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

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

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

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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