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. Author manuscript; available in PMC: 2018 Oct 9.
Published in final edited form as: Nat Genet. 2018 Apr 9;50(4):559–571. doi: 10.1038/s41588-018-0084-1

Table 1.

Summary of discovery and fine-mapping analyses of the 40 index coding variants associated with T2D (p<2.2×10−7).

Discovery meta-analysis using exome-array component: 81,412 T2D cases and 370,832 controls from diverse ancestries Fine-mapping meta-analysis using GWAS: 50,160 T2D cases and 465,272 controls from European ancestry
Locus Index variant rs ID Chr Pos Alleles RAF BMI unadjusted BMI adjusted RAF OR L95 U95 p-value Group
R/O OR L95 U95 p-value OR L95 U95 p-value
Previously reported T2D associated loci
MACF1 MACF1 p.Met1424Val rs2296172 1 39,835,817 G/A 0.193 1.06 1.05 1.08 6.7×10−16 1.04 1.03 1.06 5.9×10−8 0.22 1.08 1.06 1.1 1.6×10−15 3
GCKR GCKR p.Pro446Leu rs1260326 2 27,730,940 C/T 0.630 1.06 1.05 1.08 5.3×10−25 1.06 1.04 1.07 3.2×10−18 0.607 1.05 1.04 1.07 9.1×10−10 1
THADA THADA p.Cys845Tyr rs35720761 2 43,519,977 C/T 0.895 1.08 1.05 1.1 4.6×10−15 1.07 1.05 1.10 8.3×10−16 0.881 1.1 1.07 1.12 3.4×10−12 2
GRB14 COBLL1 p.Asn901Asp rs7607980 2 165,551,201 T/C 0.879 1.08 1.06 1.11 8.6×10−20 1.09 1.07 1.12 5.0×10−23 0.871 1.08 1.06 1.11 3.6×10−10 2
PPARG PPARG p.Pro12Ala rs1801282 3 12,393,125 C/G 0.887 1.09 1.07 1.11 1.4×10−17 1.10 1.07 1.12 2.7×10−19 0.876 1.12 1.09 1.14 3.7×10−17 3
IGF2BP2 SENP2 p.Thr291Lys rs6762208 3 185,331,165 A/C 0.367 1.03 1.01 1.04 1.6×10−6 1.03 1.02 1.05 3.0×10−8 0.339 1.02 1.01 1.04 0.01 2
WFS1 WFS1 p.Val333Ile rs1801212 4 6,302,519 A/G 0.748 1.07 1.06 1.09 1.1×10−24 1.07 1.05 1.08 7.1×10−21 0.703 1.07 1.05 1.09 4.1×10−13 2
PAM-PPIP5K2 PAM p.Asp336Gly rs35658696 5 102,338,811 G/A 0.045 1.13 1.10 1.17 1.2×10−16 1.13 1.09 1.17 7.4×10−15 0.051 1.17 1.13 1.22 2.5×10−17 1
RREB1 RREB1 p.Asp1171Asn rs9379084 6 7,231,843 G/A 0.884 1.08 1.06 1.11 1.1×10−13 1.10 1.07 1.13 1.5×10−17 0.888 1.09 1.06 1.12 1.1×10−9 1
RREB1 p.Ser1499Tyr rs35742417 6 7,247,344 C/A 0.836 1.04 1.03 1.06 5.5×10−8 1.04 1.02 1.06 2.2×10−7 0.817 1.04 1.02 1.07 0.00012 2
MHC TCF19 p.Met131Val rs2073721 6 31,129,616 G/A 0.749 1.04 1.02 1.05 1.6×10−10 1.04 1.02 1.05 2.3×10−9 N/A N/A N/A N/A N/A N/A
