Table 2.
Variants that passed quality control filters in the primary analysis compared with the Global Lipids Genetics Consortium
| Gene | Chr | Positiona | rsID | Ref | Alt | Annotation | eMERGE cohort | GLGC metabochip | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MAF EA (%) | Beta | p-value LDL-C | MAF in 1kGP (%) | Betab | p-value | |||||||
| PCSK9 | 1 | 55505647 | rs11591147 | G | T | issense | 1.4 | −12.97 | 1.3 × 10−27 | 1.7 | −0.50 | 1.6 × 10−142 |
| 55519015 | rs639750 | T | G | Intron | 32.7 | −1.82 | 1.0 × 10−9 | – | – | – | ||
| APOB | 2 | 21233972 | rs533617 | T | C | Missense | 3.8 | −4.40 | 1.3 × 10−9 | 4.9 | −0.14 | 1.7 × 10−27 |
| 21263639 | rs531819 | G | T | Intron | 15.5 | −4.07 | 2.6 × 10−26 | 19.1 | −0.12 | 1.3 × 10−57 | ||
| 21263900 | rs1367117 | G | A | Missense | 31.6 | 3.52 | 6.4 × 10−32 | 71.2 | −0.11 | 1.4 × 10−75 | ||
| LDLR | 19 | 11202306 | rs6511720 | G | T | Regulatory intron | 11.4 | −5.79 | 4.2 × 10−39 | 9.8 | −0.23 | 2.8 × 10−151 |
| 11206575 | rs6511721 | A | G | Retained intron | 48.3 | 1.73 | 5.6 × 10−10 | 48.8 | −0.06 | 1.5 × 10−29 | ||
| 11227480 | rs2738447 | C | A | Nonsense mediated decay | 41.5 | −1.67 | 4.0 × 10−9 | 42.9 | −0.05 | 8.4 × 10−13 | ||
| 11231203 | rs72658867 | G | A | Splice regions | 1.1 | −10.20 | 2.8 × 10−14 | – | – | – | ||
| 11243445 | rs5742911 | A | G | 3′ UTR | 30.7 | −1.79 | 3.7 × 10−9 | 26.8 | −0.06 | 5.3 × 10−24 | ||
Selection criteria: Imputation quality r2 > 0.4; MAF > 1%; LCL-C association (threshold of 5.0 × 10−8); LD r2 < 0.3
GLGC Global Lipids Genetics Consortium, Chr chromosome number, Ref reference allele, Alt alternate allele, MAF minor allele frequency, LDL-C low-density lipoprotein cholesterol, 1kGP 1000 Genomes program
aPosition in human genome assembly hg19
bThe difference in Beta between eMERGE and GLGC is primarily due to differences in units of measurements. eMERGE used mg/dL while GLGC used mmol/L