Table 1.
GWAS the final trans-ethnic meta-analysis for keratoconus including all available cohorts, in 4669 cases and 116,547 controls.
| Region | Cytoband | Chr. | Coordinates | SNP | A1 | A2 | log(OR) | log(OR) SE | P-value | Genes within the region |
|---|---|---|---|---|---|---|---|---|---|---|
| 1* | 1q24.2 | 1 | 169018902..169073504 | rs1200108 | A | G | −0.163 | 0.026 | 4.52E−10 | ATP1B1 |
| 2* | 1q25.1 | 1 | 174990905..175010262 | rs6669560 | T | C | 0.156 | 0.026 | 2.92E−09 | MRPS14 |
| 3* | 1p22.2 | 1 | 207981419..208022291 | rs761276 | A | G | −0.137 | 0.024 | 8.02E−09 | CD34,CD46 |
| 4* | 2q22.1 | 2 | 141867420..141878395 | rs116792882 | T | C | −0.686 | 0.110 | 4.82E−10 | LRP1B |
| 5 | 3q26.31 | 3 | 171565463..172000456 | rs4894414 | T | C | 0.304 | 0.029 | 1.21E−26 | FNDC3B,TMEM212 |
| 6 | 5q11.2 | 5 | 52424518..52631507 | rs12515400 | T | C | 0.217 | 0.025 | 3.16E−18 | FST,ITGA2,MOCS2 |
| 7 | 5q23.2 | 5 | 121269498..121426675 | rs840464 | T | G | 0.233 | 0.025 | 1.72E−20 | SRFBP1,LOX |
| 8* | 6p12.3 | 6 | 50788778..51623864 | rs6904450 | A | T | −0.189 | 0.029 | 6.44E−11 | TFAP2B,PKHD1 |
| 9 | 6q13 | 6 | 75746765..75834971 | rs35523808 | A | T | 0.662 | 0.064 | 2.90E−25 | COL12A1 |
| 10 | 8q22.1 | 8 | 95832448..95992020 | rs1453379 | T | C | 0.156 | 0.025 | 3.32E−10 | TP53INP1,CCNE2,INTS8,NDUFAF6 |
| 11 | 9p23 | 9 | 13533300..13596674 | rs1324175 | T | C | −0.244 | 0.027 | 2.59E−19 | No Gene |
| 12 | 9q31.3 | 9 | 111372592..111500353 | rs2417930 | T | C | 0.162 | 0.024 | 2.62E−11 | ACTL7B |
| 13 | 9q34.3 | 9 | 137412655..137566891 | rs3118518 | A | G | 0.270 | 0.024 | 1.83E−28 | COL5A1,RXRA |
| 14 | 9q34.3 | 9 | 139830733..139866247 | rs11145948 | A | G | 0.173 | 0.025 | 9.89E−12 | FBXW5,PTGDS,C8G,LCN12 |
| 15* | 10q21.1 | 10 | 55196113..55196113 | rs117905623 | T | C | −0.381 | 0.068 | 1.89E−08 | No Gene |
| 16* | 10q26.11 | 10 | 120765171..120877372 | rs658352 | T | C | 0.176 | 0.025 | 3.71E−12 | NANOS1,FAM45B,EIF3A |
| 17 | 11p15.5 | 11 | 721570..825777 | rs7117921 | T | C | 0.265 | 0.025 | 1.09E−26 | CEND1,TALDO1,EPS8L2,PDDC1,PIDD, PNPLA2,RPLP2,SLC25A22 |
| 18* | 11q21 | 11 | 95308854..95308854 | rs11021221 | A | T | 0.204 | 0.034 | 1.49E−09 | FAM76B |
| 19* | 12p13.1 | 12 | 14288423..14290517 | rs17340879 | T | C | −0.493 | 0.082 | 1.77E−09 | GRIN2B |
| 20* | 12q13.13 | 12 | 51754629..51756269 | rs3782473 | T | C | 0.172 | 0.028 | 6.60E−10 | GALNT6 |
| 21 | 13q14.11 | 13 | 41049191..41950539 | rs2721051 | T | C | 0.452 | 0.037 | 5.71E-35 | MRPS31,MTRF1,NAA16,SLC25A15,ELF1, FOXO1, WBP4 |
| 22* | 13q22.1 | 13 | 73634051..73649152 | rs17285550 | A | G | −0.181 | 0.026 | 2.84E−12 | KLF5 |
| 23 | 15q21.2 | 15 | 51153797..51375011 | rs11634895 | A | G | −0.146 | 0.024 | 7.88E−10 | AP4E1,TNFAIP8L3 |
| 24* | 15q22.2 | 15 | 61038143..61038143 | rs76194223 | T | C | 0.258 | 0.046 | 1.75E−08 | RORA |
| 25 | 15q22.33 | 15 | 67438586..67694780 | rs12912010 | T | G | −0.312 | 0.029 | 1.99E−26 | AAGAB,IQCH,SMAD3 |
| 26 | 16q24.2 | 16 | 88274115..88344517 | rs11117401 | A | G | 0.236 | 0.026 | 3.68E−20 | BANP,ZNF469 |
| 27* | 17p13.2 | 17 | 4824625..4997433 | rs12603055 | C | G | −0.234 | 0.031 | 2.23E-14 | CHRNE,GP1BA,ZFP3,CAMTA2,ENO3,INCA1, KIF1C, PFN1,RNF167,SLC52A1,SPAG7 |
| 28* | 17p11.2 | 17 | 19619441..19653310 | rs4646785 | T | C | −0.197 | 0.029 | 9.01E−12 | ALDH3A1,SLC47A2 |
| 29* | 17q11.2 | 17 | 29883190..29889952 | rs56161228 | A | G | −0.210 | 0.033 | 2.70E−10 | RAB11FIP4 |
| 30* | 17q21.32 | 17 | 46328667..46645394 | rs12948086 | T | C | 0.165 | 0.028 | 5.33E−09 | HOXB1,HOXB2,HOXB3,SKAP1 |
| 31* | 17q21.33 | 17 | 48244531..48269903 | rs2075556 | C | G | −0.191 | 0.032 | 3.35E−09 | COL1A1,SGCA |
| 32* | 20p13 | 20 | 2076016..2143379 | rs6106210 | T | C | 0.172 | 0.026 | 2.85E−11 | STK35 |
| 33* | 20q13.31 | 21 | 25357226..25357226 | rs76747345 | A | G | −0.545 | 0.080 | 6.53E−12 | NA |
| 34* | 21q21.3 | 21 | 29521741..29623259 | rs2143683 | T | C | 0.185 | 0.027 | 3.51E−12 | No Gene |
| 35* | 21q22.3 | 21 | 47154348..47420667 | rs142493024 | A | G | 0.760 | 0.111 | 9.07E−12 | COL6A1,PCBP3 |
| 36* | 22q11.21 | 22 | 21322888..21323369 | rs756878 | T | C | 0.159 | 0.027 | 4.01E−09 | AIFM3 |
The field SNP lists the polymorphic variant showing the strongest association (P-value) for each region, for which the Chromosome number (Chr) and Coordinates (start and end coordinates in Human GHRC37/hg19) as well as the cytoband are shown. A1 lists the alleles at each SNP locus for which the effect sizes (as Odds Ratios, OR) and standard errors of estimates (log(OR) SE) are reported. Only coding genes nearest (<250 kb) to any significantly associated SNP are shown.
* Loci located within 1 million bp from loci previously associated at a GWAS level of significance (p < 5e−08) with keratoconus or CCT.
Bold characters indicate genes nearest to the SNP with the most significant association.