Table 3.
Single nucleotide polymorphisms associated with non-alcoholic fatty liver disease in genome wide association studies
| Region | SNPs | Reported gene(s) | Mapped gene | OR | Risk allele frequency in controls | P value | Gene product function | Context | Initial sample size | Replication sample size | Platform (SNPs passing QC) | Ref. |
| 22q13.3 | rs738409 (I148M), rs2896019-G | PNPLA3 | PNPLA3 | 2.02 | 0.450 | 2 × 10-20 | Adiponutrin (PNPLA3)–nutritionally regulated lysophosphatidic acyltransferase: expressed in liver and adipose tissue. High CH diet increases expression. Has TAG hydrolase and DG transacylase activity. Strong predictor of steatosis, inflammation and fibrosis. Dysfunctional PNPLA3 promotes accumulation of lipotoxic substrates. I148M–association with HCC in severely obese individuals | Intron | 392 Japanese cases, 934 Japanese controls | 172 Japanese cases, 1012 Japanese control | Illumina [261540] | [119,120] |
| rs738491, rs3761472, rs2143571 | SAMM50 | SAMM50 | ||||||||||
| rs6006473, rs5764455, rs6006611 | PARVB | PARVB | ||||||||||
| 1p35 | rs6691847-C | PTPRU | PTPRU - MATN1 | 1.32 | 0.770 | 7 × 10-6 | Member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate cell growth, differentiation, mitotic cycle, and oncogenic transformation | |||||
| 4q13.3 | rs222054-C | GC | LDHAL6EP - GC | 2.54 | 0.301 | 1 × 10-6 | Albumin gene family. Multifunctional protein found in plasma, ascitic fluid, cerebrospinal fluid and on the surface of many cell types. It binds to vitamin D and its plasma metabolites and transports them to target tissues | 126 European adolescent cases - 802 European adolescent controls | NR | Illumina [2078805] (imputed) | [142] | |
| 16q23 | rs11864146-A | SLC38, A8 | SLC38A8 | 3.14 | 0.100 | 2 × 10-6 | Amino acid transport: Putative sodium-coupled neutral amino acid transporter 8 | Intron | ||||
| 13q14.1 | rs7324845-A | LCP1 | LCP1 | 3.29 | 0.096 | 3 × 10-6 | L-plastin, an actin binding protein expressed in hemopoetic cell lineages. It is expressed by many solid tumor types of non-hemopoetic origin, suggesting its role in tumorigenesis | Intron | ||||
| 1p21 | rs12743824-C | LPPR4 | LPPR4 - PALMD | 2.30 | 0.441 | 5 × 10-6 | LPPR4: a lipid phosphate phosphatase, catalyzes the dephosphorylation of a number of bioactive lipid mediators, found to be important for axonal outgrowth; PALMD: cytosolic isoform of paralemmin-1, a lipid raft-associated protein implicated in cell shape control | NR | PALMD gene product - [143] | |||
| 7p14 | rs343064-A | Intergenic | TBX20-HERPUD2 | 1.31 | 0.400 | 3 × 10-8 | TBX20: transcription factor; HERPUD2: not reported | 236 non-Hispanic Caucasian women | NR | Illumina [324623] | SNPs of other genes were also associated with qulatitative traits (e.g. NAFLD activity score and FDFT1 - rs2645424) as discussed in the text [123] | |
| 2q31 | rs1529093-A | Intergenic | RPL29P8 - KRT8P40 | 4.13 | 0.410 | 2 × 10-6 | RPL29P8, KRT8P40: pseudogenes | NR | Illumina [324623] | |||
| 4p15.2 | rs959903-A | 23231 | SEL1L3 | 3.81 | 0.290 | 7 × 10-6 | Intron | NR | Illumina [324623] |
Not all GWAS studies were replicated. Risk gene variants with OR higher than 1.31 are indicated in the table. Based on the National Human Genome Research. SNPs: Single nucleotide polymorphisms; NR: Not reported.