Table 1:
Genes implicated using gene expression data, protein level data and functional annotation
| Gene | Phenotype | Other traits | Novel Tier/ Previous | Sentinel SNP | Position (b37) | COPD risk/alt | Functionally implicated genes |
|---|---|---|---|---|---|---|---|
| DHDDS (intron) | FVC | FEV1 | Tier 2 | rs9438626 | 1:26,775,367 | G/C | DHDDS† |
| DHDDS (3’-UTR) | FEV1 | Tier 1 | rs12096239 | 1:26,796,922 | C/G | HMGN2†, DHDDS† | |
| NEXN (intron) | FEV1/FVC | Tier 1 | rs9661687 | 1:78,387,270 | T/C | NEXN† | |
| DENND2D (intron) | FEV1/FVC | FEV1 | Tier 1 | rs9970286 | 1:111,737,398 | G/A | CEPT1†, CHI3L2†, DRAM2† |
| C1orf54 (intron) | PEF | Tier 1 | rs11205354 | 1:150,249,101 | C/A | MRPS21†, RPRD2†, ECM1‡ | |
| KRTCAP2 | FEV1/FVC | Tier 1 | rs141942982 | 1: 155153537 | T/C | THBS4‡ | |
| RALGPS2 (intron) | FEV1 | FVC | Tier 1 | rs4651005 | 1:178,719,306 | C/T | ANGPTL1† |
| LMOD1 (intron) | FEV1/FVC | Tier 2 | rs4309038 | 1:201,884,647 | G/C | SHISA4† | |
| ATAD2B (intron) | FVC | FEV1 | Tier 2 | rs13009582 | 2:24,018,480 | G/A | UBXN2A† |
| PKDCC | FVC | FEV1 | Tier 1 | rs4952564 | 2:42,243,850 | A/G | PKDCC† |
| ITGAV (intron) | FEV1/FVC | Tier 1 | rs2084448 | 2:187,530,520 | C/T | ITGAV† | |
| SPATS2L (intron) | FEV1/FVC | Tier 2 | rs985256 | 2:201,208,692 | C/A | SPATS2L† | |
| C2orf54 | FVC | Tier 1 | rs6437219 | 2:241,844,033 | C/T | C2orf54†* | |
| MIR548G | FVC | FEV1 | Tier 1 | rs1610265 | 3:99,420,192 | T/C | FILIP1L† |
| BCHE (exon) | FEV1/FVC | Tier 1 | rs1799807 | 3:165,548,529 | C/T | BCHE* | |
| BTC (intron) | FEV1/FVC | FEV1 | Tier 1 | rs62316310 | 4:75,676,529 | G/A | BTC* |
| LOC100996325 | FEV1 | FEV1/FVC | Tier 1 | rs11739847 | 5:609,661 | A/G | CEP72* |
| RNU6–71P | FEV1 | FEV1/FVC, PEF | Tier 1 | rs2894837 | 6:56,336,406 | G/A | DST* |
| JAZF1 (intron) | FEV1 | FVC, PEF | Tier 1 | rs1513272 | 7:28,200,097 | C/T | JAZF1† |
| MET (intron) | FEV1/FVC | Tier 2 | rs193686 | 7:116,431,427 | T/C | MET† | |
| IER5L | FEV1 | Tier 2 | rs967497 | 9:131,943,843 | G/A | CRAT†, PPP2R4†, IER5L* | |
| DOCK9 | FEV1/FVC | Tier 1 | rs11620380 | 13:99,665,512 | A/C | DOCK9* | |
| CHAC1 | FVC | Tier 1 | rs4924525 | 15:41,255,396 | A/C | INO80†, CHP1†, RAD51† | |
| ATP2A3 | FEV1/FVC | Tier 1 | rs8082036 | 17:3,882,613 | G/C | ATP2A3† | |
| PITPNM3 | FEV1 | Tier 2 | rs4796334 | 17:6,469,793 | A/G | KIAA0753†*, TXNDC17†, PITPNM3† | |
| TNFSF12-TNFSF13 | FEV1 | Tier 2 | rs4968200 | 17:7,448,457 | C/G | TNFSF13†, SENP3† | |
| NCOR1 (intron) | FVC | Tier 2 | rs34351630 | 17:16,030,520 | C/T | ADORA2B†, TTC19† | |
