

Jackson VE; Latourelle JC; Wain LV; Smith AV; Grove ML; Bartz TM; Obeidat M; Province MA; Gao W; Qaiser B; Porteous DJ; Cassano PA; Ahluwalia TS; Grarup N; Li J; Altmaier E; Marten J; Harris SE; Manichaikul A; Pottinger TD; Li-Gao R; Lind-Thomsen A; Mahajan A; Lahousse L; Imboden M; Teumer A; Prins B; Lyytikäinen LP; Eiriksdottir G; Franceschini N; Sitlani CM; Brody JA; Bossé Y; Timens W; Kraja A; Loukola A; Tang W; Liu Y; Bork-Jensen J; Justesen JM; Linneberg A; Lange LA; Rawal R; Karrasch S; Huffman JE; Smith BH; Davies G; Burkart KM; Mychaleckyj JC; Bonten TN; Enroth S; Lind L; Brusselle GG; Kumar A; Stubbe B; Understanding Society Scientific Group; Kähönen M; Wyss AB; Psaty BM; Heckbert SR; Hao K; Rantanen T; Kritchevsky SB; Lohman K; Skaaby T; Pisinger C; Hansen T; Schulz H; Polasek O; Campbell A; Starr JM; Rich SS; Mook-Kanamori DO; Johansson Å; Ingelsson E; Uitterlinden AG; Weiss S; Raitakari OT; Gudnason V; North KE; Gharib SA; Sin DD; Taylor KD; O'Connor GT; Kaprio J; Harris TB; Pederson O; Vestergaard H; Wilson JG; Strauch K; Hayward C; Kerr S; Deary IJ; Barr RG; de Mutsert R; Gyllensten U; Morris AP; Ikram MA; Probst-Hensch N; Gläser S; Zeggini E; Lehtimäki T; Strachan DP; Dupuis J; Morrison AC; Hall IP; Tobin MD; London SJ
Meta-analysis of exome array data identifies six novel genetic loci for lung function

Jackson VE
Latourelle JC
Wain LV
Smith AV
Grove ML
Bartz TM
Obeidat M
Province MA
Gao W
Qaiser B
Porteous DJ
Cassano PA
Ahluwalia TS
Grarup N
Li J
Altmaier E
Marten J
Harris SE
Manichaikul A
Pottinger TD
Li-Gao R
Lind-Thomsen A
Mahajan A
Lahousse L
Imboden M
Teumer A
Prins B
Lyytikäinen LP
Eiriksdottir G
Franceschini N
Sitlani CM
Brody JA
Bossé Y
Timens W
Kraja A
Loukola A
Tang W
Liu Y
Bork-Jensen J
Justesen JM
Linneberg A
Lange LA
Rawal R
Karrasch S
Huffman JE
Smith BH
Davies G
Burkart KM
Mychaleckyj JC
Bonten TN
Enroth S
Lind L
Brusselle GG
Kumar A
Stubbe B
Understanding Society Scientific Group
Kähönen M
Wyss AB
Psaty BM
Heckbert SR
Hao K
Rantanen T
Kritchevsky SB
Lohman K
Skaaby T
Pisinger C
Hansen T
Schulz H
Polasek O
Campbell A
Starr JM
Rich SS
Mook-Kanamori DO
Johansson Å
Ingelsson E
Uitterlinden AG
Weiss S
Raitakari OT
Gudnason V
North KE
Gharib SA
Sin DD
Taylor KD
O'Connor GT
Kaprio J
Harris TB
Pederson O
Vestergaard H
Wilson JG
Strauch K
Hayward C
Kerr S
Deary IJ
Barr RG
de Mutsert R
Gyllensten U
Morris AP
Ikram MA
Probst-Hensch N
Gläser S
Zeggini E
Lehtimäki T
Strachan DP
Dupuis J
Morrison AC
Hall IP
Tobin MD
London SJ
Katso/Avaa
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doi:10.12688/wellcomeopenres.12583.3
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Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2021042825179
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Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease.
Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals.
Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU.
Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

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