Table 4.
Association of NAFLD‐variants with type 2 diabetes in published GWAS
| Gene | SNP | Effect allele | other allele | T2D OR | 95% c.i. | P value | N | Data source |
|---|---|---|---|---|---|---|---|---|
| PNPLA3 | rs738409 | G (minor) | C | 1.04 | 1.01–1.07 | 0.0045 | 100 323 | diagram.mega‐meta |
| TM6SF2 | rs58542926 | T (minor) | C | 1.14 | 1.10–1.19 | 3.2 × 10−10 | 92 794 | Fuchsberger 2016 30 |
| MBOAT7 | rs641738 | T (minor) | C | 1.02 | 0.99–1.05 | 0.19 | 76 306 | diagram.mega‐meta |
| GCKR | rs1260326 | C (major)a | T | 1.06 | 1.03–1.09 | 3.4 × 10−5 | 100 584 | diagram.mega‐meta |
Data were downloaded from http://diagram-consortium.org/downloads.html or extracted from Fuchsberger et al. 30. aThe effect allele in GCKR is the major allele, encoding GCKR 446P. The 446P‐allele causes a relative gain‐of‐function compared to the L‐allele, leading to less hepatic phosphorylation of glucose, increased blood glucose and thus an increased risk of type 2 diabetes (T2D). Due to these strong pleiotropic effects of GCKR on glucose metabolism, it is problematic to use this variant as a proxy for NAFLD in Mendelian randomization analyses with T2D as an outcome.