Table 2.
Genetic effect estimates, PheWAS results, tissue expression, and relevant drug targets of eight proteins showing genetic effects on BMI
| Protein | Gene name | SNP Information | CKB cis-pQTL | Two-sample SMRb | CKB Obs. resultsd | UKB replicatione | PheWAS associationsf | Levels of expressiong | Drug target | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| rsID | EAa | EAFa | Beta (SE) | P | Beta (SE)c | P | Beta (SE) | P | Adipose | Brain | Liver | Pancreas | Intestine | |||||
| ITIH3 | ITIH3 | rs2286797 | G | 0.76 | 0.73 (0.033) | 7.9E − 107 | − 0.026 (0.006) | 9.9E − 06 | − 0.191 (0.016) | 4.0E − 33 | √ | BMI (↓) | + | + | +++ | + | + | – |
| LRP11 | LRP11 | rs9688902 | T | 0.72 | 0.662 (0.03) | 4.7E − 113 | 0.03 (0.007) | 8.5E − 06 | 0.126 (0.016) | 6.4E − 16 | – | Hand grip strength (↓), BMI (↑) | ++ | ++ | + | + | + | – |
| SCAMP3 | SCAMP3 | rs4971072 | A | 0.27 | 0.185 (0.026) | 1.0E − 12 | 0.115 (0.027) | 2.7E − 05 | 0.159 (0.015) | 1.5E − 24 | – | BMI (↑) | ++ | ++ | ++ | ++ | ++ | – |
| NUDT5h | NUDT5 | rs7100710 | A | 0.47 | 0.154 (0.023) | 2.4E − 11 | -0.122 (0.029) | 3.8E − 05 | 0.159 (0.015) | 1.8E − 25 | – | BMI (↓) | ++ | + | ++ | + | ++ | – |
| OGN | OGN | rs7023004 | G | 0.26 | 0.466 (0.039) | 1.5E − 80 | 0.033 (0.009) | 3.2E − 04 | 0.092 (0.018) | 2.6E − 07 | √ | Impedance of arm/leg/whole body (↓), height (↓) | +++ | + | + | + | + | – |
| EFEMP1 | EFEMP1 | rs58680090 | A | 0.75 | 0.166 (0.028) | 4.3E − 09 | 0.11 (0.031) | 4.7E − 04 | 0.037 (0.018) | 3.8E − 02 | – | Height (↓), trunk/body fat-free mass (↓), basal metabolic rate (↓), weight (↓) | +++ | + | + | + | ++ | – |
| TXNDC15 | TXNDC15 | rs3733897 | G | 0.38 | 1.045 (0.025) | 2.0E − 317 | 0.012 (0.004) | 4.5E − 04 | 0.003 (0.015) | 0.859 | √ | Height (↓) | ++ | ++ | + | ++ | ++ | – |
| PRDX6 | PRDX6 | rs61826753 | A | 0.33 | 0.37 (0.025) | 1.8E − 51 | 0.036 (0.011) | 6.8E − 04 | 0.084 (0.015) | 5.4E − 08 | – | – | +++ | +++ | +++ | +++ | +++ | – |
2SMR two sample Mendelian randomization; EA effect allele; EAF effect allele frequency; KO knockout
aEA referred to the allele associated with increased protein levels in CKB, and EAF was obtained from Biobank Japan
b2SMR: cis-pQTL obtained from CKB, with lookups in Biobank Japan for GWAS summary statistics
cBeta and SE were calculated using Wald ratio method
dObservation results in CKB in direction of protein-to-BMI
e2SMR: cis-pQTL obtained from UKB, with lookups in GIANT for GWAS summary statistics
fTraits or diseases in bold: P < 5 × 10–8, others were P < 5 × 10–6
gLevels of expression was estimated using GTEx and categorized into three groups as denoted: + (low); ++ (moderate) and +++ (high)
hSignificant in both directions (protein-to-BMI and BMI-to-protein)