| ASPSCR1 (intron) | FVC | FEV1 | Tier 1 | rs59606152 | 17:79,952,944 | C/T | LRRC45* |
| C18orf8 | FVC | FEV1 | Tier 1 | rs303752 | 18:21,074,255 | A/G | C18orf8† |
| ZFP82 | FVC | Tier 2 | rs2967516 | 19:36,881,643 | A/G | ZFP14†, ZFP82† | |
| MFAP2 | FEV1/FVC | FVC, PEF | Previous | rs9435733 | 1:17,308,254 | C/T | MFAP2† |
| LOC101929516 | FEV1/FVC | FEV1, PEF | Previous | rs755249 | 1:39,995,074 | T/C | PABPC4† |
| TGFB2 | PEF | Previous | rs6604614 | 1:218,631,452 | C/G | TGFB2† | |
| TRAF3IP1 | FEV1 | FEV1/FVC | Previous | rs6710301 | 2:239,441,308 | C/A | ASB1* |
| SLMAP (intron) | FEV1 | FVC, FEV1/FVC, PEF | Previous | rs6445932 | 3:57,879,611 | T/G | SLMAP† |
| RSRC1 (intron) | FVC | FEV1 | Previous | rs12634907 | 3:158,226,886 | G/A | RSRC1† |
| GSTCD (intron) | FEV1 | FVC, FEV1/FVC | Previous | rs11722225 | 4:106,766,430 | T/C | INTS12† |
| NPNT (intron) | FEV1/FVC | FEV1, FVC, PEF | Previous | rs34712979 | 4:106,819,053 | A/G | NPNT†‡ |
| AP3B1 (intron) | FVC | Previous | rs425102 | 5:77,396,400 | G/T | AP3B1† | |
| SPATA9 | FEV1/FVC | Previous | rs987068 | 5:95,025,146 | C/G | RHOBTB3† | |
| P4HA2-AS1 | FVC | Previous | rs3843503 | 5:131,466,629 | A/T | SLC22A5†, P4HA2†, C1QTNF5‡ | |
| CYFIP2 (intron) | FEV1/FVC | FEV1, PEF | Previous | rs11134766 | 5:156,908,317 | T/C | ADAM19† |
| ADAM19 (intron) | FEV1/FVC | FEV1, PEF | Previous | rs11134789 | 5:156,944,199 | A/C | ADAM19†* |
| DSP (intron) | FEV1/FVC | Previous | rs2076295 | 6:7,563,232 | T/G | DSP† | |
| MIR588 | FVC | FEV1 | Previous | rs6918725 | 6:126,990,392 | T/G | CENPW† |
| GPR126 (exon) | FEV1/FVC | FVC, PEF | Previous | rs17280293 | 6:142,688,969 | A/G | GPR126* |
| C1GALT1 (intron) | FEV1/FVC | Previous | rs4318980 | 7:7,256,490 | A/G | C1GALT1† | |
| QSOX2 (3’-UTR) | FVC | FEV1 | Previous | rs7024579 | 9:139,100,413 | T/C | QSOX2† |
| DNLZ (intron) | FVC | Previous | rs4073153 | 9:139,259,349 | G/A | SNAPC4†, CARD9†, INPP5E† | |
| CDC123 (intron) | FEV1/FVC | FEV1, FVC, PEF | Previous | rs7090277 | 10:12,278,021 | T/A | NUDT5† |
| MYPN (intron) | FVC | FEV1 | Previous | rs10998018 | 10:69,962,954 | A/G | MYPN* |
| EML3 (intron) | FEV1 | FVC | Previous | rs71490394 | 11:62,370,155 | G/A | EEF1G†, ROM1†*, EML3†* |
| ARHGEF17 (intron) | FEV1/FVC | FEV1 | Previous | rs2027761 | 11:73,036,179 | C/T | FAM168A†, ARHGEF17†* |
| RAB5B (intron) | FEV1 | Previous | rs1689510 | 12:56,396,768 | C/G | CDK2† | |
| LRP1 (intron) | FEV1/FVC | PEF | Previous | rs11172113 | 12:57,527,283 | T/C | LRP1† |
| FGD6 (intron) | FEV1/FVC | Previous | rs113745635 | 12:95,554,771 | T/C | FGD6† | |
