Table 2.
Genetic Loci in Which Single-Nucleotide Polymorphisms Associated With Echocardiographic Traits With P<5×10−7 (Stage 1) and Replication of These SNPs (Stage 2)
| Echocardiographic Trait | SNP | Locusa | SNP Type | Nearest Genea | Major/Minor Allele (Minor Allele Frequency)b | Stage 1 | Stage 2, One-sided P Valuee | Stages 1 + 2, Meta-analysis P Valued | |
|---|---|---|---|---|---|---|---|---|---|
| Effect Size (SE)c | Meta-analysis P Valued | ||||||||
| LV mass, gm | rs17568359 | 14q12 | Intergenic | NOVA1 | G/C (0.07) | −4.78 (0.89) | 8.53 × 10−8 | DNR | 1.66 × 10−5 |
| rs7565161 | 2p21 | Intergenic | CALM2 | G/A (0.40) | −3.01 (0.59) | 3.19 × 10−7 | DNR | 9.64 × 10−5 | |
| rs8031633 | 15q14 | Intergenic | MEIS2 | T/C (0.006) | 16.62 (3.27) | 3.71 × 10−7 | Not done | - | |
| LV internal diastolic dimensions, cm | rs89107 | 6q22 | Intragenic | SLC35F1 | A/G (0.50) | −0.03 (0.005) | 1.14 × 10−8 | .003e | 1.21 × 10−9 |
| rs11153768 | 6q22 | Intragenic | C6orf204, PLN | C/T (0.45) | 0.03 (0.005) | 4.61 × 10−7 | .002e | 1.67 × 10−8 | |
| LV wall thickness, cm | rs7910620 | 10q23 | Intragenic | GRID1 | C/G (0.009) | 0.17 (0.03) | 5.62 × 10−9 | NS | 6.69 × 10−7 |
| rs2059238 | 16q23 | Intragenic | WWOX | C/A (0.22) | −0.02 (0.004) | 1.89 × 10−7 | NS | 2.84 × 10−6 | |
| rs17132261 | 5q21 | Intergenic | SLC25A46 | C/T (0.015) | 0.060 (0.01) | 3.36 × 10−7 | .37 | 9.32 × 10−7 | |
| LV systolic dysfunction | rs2235487 | 16p13 | Intragenic | HN1L | A/G (0.22) | −0.38 (0.07) | 1.98 × 10−7 | .10 | 6.53 × 10−5 |
| Aortic root size, cmf | rs10852932 | 17p13 | Intragenic | SMG6 | G/T (0.36) | 0.03 (0.005) | 4.32 × 10−11 | .04e | 2.33 × 10−11 |
| rs4523957 | 17p13 | Intragenic | SRR | T/G (0.38) | 0.03 (0.005) | 1.87 × 10−10 | .01e | 3.25 × 10−11 | |
| rs413016 | 17p13 | Intragenic | TSR1 | C/T (0.25) | 0.03 (0.005) | 3.34 × 10−7 | .16 | 4.11 × 10−7 | |
| rs17608766 | 17q21 | Intragenic | GOSR2 | T/C (0.13) | 0.04 (0.007) | 1.43 × 10−7 | .48 | 1.04 × 10−5 | |
| rs7543130 | 1p21 | Intergenic | PALMD | C/A (0.49) | 0.03 (0.004) | 8.08 × 10−9 | .26 | 1.09 × 10−7 | |
| rs17470137 | 5q23 | Intergenic | CCDC100 | G/A (0.29) | 0.03 (0.005) | 1.63 × 10−8 | < .001e | 1.26 × 10−11 | |
| rs4026608 | 12q14 | Intergenic | HMGA2 | T/C (0.38) | −0.03 (0.005) | 7.30 × 10−8 | .004e | 1.75 × 10−9 | |
| rs10770612 | 12p12 | Intergenic | PDE3A | A/G (0.19) | 0.03 (0.007) | 2.40 × 10−7 | .002e | 2.43 × 10−8 | |
| rs893817 | 15q24 | Intragenic | LOXL1 | A/G (0.34) | 0.02 (0.005) | 4.12 × 10−7 | .44 | 2.78 × 10−6 | |
Abbreviations: DNR, did not replicate; LV, left ventricular; SNP, single-nucleotide polymorphisms.
See eTables 4 through 9 (available at http://www.jama.com) for exact location. No replication attempted for rs8031633 because of low minor allele frequency. Note that the 18 SNPs likely represent 16 genetic loci: rs89107 and rs11153768 are correlated (r2=0.5), as are rs10852932 and rs4523957 (r2=0.84) and so may represent the same loci, but are shown separately in the table because they are in different genes.
Alleles for the SNP on the forward strand of human genome reference sequence (National Center for Biotechnology Information Build 36) were modeled.
Effect-size estimates are shown as β coefficient (SE), which represents the change in echocardiographic measure in the units shown in the first column (or log-odds in the case of LV dysfunction) per unit difference in minor allele dose.
Inverse variance-weighted meta-analysis performed as detailed in the “Methods” section.
SNPs that replicated (based on 1-sided P<.05). DNR indicates that the β was in the opposite direction (no P values provided as tests were 1-sided).
Only 4 studies in stage 1 (Cardiovascular Heart Study, Rotterdam Study, Cooperative Health Research in the Region of Augsburg study, Framingham Heart Study) contributed to genome-wide association of aortic root size.