Table 4. Genetic loci where common SNPs are associated with blood high-density lipoprotein cholesterol.
| Combined analysis; GWAS & ≤3 Replications | GWAS: DGI | Replication 1: MDC-CC |
Replication 2: FINRISK97 |
Replication 3: NORDIL |
|||||
|---|---|---|---|---|---|---|---|---|---|
| P | P | P | P | P | |||||
| β | β | β | β | β | |||||
| SNP | Locus | SNP type | Nearest gene(s) | Allele (frequency)a | (s.e.m.)b | (s.e.m.) | (s.e.m.) | (s.e.m.) | (s.e.m.) |
| Newly identified locus | |||||||||
| rs4846914 | 1q42 | Intronic | GALNT2 | G (0.40) | 2 × 10−13 | 3 × 10−4 | 1 × 10−6 | 1 × 10−4 | 0.01 |
| −0.07 (0.01) | −0.10 (0.03) | −0.10 (0.02) | −0.06 (0.02) | −0.05 (0.02) | |||||
| Loci with prior evidence | |||||||||
| rs3890182 | 9q31 | Intronic | ABCA1 | A (0.13) | 3 × 10−10 | 3 × 10−5 | 0.003 | 0.001 | 0.02 |
| −0.10 (0.02) | −0.17 (0.04) | −0.09 (0.03) | −0.09 (0.03) | −0.08 (0.03) | |||||
| rs28927680c | 11q23 | 5′ upstream |
APOA1-C3-A4-A5, ZNF259, BUD13 |
G (0.07) | 2 × 10−5 | 0.31 | 6 × 10−6 | - | - |
| −0.13 (0.03) | −0.06 (0.05) | −017 (0.04) | |||||||
| rs1800775 | 16q13 | 5′ upstream | CETP | C (0.51) | 1 × 10−73 | 3 × 10−13 | 2 × 10−29 | 1 × 10−23 | 2 × 10−12 |
| −0.18 (0.01) | −0.20 (0.03) | −0.22 (0.02) | −0.17 (0.02) | −0.14 (0.02) | |||||
| rs1800588 | 15q21 | 5′ upstream | LIPC | T (0.21) | 2 × 10−32 | 3 × 10−5d | 4 × 10−10 | 8 × 10−17 | 3 × 10−5 |
| 0.14 (0.01) | 0.15 (0.03) | 0.15 (0.02) | 0.16 (0.02) | 0.10 (0.02) | |||||
| rs2156552 | 18q21 | Intergenic | LIPG, ACAA2 | A (0.18) | 2 × 10−7 | 0.02 | 0.02 | 0.001 | 0.03 |
| −0.07 (0.01) | −0.09 (0.03) | −0.06 (0.03) | −0.07 (0.02) | −0.06 (0.03) | |||||
| rs328 | 8p21 | Coding | LPL | G (0.09) | 9 × 10−23 | 3 × 10−4d | 3 × 10−12 | 1 × 10−6 | 6 × 10−5 |
| 0.17 (0.02) | 0.17 (0.05) | 0.23 (0.03) | 0.14 (0.03) | 0.14 (0.04) | |||||
A dash (-) indicates that we did not genotype that SNP in sample, Beta-coefficient (β) represents the proportion of 1 s.d. change in standardized HDL cholesterol residual (mean = 0, s.d. = 1 after adjustment for age, age2, gender and diabetes status) per copy of the allele modeled.
Alleles for the SNP on the forward strand of human genome reference sequence (National Center for Biotechnology Information Build 35) were modeled. Allele frequency in the MDC-CC sample is presented.
Variance-weighted meta-analysis performed using data from up to four samples (DGI, MDC-CC, FINRISK and NORDIL), as described in Methods.
rs28927680 is highly correlated with APOA1-APOC3-APOA4-APOA5 coding SNP rs3133506 (r2 = 0.98 in MDC-CC); SNP rs3133506 (also known as 56C>G) has been reproducibly related to HDL cholesterol and triglyceride concentrations.
Association data from imputed SNP genotypes.