PAX4 PAX4 p.Arg190His rs2233580 7 127,253,550 T/C 0.029 1.36 1.25 1.48 1.8×10−12 1.38 1.26 1.51 4.2×10−13 0 N/A N/A N/A N/A N/A
SLC30A8 SLC30A8 p.Arg276Trp rs13266634 8 118,184,783 C/T 0.691 1.09 1.08 1.11 1.9×10−47 1.09 1.08 1.11 1.3×10−47 0.683 1.12 1.1 1.14 8.2×10−36 1
GPSM1 GPSM1 p.Ser391Leu rs60980157 9 139,235,415 C/T 0.771 1.06 1.05 1.08 3.2×10−16 1.06 1.05 1.08 6.6×10−16 0.756 1.06 1.04 1.09 8.3×10−8 3
KCNJ11-ABCC8 KCNJ11 p.Lys29Glu rs5219 11 17,409,572 T/C 0.364 1.06 1.05 1.07 5.7×10−22 1.07 1.05 1.08 1.5×10−22 0.381 1.07 1.05 1.09 8.1×10−16 1
CENTD2 ARAP1 p.Gln802Glu rs56200889 11 72,408,055 G/C 0.733 1.04 1.02 1.05 4.8×10−8 1.05 1.03 1.06 5.2×10−10 0.727 1.05 1.03 1.07 2.3×10−8 2
KLHDC5 MRPS35 p.Gly43Arg rs1127787 12 27,867,727 G/A 0.850 1.06 1.04 1.08 1.4×10−11 1.05 1.03 1.07 1.5×10−8 0.842 1.06 1.04 1.09 2.2×10−7 2
HNF1A HNF1A p.Ile75Leu rs1169288 12 121,416,650 C/A 0.323 1.04 1.03 1.06 1.1×10−11 1.04 1.02 1.06 1.9×10−10 0.33 1.05 1.04 1.07 4.6×10−9 1
HNF1A p.Ala146Val rs1800574 12 121,416,864 T/C 0.029 1.11 1.06 1.15 6.1×10−8 1.10 1.06 1.15 1.3×10−7 0.03 1.16 1.1 1.21 5.0×10−9 1
MPHOSPH9 SBNO1 p.Ser729Asn rs1060105 12 123,806,219 C/T 0.815 1.04 1.02 1.06 5.7×10−7 1.04 1.02 1.06 1.1×10−7 0.787 1.04 1.02 1.06 3.6×10−5 2
CILP2 TM6SF2 p.Glu167Lys rs58542926 19 19,379,549 T/C 0.076 1.07 1.05 1.10 4.8×10−12 1.09 1.06 1.11 3.4×10−15 0.076 1.09 1.05 1.12 2.0×10−7 1
GIPR GIPR p.Glu318Gln rs1800437 19 46,181,392 C/G 0.200 1.03 1.02 1.05 7.1×10−5 1.06 1.04 1.07 6.8×10−12 0.213 1.09 1.06 1.12 4.6×10−9 1
HNF4A HNF4A p.Thr139Ile rs1800961 20 43,042,364 T/C 0.032 1.09 1.05 1.13 2.6×10−8 1.10 1.06 1.14 5.0×10−8 0.037 1.17 1.12 1.22 1.4×10−12 1
MTMR3-ASCC2 ASCC2 p.Asp407His rs28265 22 30,200,761 C/G 0.925 1.09 1.06 1.11 2.1×10−12 1.09 1.07 1.12 4.4×10−14 0.916 1.1 1.07 1.14 9.6×10−11 3
Novel T2D associated loci
FAM63A FAM63A p.Tyr95Asn rs140386498 1 150,972,959 A/T 0.988 1.21 1.14 1.28 7.5×10−8 1.19 1.12 1.26 6.7×10−7 0.986 1.15 1.06 1.25 0.00047 3
CEP68 CEP68 p.Gly74Ser rs7572857 2 65,296,798 G/A 0.846 1.05 1.04 1.07 8.3×10−9 1.05 1.03 1.07 6.6×10−7 0.830 1.06 1.03 1.08 6.6×10−7 2
KIF9 KIF9 p.Arg638Trp rs2276853 3 47,282,303 A/G 0.588 1.02 1.01 1.04 8.0×10−5 1.03 1.02 1.05 5.3×10−8 0.602 1.04 1.02 1.05 2.6×10−5 3
ANKH ANKH p.Arg187Gln rs146886108 5 14,751,305 C/T 0.996 1.29 1.16 1.45 1.4×10−7 1.27 1.13 1.41 3.5×10−7 0.995 1.51 1.29 1.77 3.5×10−7 1
