Background
Methods
Selection of asthma loci
Genomic coordinates and 1000 genomes project
Linkage disequilibrium analysis
Functional annotation
Results
Asthma loci
Linkage disequilibrium variants
Identification of deleterious and regulatory variants
LD Variant | Asthma Variant | LD r2 valuea | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
ID | Gene | Annotation | ID | Gene(s) | Annotation | AFR | AMR | EAS | EUR | SAS |
rs8084 |
HLA-DRA
| splice acceptor | rs3129890 |
HLA-DRA
| downstream | 0.889 | < 0.6 | 0.815 | < 0.6 | < 0.6 |
rs199503730 |
MICA
| frameshift | rs361525 |
TNF, LTA
| upstream | < 0.6 | < 0.6 | < 0.6 | < 0.6 | 0.726 |
rs67841474 |
MICA
| frameshift | rs2428494 |
HLA-B
| upstream | < 0.6 | < 0.6 | 0.671 | < 0.6 | < 0.6 |
rs15895 |
OAS2
| stop lost | rs1293767 |
OAS2
| missense | 0.749 | 0.609 | < 0.6 | < 0.6 | < 0.6 |
rs11078928 |
GSDMB
| splice acceptor | rs907092 |
IKZF3
| synonymous | < 0.6 | 0.889 | 0.845 | 0.892 | 0.966 |
rs4795397 |
IKZF3
| upstream | < 0.6 | 0.913 | 0.995 | 0.950 | 0.846 | |||
rs11655198 |
ZPBP2
| intron | < 0.6 | 0.804 | 0.995 | 0.832 | 0.898 | |||
rs2305480 |
GSDMB
| missense | 0.961 | 0.988 | 1 | 0.996 | 1 | |||
rs62067034 |
GSDMB
| intron | 0.707 | 0.871 | 1 | 0.849 | 0.917 | |||
rs11078927 |
GSDMB
| intron | 0.984 | 0.994 | 1 | 1 | 0.995 | |||
rs2290400 |
GSDMB
| upstream | < 0.6 | 0.726 | 0.945 | 0.811 | 0.704 | |||
rs7216389 |
GSDMB
| upstream | < 0.6 | 0.831 | 0.967 | 0.792 | 0.723 | |||
rs4794820 |
ORMDL3, LRRC3C
| downstream | < 0.6 | 0.688 | 0.899 | 0.731 | 0.678 | |||
rs12450323 |
IKZF3
| intron | < 0.6 | < 0.6 | 0.684 | < 0.6 | < 0.6 | |||
rs146576636 |
ADAM33
| frameshift | rs543749 |
ADAM33
| intron | < 0.6 | < 0.6 | 0.804 | < 0.6 | < 0.6 |
rs574174 |
ADAM33
| intron | < 0.6 | < 0.6 | 0.846 | < 0.6 | < 0.6 | |||
rs612709 |
ADAM33
| upstream | < 0.6 | < 0.6 | 0.800 | < 0.6 | < 0.6 |
LD Variants | Asthma Variants | ||
---|---|---|---|
ID | Gene | Annotation | ID(s) |
rs115676129 |
ABI3BP
| missensea, b | rs9823506 |
rs2275254 |
CHIA
| missensea, b | rs2282290 |
rs2305479 |
GSDMB
| missensea, b | rs2305480, rs62067034, rs11078927, rs7216389, rs907092, rs4795397, rs11655198, rs2290400, rs12450323, rs4794820 |
rs1129808 |
HLA-DQA1
| missensea, b | rs3104367, rs9272346, rs9273373 |
rs1142332 |
HLA-DQA1
| missensea, b | rs3104367, rs9272346, rs9273373 |
rs1049057 |
HLA-DQB1
| missensea, b | rs3104367, rs9272346, rs9273373 |
rs1140319 |
HLA-DQB1
| missensea, b | rs3104367, rs9272346, rs9273373 |
rs73022563 |
PLEKHG4B
| missensea, b | rs62344088 |
rs6482626 |
PTCHD3
| missensea, b | rs660498 |
rs2305089 |
TBXT
| missensea, b | rs6456042 |
rs41273547 |
ABI3BP
| missensea | rs9823506 |
rs148714608 |
CLSTN2
| missensea | rs77960860 |
rs1042308 |
HLA-DPA1
| missensea | rs987870 |
rs1071630 |
HLA-DQA1
| missensea | rs3104367, rs9272346, rs9273373 |
rs1129740 |
HLA-DQA1
| missensea | rs3104367, rs9272346, rs9273373 |
rs1142328 |
HLA-DQA1
| missensea | rs3104367, rs9272346, rs9273373 |
rs1142331 |
HLA-DQA1
| missensea | rs3104367, rs9272346, rs9273373 |
rs3208105 |
HLA-DQA1
| missensea | rs3104367, rs9272346, rs9273373 |
rs1049163 |
HLA-DQB1
