Table 1.
Summary of top variants in the GCKR 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 |
|---|---|---|---|---|---|---|---|---|
| DPYSL5 | 2 | 26847995..26950351 | rs72804857 | 26,938,608 | 7.8E-11 | no | NA | TG, HDL-C, FG, BMI, TG:HDL-C |
| MAPRE3 | 2 | 26970637..27027219 | rs10207573 | 27,020,067 | 4.0E-09 | no | 1, 3 | TG, HDL-C, TG:HDL-C |
| TMEM214 | 2 | 27032965..27041694 | rs2304713 | 27,035,893 | 3.5E-10 | yes | NA | NA |
| AGBL5 | 2 | 27050364..27070618 | rs70953845 | 27,064,781 | 2.1E-10 | yes | 1, 5 | TG |
| OST4a | 2 | 27070472..27071654 | rs4665943 | 27,073,017 | 1.8E-08 | yes | 7 | NA |
| EMILIN1 | 2 | 27078615..27086403 | rs2304682 | 27,084,901 | 1.8E-09 | yes | 2 | NA |
| KHK | 2 | 27086772..27100762 | rs6714547 | 27,098,338 | 6.2E-11 | yes | 2, 8, 9, 10, 11 | NA |
| CGREF1 | 2 | 27099353..27119128 | rs6746337 | 27,118,195 | 2.6E-11 | yes | 5 | TG |
| ABHD1 | 2 | 27123815..27130812 | rs4665946 | 27,125,063 | 2.3E-21 | yes | 1, 2, 7, 8 | NA |
| PREB | 2 | 27130756..27134636 | rs71401560 | 27,131,111 | 1.6E-15 | yes | 2, 9, 10 | NA |
| PRR30 | 2 | 27136848..27139410 | rs11121 | 27,137,019 | 1.3E-15 | yes | NA | TG |
| TCF23 | 2 | 27149004..27156974 | rs1275513 | 27,148,102 | 7.9E-18 | yes | NA | TG |
| SLC5A6a | 2 | 27199587..27212787 | rs74684611 | 27,191,771 | 2.3E-21 | yes | 8 | TG, HDL-C |
| CADa | 2 | 27217369..27243943 | rs118130043 | 27,245,399 | 3.8E-13 | yes | 3 | TG |
| TRIM54 | 2 | 27282429..27307435 | rs189387480 | 27,292,538 | 5.9E−12 | yes | NA | TG |
| MPV17 | 2 | 27309492..27323097 | rs146502189 | 27,322,314 | 3.3E-13 | yes | 8 | TG |
| GTF3C2 | 2 | 27325854..27356764 | rs201232671 | 27,348,271 | 6.4E-14 | yes | 1 | TG |
| PPM1G | 2 | 27381199..27409591 | rs79803862 | 27,399,271 | 4.0E-22 | yes | 6, 8, 9 | TG, FG, BMI |
| NRBP1a | 2 | 27427790..27442259 | rs147530299 | 27,419,228 | 2.2E-23 | yes | 5 | TG, FG, BMI |
| IFT172 | 2 | 27444377..27489743 | rs117414910 | 27,455,222 | 1.8E-17 | no | 1, 10, 11 | TG, TG:HDL-C |
| GCKR | 2 | 27496839..27523684 | rs1260326 | 27,508,073 | 4.3E-204 | no | 5, 11 | IG, TG, T2D, FG, BMI, TG:HDL-C |
| SPATA31H1 | 2 | 27537386..27582722 | rs1919127 | 27,578,626 | 6.9E-114 | yes | 1, 2, 4, 9, 11 | NA |
| ZNF512 | 2 | 27583042..27623217 | rs12989678 | 27,598,615 | 1.3E-115 | yes | NA | TG, T2D |
| GPN1 | 2 | 27628247..27651511 | rs34502053 | 27,631,657 | 7.9E-68 | yes | 4, 8, 10, 11 | TG, BMI |
| SUPT7L | 2 | 27642568..27663614 | rs4666010 | 27,655,819 | 9.9E-45 | yes | 1, 5, 6, 9, 10, 11 | NA |
| SLC4A1AP | 2 | 27663889..27694969 | rs13021208 | 27,678,861 | 1.6E−57 | yes | 6, 10 | TG |
| MRPL33 | 2 | 27771719..27779733 | rs3792252 | 27,773,064 | 2.2E-37 | yes | 2, 8, 9 | TG, FG |
| RBKS | 2 | 27781379..27890387 | rs898034 | 27,867,953 | 1.5E-38 | yes | 8, 11 | TG |
| BABAM2 | 2 | 27888709..28338901 | rs141361525 | 27,896,053 | 8.7E-18 | yes | 1, 2, 11 | TG, HDL-C, FG. BMI |
| TAD | CHR | Interval (b38) | -- | -- | -- | -- | -- | -- |
| pancreas | 2 | 25920000..27320000 | -- | -- | -- | -- | -- | -- |
| pancreas | 2 | 27680000..28520000 | -- | -- | -- | -- | -- | -- |
| hippocampus | 2 | 25360000..27360000 | -- | -- | -- | -- | -- | -- |
| hippocampus | 2 | 27680000..28480000 | -- | -- | -- | -- | -- | -- |
| liver | 2 | 25920000..27320000 | -- | -- | -- | -- | -- | -- |
| liver | 2 | 27360000..28520000 | -- | -- | -- | -- | -- | -- |
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 (https://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.