POC5 POC5 p.His36Arg rs2307111 5 75,003,678 T/C 0.562 1.05 1.04 1.07 1.6×10−15 1.03 1.01 1.04 2.1×10−5 0.606 1.06 1.05 1.08 1.1×10−12 1
LPL LPL p.Ser474* rs328 8 19,819,724 C/G 0.903 1.05 1.03 1.08 6.8×10−9 1.05 1.03 1.07 2.3×10−7 0.901 1.08 1.05 1.11 7.1×10−8 1
PLCB3† PLCB3 p.Ser778Leu rs35169799 11 64,031,241 T/C 0.071 1.05 1.02 1.08 1.3×10−5 1.06 1.03 1.09 1.8×10−7 0.065 1.07 1.04 1.11 3.8×10−5 1
TPCN2 TPCN2 p.Val219Ile rs72928978 11 68,831,364 G/A 0.890 1.05 1.02 1.07 5.2×10−7 1.05 1.03 1.07 1.8×10−8 0.847 1.03 1.00 1.05 0.042 2
WSCD2 WSCD2 p.Thr113Ile rs3764002 12 108,618,630 C/T 0.719 1.03 1.02 1.05 3.3×10−8 1.03 1.02 1.05 1.2×10−7 0.736 1.05 1.03 1.07 8.1×10−7 1
ZZEF1 ZZEF1 p.Ile402Val rs781831 17 3,947,644 C/T 0.422 1.04 1.03 1.05 8.3×10−11 1.03 1.02 1.05 1.8×10−7 0.407 1.04 1.02 1.05 2.1×10−5 2
MLX MLX p.Gln139Arg rs665268 17 40,722,029 G/A 0.294 1.04 1.02 1.05 2.0×10−8 1.03 1.02 1.04 1.1×10−5 0.280 1.04 1.02 1.06 5.2×10−6 2
TTLL6 TTLL6 p.Glu712Asp rs2032844 17 46,847,364 C/A 0.754 1.04 1.02 1.06 1.2×10−7 1.03 1.01 1.04 0.00098 0.750 1.04 1.02 1.06 9.5×10−5 3
C17orf58† C17orf58 p.Ile92Val rs9891146 17 65,988,049 T/C 0.277 1.04 1.02 1.06 1.3×10−7 1.02 1.00 1.04 0.00058 0.269 1.05 1.03 1.07 1.7×10−7 2
ZHX3† ZHX3 p.Asn310Ser rs17265513 20 39,832,628 C/T 0.211 1.05 1.03 1.07 9.2×10−8 1.04 1.02 1.05 2.9×10−6 0.208 1.02 1.00 1.04 0.068 N/A
PNPLA3 PNPLA3 p.Ile148Met rs738409 22 44,324,727 G/C 0.239 1.04 1.03 1.05 2.1×10−10 1.05 1.03 1.06 2.8×10−11 0.230 1.05 1.03 1.07 5.8×10−6 1
PIM3 PIM3 p.Val300Ala rs4077129 22 50,356,693 T/C 0.276 1.04 1.02 1.05 1.9×10−7 1.04 1.02 1.06 3.5×10−8 0.280 1.04 1.02 1.06 8.7×10−5 3

Chr: chromosome. Pos: Position build 37. RAF: risk allele frequency. R: risk allele. O: other allele. BMI: body mass index. OR: odds ratio. L95: lower 95% confidence interval. U95: upper 95% confidence interval. GWAS: genome wide association studies.

†

Summary statistics from European ancestry specific meta-analyses of 48,286 cases and 250,671 controls. Fine-mapping group 1: signal is driven by coding variant, group 2: signal attributable to non-coding variants, and group 3: consistent with partial role for coding variants. p-values are based on the meta-analyses of discovery stage and fine-mapping studies as appropriate.