| missensea | rs9273373 |
rs1130398 |
HLA-DQB1
| missensea | rs3104367, rs9272346, rs9273373 |
rs1140318 |
HLA-DQB1
| missensea | rs3104367, rs9272346, rs9273373 |
rs1140320 |
HLA-DQB1
| missensea | rs3104367, rs9272346, rs9273373 |
rs41558312 |
MICA
| missensea | rs361525 |
rs1801280 |
NAT2
| missensea | rs1799929, rs1208 |
rs2363468 |
PIKFYVE
| missensea | rs4673397 |
rs13436090 |
PLEKHG4B
| missensea | rs62344088 |
rs3777134 |
SPINK5
| missensea | rs2303064 |
rs682632 |
TEK
| missensea | rs72721168 |
rs1140404 |
HLA-B
| missenseb | rs1800629 |
rs41543121 |
HLA-B
| missenseb | rs1800629 |
rs41556417 |
HLA-B
| missenseb | rs361525 |
rs4193 |
HLA-DQA1
| missenseb | rs3104367, rs9272346, rs9273373 |
rs2233953 |
PSORS1C2
| missenseb | rs1800629 |
rs7686508 |
SEC31A
| missenseb | rs10022260 |
eQTL | Affected Gene(s) | Tissue | Affected Binding Motif(s) | Asthma Variant(s) in LD |
---|---|---|---|---|
rs14078 |
NPPA
| Lymphoblastoid | C/EBP | rs5065 |
rs17032120 |
UNC50
| Monocytes | Whn | rs2278206 |
rs3769737 |
UNC50
| Monocytes | Gm12892, Hsmm, Hsmmt, Huh7 | rs2278206 |
rs17446058 |
UNC50
| Monocytes | deltaEF1 | rs2278206 |
rs5743563 |
TLR10, TLR1, TLR6
| Lymphoblastoid | YY1 | rs4129009, rs4833095 |
rs5743565 |
TLR10, TLR6, TLR1
| Lymphoblastoid | GATA-4 | rs4129009, rs4833095 |
rs7941648 |
RPS6KB2
| Lymphoblastoid | CDP, BCL6, Foxd3, Sox7, Sox18, Sry, Sox5 | rs1695, rs6591255 |
rs12654778 |
ADRB2
| Lymphoblastoid | TP53 | rs1042713 |
rs10039559 |
RAD50
| Lymphoblastoid | C/EBP | rs11745587 |
rs204992 |
HLA-DQA1
| Lymphoblastoid | CAC-bindingprotein | rs204993 |
rs3131294 |
HLA-DQA1, HLA-C, HLA-DQB1, HLA-DRB1, HLA-DRB5, HLA-DRA, ERG
a
, HCG27, HLA-C, LIMS1
a
| Lymphoblastoid, Monocytes | AIRE | rs3135388 |
rs6928482 |
HLA-DQA1, HLA-DQA2
| Lymphoblastoid | Zfp410 | rs3104367, rs9272346, rs9273373 |
rs1063355 |
HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRA
| Lymphoblastoid | Isgf3g | rs3104367, rs9272346, rs9273373 |
rs2076523 |
HLA-DQA2, HLA-DQB1, HLA-DQA2
| Lymphoblastoid | Hepg2 | rs9268516 |
rs2213585 |
HLA-DQB1, HLA-DRB1, HLA-DRB5, HLA-DRA, HLA-DQA1
| Lymphoblastoid | Zfp410 | rs3129890 |
rs6906021 |
POLR2A, TAF1, PAX5
| Lymphoblastoid | Pit-1 | rs3104367, rs9272346, rs9273373 |
rs7970524 |
HAL, LTA4H
| Monocytes | AR | rs2540493 |
rs12429692 |
ALOX5AP
| Monocytes | PU.1 | rs10507391 |
rs3862469 |
DEXI, LOC642755
a
| Monocytes | NF-E2, ZBRK1, MAFB | rs9923856 |
rs11642631 |
DEXI, LOC642755
a
| Monocytes | VDR | rs9923856 |
rs12946510 |
KRT222P, MEd24, NR1D1, ORMDL3
| Lymphoblastoid | FOXO1, IRF1, Srf, Elf3 | rs907092, rs4795397, rs11655198, rs2305480, rs62067034, rs11078927, rs2290400, rs7216389, rs4794820, rs12450323 |
rs8076131 |
KRT222P, NR1D1, ORMDL3
| Lymphoblastoid | Tcfe2a | rs2305480, rs11078927, rs7216389, rs907092, rs4795397, rs11655198, rs62067034, rs2290400, rs4794820, rs12450323 |
rs11557466 |
ORMDL3
| Lymphoblastoid | HOXA5, REST, NRSE, HIF1 | rs2305480, rs62067034, rs11078927, rs907092, rs4795397, rs11655198, rs2290400, rs7216389, rs4794820, rs12450323 |
rs8069732 |
TBKBP1
| Monocytes | NF-E2, Fos, GCN4, hoxa9, Cdx-2, Hoxa11, Hoxc10, Hoxc11, Hoxc9, Hoxa9, Hoxb9 | rs5918 |