Table 3.
Summary of top variants in the APOA5 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 |
|---|---|---|---|---|---|---|---|---|
| BUD13 | 11 | 116748173..116772987 | rs6589565 | 116,769,521 | 7.3E-445 | yes | 8 | TG, HDL-C |
| ZPR1 | 11 | 116773799..116788023 | rs10750096 | 116,786,072 | 3.4E-451 | no | NA | TG, HDL-C, TG:HDL-C |
| APOA5 | 11 | 116789367..116792420 | rs651821 | 116,791,863 | 1.4E-919 | no | 9 | TG, HDL-C, TG:HDL-C |
| APOA4 | 11 | 116820700..116823304 | rs5104 | 116,821,618 | 1.1E-235 | no | 8, 11 | TG, HDL-C, TG:HDL-C |
| APOC3 | 11 | 116829907..116833072 | rs5128 | 116,832,924 | 2.8E-152 | yes | 6 | TG, HDL-C |
| APOA1 | 11 | 116835751..116837622 | rs12718464 | 116,836,685 | 3.1E-39 | yes | 2, 6, 7, 10 | TG, HDL-C, BMI |
| SIK3 | 11 | 116843402..117098428 | rs6589574 | 116,859,922 | 1.2E-112 | no | 1, 2, 5, 6, 8, 10 | TG, HDL-C, BMI, TG:HDL-C |
| PAFAH1B2 | 11 | 117144287..117178173 | rs7925256 | 117,174,619 | 8.0E-75 | yes | 5, 9 | TG, HDL-C, BMI |
| SIDT2 | 11 | 117178743..117197442 | rs6589603 | 117,185,123 | 1.1E-59 | yes | 1, 2, 3, 4, 6, 9, 10, 11 | TG, HDL-C |
| TAGLN | 11 | 117199294..117207465 | rs12970 | 117,203,393 | 6.1E-40 | yes | 4, 8, 9 | TG, HDL-C |
| PCSK7 | 11 | 117204337..117232073 | rs236911 | 117,214,554 | 5.3E-56 | no | 1, 2, 7, 11 | TG, HDL-C, BMI, TG:HDL-C |
| RNF214 | 11 | 117232671..117286454 | rs200694867 | 117,244,658 | 6.3E-28 | yes | NA | TG, HDL-C |
| BACE1 | 11 | 117285698..117316256 | rs3741288 | 117,315,499 | 4.2E−12 | yes | 2 | TG, HDL-C |
| CEP164 | 11 | 117321778..117413266 | rs11216364 | 117,355,903 | 1.2E-34 | no | 5, 10 | TG, HDL-C, BMI, TG:HDL-C |
| DSCAML1a | 11 | 117427772..117817514 | rs7115491 | 117,424,434 | 8.6E-17 | no | NA | TG, HDL-C, TG:HDL-C |
| TAD | CHR | Interval (b38) | -- | -- | -- | -- | -- | -- |
| pancreas | 11 | 116760000..119360000 | -- | -- | -- | -- | -- | -- |
| hippocampus | 11 | 116760000..117200000 | -- | -- | -- | -- | -- | -- |
| hippocampus | 11 | 117200000..118960000 | -- | -- | -- | -- | -- | -- |
| liver | 11 | 116720000..117200000 | -- | -- | -- | -- | -- | -- |
| liver | 11 | 117360000..118120000 | -- | -- | -- | -- | -- | -- |
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.