Table 2.
New signals for glycemic traits discovered through UK Biobank (UKBB) (European ancestry only) GWAS in other RG models, UKBB (European ancestry only) GWAS on rare variants and cross-ancestry meta-analysis of up to 476,326 individuals of European or other ancestries (Black, Indian, Pakistani and Chinese) in UKBB
| Signal | Nearest gene(s) | Variants | Chr | Position | Type/model | Alleles | EAF | Effect | SE | P value | P het | n |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| UKBB | PEX7 | rs7756291 | 6 | 13,7235,325 | lead/6 | C/T | 0.45 | 0.0018 | 0.00030 | 3.0 × 10−9 | – | 379,291 |
| UKBB | INAFM2 | rs882829 | 15 | 40,607,689 | lead/2 | C/G | 0.92 | 0.0032 | 0.00057 | 1.6 × 10−8 | – | 379,301 |
| UKBB | INAFM2, C15orf52 | rs4143838 | 15 | 40,622,374 | lead/3 | T/C | 0.95 | −0.0039 | 0.00070 | 1.8 × 10−8 | – | 379,947 |
| UKBB | ADCY9, SRL | rs2018506 | 16 | 4,227,922 | lead/6 | C/G | 0.85 | −0.0023 | 0.00042 | 2.2 × 10−8 | – | 379,291 |
| UKBB | ERN1 | rs58642235 | 17 | 62,202,689 | lead/5 | T/C | 0.86 | −0.0024 | 0.00044 | 4.5 × 10−8 | – | 380,422 |
| UKBBa | WIPI1 | rs883541 | 17 | 66,449,122 | In LD with lead/6 | G/A | 0.23 | 0.0023 | 0.00036 | 5.5 × 10−11 | – | 380,422 |
| UKBBb | RFX1 | rs2305780 | 19 | 14,083,761 | lead/4 | T/C | 0.54 | 0.0016 | 0.00029 | 1.5 × 10−8 | – | 378,819 |
| UKBB, rarea | ANKH | rs146886108 | 5 | 14,751,305 | rare/1 | T/C | 0.0072 | −0.012 | 0.0018 | 3.2 × 10−12 | – | 380,432 |
| Cross-anc | RRNAD1 | rs3806415 | 1 | 156,698,265 | lead/5 | T/C | 0.32 | −0.0017 | 0.00031 | 3.6 × 10−8 | 0.51 | 476,326 |
| Sex-dim (w) | SGIP1 | rs7544505 | 1 | 66,998,618 | lead/5 | T/C | 0.84 | −0.0030 | 0.00053 | 1.8 × 10−8 | 0.019 | 207,903 |
| Sex-dim (m) | SGIP1 | rs7544505 | 1 | 66,998,618 | lead/5 | T/C | 0.84 | −0.0010 | 0.00063 | 0.10 | 172,529 | |
| Sex-dim (w) | POP7, EPO | rs534043 | 7 | 100,312,724 | lead/5 | A/G | 0.11 | −0.0018 | 0.00061 | 0.0029 | 0.0040 | 207,903 |
| Sex-dim (m) | POP7, EPO | rs534043 | 7 | 100,312,724 | lead/5 | A/G | 0.11 | −0.0046 | 0.00073 | 4.8 × 10−10 | 172,529 | |
| Sex-dim (w) | SLC43A2 | rs56405641 | 17 | 1,528,464 | lead/5 | C/T | 0.91 | −0.0040 | 0.00067 | 2.0 × 10−9 | 1.4 × 10−4 | 207,903 |
| Sex-dim (m) | SLC43A2 | rs56405641 | 17 | 1,528,464 | lead/5 | C/T | 0.91 | −4.1 × 10−5 | 0.00081 | 0.96 | 172,529 |
Loci showing sex-dimorphic effects on glycemic trait levels for the first time are also shown.
A signal was annotated as ‘UKBB’ if it reached genome-wide significance (P < 5.0 × 10−8) in UKBB (European ancestry) in any of the six RG models. A signal was annotated as ‘UKBB, rare’ if it reached genome-wide significance (P < 5.0 × 10−8) in UKBB (European ancestry) analysis for rare variants. Additional distinct signals with a region-wide threshold of P ≤ 1.0 × 10−5 are also reported. Effects and P values reported are from the model indicated in column ‘type/model’ (2, ASB20; 3, AS11; 4, ASB11; 5, AST20; 6, ASTB20). Heterogeneity among studies was assessed using the I2 index. P het values for the sex-dimorphic variants are from Cochran’s Q test (for sex heterogeneity representing the differences in allelic effects between sexes). Sex-dimorphic P values (2 degrees of freedom test of association assuming different effect sizes between the sexes) for the SGIP1, POP7/EPO and SLC43A2 variants were 3.2 × 10−8, 4.3 × 10−11 and 1.5 × 10−8, respectively.
aNonsynonymous variants.
bSynonymous variants.
Cross-anc, cross-ancestry; Sex-dim (m), sex-dimorphic results for men; Sex-dim (w), sex-dimorphic results for women.