| RPAP1 | FEV1/FVC | Previous | rs2012453 | 15:41,840,238 | G/A | ITPKA†, LTK†, TYRO3†, RPAP1† | |
| AAGAB | FVC | Previous | rs12917612 | 15:67,491,274 | A/C | AAGAB†, SMAD3†, IQCH† | |
| THSD4 (intron) | FEV1/FVC | FEV1, PEF | Previous | rs1441358 | 15:71,612,514 | G/T | THSD4† |
| IL27 | FEV1 | Previous | rs12446589 | 16:28,870,962 | A/G | SBK1†, TUFM†, CCDC101†, SULT1A1†, SULT1A2†*, SH2B1†, NPIPL1†, CLN3†, ATXN2L†, EIF3C† | |
| MMP15 (intron) | FEV1/FVC | Previous | rs11648508 | 16:58,063,513 | G/T | MMP15† | |
| SSH2 (intron) | FEV1/FVC | PEF | Previous | rs2244592 | 17:28,072,327 | A/G | EFCAB5† |
| FBXL20 (intron) | FVC | FEV1 | Previous | rs8069451 | 17:37,504,933 | C/T | CRKRS†, FBXL20† |
| MAPT-AS1 | FEV1 | FVC, PEF | Previous | rs79412431 | 17:43,940,021 | A/G | LRRC37A4†, MAPT* |
| TSEN54 (intron) | FEV1 | Previous | rs9892893 | 17:73,525,670 | G/T | CASKIN2†, TSEN54* | |
| LTBP4 (exon) | FEV1/FVC | PEF | Previous | rs34093919 | 19:41,117,300 | G/A | LTBP4* |
| ABHD12 (intron) | FEV1 | Previous | rs2236180 | 20:25,282,608 | C/T | PYGB†* | |
| UQCC1 (5’-UTR) | FVC | FEV1, PEF | Previous | rs143384 | 20:34,025,756 | G/A | UQCC1†, GDF5† |
| SLC2A4RG (intron) | FVC | FEV1 | Previous | rs4809221 | 20:62,372,706 | A/G | LIME1† |
| SCARF2 (intron) | FEV1 | FEV1/FVC | Previous | rs9610955 | 22:20,790,723 | C/G | SCARF2*‡ |
Genes implicated by eQTL signals: Lung eQTL (n=1,111) and Blood eQTL (n=4,896) datasets and eleven GTEx (V7) tissues were screened: Artery Aorta (n=267), Artery Coronary (n=152), Artery Tibial (n=388), Colon Sigmoid (n=203), Colon Transverse (n=246), Esophagus Gastroesophageal Junction (n=213), Esophagus Muscularis (n=335), Lung (n=383), Small Intestine Terminal Ileum (n=122), Stomach (n=237), and Whole Blood (n=369); see Supplementary Table 13 for direction of gene expression for the COPD risk (FEV1/FVC reducing) allele.
Genes implicated by pQTL signals: pQLT look up in 3,600 plasma proteins (n up to 3,300).
Genes implicated because they contain a deleterious variant (Supplementary Table 11).
“Other traits” column lists the other lung function traits for which the sentinel was associated at P<5×10−9 in the meta-analysis of UK Biobank and SpiroMeta.
In total, 107 putative causal genes were identified: 8 by both a deleterious variant and an eQTL signal (including KIAA0753 implicated by two deleterious variants), 1 (NPNT) by both an eQTL and a pQTL signal, 1 (SCARF2) by both a deleterious variant and a pQTL signal, 13 by a deleterious variant only, 81 by an eQTL signal only and 3 by a pQTL signal only