Table 2.
Summary of top variants in the MLXIPL gene cluster exhibiting genome-wide significance for the TyG index, a marker of insulin resistance, identified within the Taiwan Biobank cohort
| GENE | CHR | Interval (b38) | Top SNP | Pos (b38) | Top P | Novel | TWAS | GWAS catalog |
|---|---|---|---|---|---|---|---|---|
| POM121 | 7 | 72879357..72951459 | rs117135057 | 72,938,316 | 1.8E-08 | yes | NA | TG, BMI |
| NSUN5 | 7 | 73302516..73308826 | rs3750074 | 73,308,628 | 1.1E-17 | yes | NA | NA |
| FKBP6a | 7 | 73328161..73358625 | rs186391487 | 73,384,030 | 9.2E-18 | yes | 1, 2 | TG |
| FZD9 | 7 | 73433778..73436120 | rs1178947 | 73,435,848 | 5.8E-69 | yes | 9 | TG, HDL-C |
| BAZ1B | 7 | 73440406..73522293 | rs111837003 | 73,493,129 | 1.2E-71 | yes | 1, 4, 6, 10, 11 | TG, HDL-C |
| BCL7B | 7 | 73536356..73557690 | rs13244614 | 73,559,524 | 9.0E-84 | yes | 1, 2, 8, 9 | HDL-C |
| TBL2 | 7 | 73567537..73578579 | rs13246490 | 73,578,020 | 2.6E-84 | yes | NA | TG, HDL-C, BMI |
| MLXIPL | 7 | 73593202..73647907 | rs3812316 | 73,606,007 | 8.5E-105 | no | 1, 2, 3, 9, 10, 11 | TG, HDL-C, BMI, TG:HDL-C |
| VPS37Da | 7 | 73665347..73672110 | rs371515311 | 73,660,465 | 6.1E-16 | yes | 1 | TG, HDL-C |
| DNAJC30 | 7 | 73680918..73683453 | rs3828973 | 73,682,169 | 1.3E-09 | yes | NA | TG |
| ABHD11a | 7 | 73736094..73738802 | rs10226706 | 73,751,424 | 3.6E-08 | yes | 5 | TG |
| CLDN3 | 7 | 73768997..73770270 | rs6460054 | 73,770,204 | 3.0E-08 | yes | NA | TG |
| TMEM270a | 7 | 73860848..73865890 | rs73144858 | 73,922,565 | 2.7E-13 | yes | 7 | NA |
| ELNa | 7 | 74028173..74069907 | rs188072556 | 73,999,294 | 1.3E-15 | yes | 10 | NA |
| RFC2 | 7 | 74231502..74254399 | rs148741166 | 74,252,973 | 1.2E-10 | yes | NA | TG |
| CLIP2 | 7 | 74289407..74405935 | rs151126504 | 74,392,493 | 1.0E-13 | yes | NA | NA |
| GTF2IRD1a | 7 | 74453906..74602605 | rs145049525 | 74,440,602 | 9.0E-09 | no | NA | TG, BMI, TG:HDL-C |
| TAD | CHR | Interval (b38) | -- | -- | -- | -- | -- | -- |
| pancreas | 7 | 73160000..74760000 | -- | -- | -- | -- | -- | -- |
| hippocampus | 7 | 73280000..74760000 | -- | -- | -- | -- | -- | -- |
| liver | 7 | 73280000..74760000 | -- | -- | -- | -- | -- | -- |
Tissues in TWAS: 1 = Adipose Subcutaneous; 2 = Adipose Visceral Omentum; 3 = Adrenal Gland; 4 = Brain Cortex; 5 = Brain Hippocampus; 6 = Brain Hypothalamus; 7 = Liver; 8 = Muscle Skeletal; 9 = Pancreas; 10 = Pituitary; 11 = Thyroid. Previous GWASs reported in the NHGRI-EBI GWAS Catalog have identified various phenotypes that reach genome-wide significance (P < 5 × 10−8). Coordinates for TADs were retrieved from the following source (http://3dgenome.fsm.northwestern.edu/publications.html).
AD Alzheimer’s disease, b38 Genome Research Consortium human build 38, BMI body mass index; CHR chromosome, FG fasting glucose, HDL-C high-density lipoprotein cholesterol, IR insulin resistance, NA not available, Pos position, T2D type 2 diabetes, TAD topologically associating domains, TG triglycerides, TG:HDLC the triglyceride to high-density lipoprotein cholesterol ratio, TWAS transcriptome-wide association analysis.
aNearby gene. -- not applicable. This GWAS analysis utilized BOLT-LMM’s mixed linear models with a two-sided chi-square test. The conventional genome-wide significance threshold of P < 5 × 10−8 was applied.