Table 5. Previously published ALT level/NAFLD risk-associated variants with genome-wide significance and associations with advanced fibrosis/cirrhosis and platelet count at enrollment among patients with NAFLD (n = 60,542).
| FIB4 score >2.670 (n = 7,376 cases, 53,166 controls) | NAFLD fibrosis score ≥0.676 (n = 18,363 cases, 42,179 controls) | Platelet Count (n = 60,542) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GENE | rsID | Chr | Pos | EA | EAF | OR (95% CI) | P | OR (95% CI) | P | BETA | SE | P |
| LYPLAL1 | rs12137855 | 1 | 219448378 | C | 0.8 | 0.97 (0.94–1.01) | 0.11 | 0.98 (0.95–1.01) | 0.18 | 0.214 | 0.214 | 0.32 |
| LYPLAL1 | rs3001032 | 1 | 219727779 | T | 0.69 | 1.00 (0.97–1.03) | 0.91 | 0.98 (0.95–1.00) | 0.082 | -0.298 | 0.178 | 0.095 |
| *GCKR | rs780094 | 2 | 27741237 | T | 0.4 | 1.04 (1.01–1.07) | 0.0092 | 1.00 (0.97–1.02) | 0.8 | 1.605 | 0.179 | 2.5E-19 |
| HSD17B13 | rs6834314 | 4 | 88213808 | A | 0.72 | 1.05 (1.02–1.08) | 0.0023 | 1.01 (0.98–1.04) | 0.47 | -1.504 | 0.193 | 6.1E-15 |
| *HSD17B13 | rs72613567 | 4 | 88231392 | T | 0.73 | 1.06 (1.02–1.09) | 9.7E-04 | 1.02 (0.99–1.05) | 0.25 | -1.688 | 0.206 | 2.2E-16 |
| TRIB1 | rs2954021 | 8 | 126482077 | A | 0.5 | 0.99 (0.97–1.02) | 0.55 | 0.99 (0.96–1.01) | 0.25 | -0.259 | 0.169 | 0.13 |
| PPP1R3B | rs4240624 | 8 | 9184231 | G | 0.09 | 0.96 (0.92–1.01) | 0.084 | 1.00 (0.96–1.04) | 0.89 | -0.376 | 0.266 | 0.16 |
| ERLIN | rs10883437 | 10 | 101795361 | T | 0.61 | 1.02 (1.00–1.05) | 0.089 | 1.01 (0.99–1.04) | 0.4 | -0.183 | 0.171 | 0.29 |
| *ERLIN | rs11597390 | 10 | 101861435 | G | 0.64 | 1.01 (0.98–1.04) | 0.68 | 1.00 (0.97–1.02) | 0.72 | 0.164 | 0.18 | 0.36 |
| *ERLIN | rs11597086 | 10 | 101953705 | A | 0.58 | 1.01 (0.98–1.03) | 0.73 | 1.00 (0.97–1.03) | 0.95 | -0.068 | 0.184 | 0.71 |
| *ERLIN | rs11591741 | 10 | 101976501 | G | 0.58 | 1.00 (0.97–1.03) | 0.82 | 1.00 (0.97–1.02) | 0.87 | -0.064 | 0.182 | 0.72 |
| TM6SF2 | rs2228603 | 19 | 19329924 | T | 0.08 | 0.97 (0.92–1.03) | 0.32 | 0.97 (0.93–1.02) | 0.24 | 0.154 | 0.357 | 0.67 |
| *TM6SF2 | rs58542926 | 19 | 19379549 | T | 0.07 | 1.01 (0.96–1.06) | 0.64 | 0.97 (0.93–1.01) | 0.18 | -0.041 | 0.341 | 0.9 |
| *PNPLA3 | rs738409 | 22 | 44324727 | G | 0.23 | 1.08 (1.05–1.12) | 2.4E-07 | 1.06 (1.03–1.09) | 2.0E-05 | -2.88 | 0.204 | 3.9E-45 |
| PNPLA3 | rs2281135 | 22 | 44332570 | A | 0.17 | 1.08 (1.04–1.11) | 1.4E-05 | 1.05 (1.02–1.09) | 0.0007 | -2.382 | 0.221 | 5.1E-27 |
| PNPLA3 | rs2143571 | 22 | 44391686 | A | 0.18 | 1.05 (1.02–1.09) | 0.0013 | 1.04 (1.01–1.07) | 0.0042 | -1.437 | 0.206 | 2.8E-12 |
Abbreviations: rsID: dbSNP identifier (build 151), Chr: chromosome, Pos (Mb): megabase position on human genome reference hg19, EA: effect allele, EAF: effect allele frequency among Europeans (Million Veteran Program), OR: odds ratio, increased risk in cases compared to controls per effect allele (additive model), CI: confidence interval, Beta: effect size estimated increase in trait per increase copy of the effect allele (additive model). SE: Standard error on Beta, LYPLAL1: Lysophospholipase-like Protein 1, GCKR: glucokinase regulatory protein, HSD17B13: Hydroxysteroid 17-Beta Dehydrogenase 13, PPP1R3B: protein phosphatase 1, TM6SF2: Transmembrane 6 Superfamily Member 2, PNPLA3: patatin-like phospholipase domain-containing protein 3. All analysis adjusted for age, gender, and 10 principal components (PCs); adjustments including alcohol consumption are presented in the Supplement (S6a–S6c Table in S1 File). P-values below 0.006 (adjusted for multiple comparisons) are shown in bold font.