Table 2. Summary of novel association signals.
| Variant and cohorts | Trait | Chr:pos (EA/NEA) | Nearest gene | Internal replication | EAF | Beta (SE) | P-value | Overall MAC (N) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Replication cohorts | EAF | Beta (SE) | P-value | MAC (N) | ||||||||
| chr16:70790626 MANOLIS | HDL | 16:70790626 (T/C) | VAC14-AS1 VAC14 | MANOLIS CoreExome | 0.003 | −1.885 (0.994) | 5.76 × 10−2 | 1.26 (210) | 0.006 | −1.713 (0.254) | 1.57 × 10−11 | 20 (1476) |
| MANOLIS OmniExome | 0.007 | −1.702 (0.263) | 1.81 × 10−10 | 17.6 (1255) | ||||||||
| rs145556679 MANOLIS | TG | 11:117643264 (C/G) | DSCAML1 | MANOLIS CoreExome | 0.005 | −1.293 (0.729) | 7.85 × 10−2 | 2.09 (209) | 0.013 | −1.134 (0.17) | 2.53 × 10−11 | 49 (1476) |
| MANOLIS OmniExome | 0.014 | −1.125 (0.175) | 1.70 × 10−10 | 35.1 (1252) | ||||||||
| VLDL | MANOLIS CoreExome | 0.005 | −1.365 (0.727) | 6.21 × 10−2 | 2.1 (210) | 0.013 | −1.131 (0.17) | 2.90 × 10−11 | ||||
| MANOLIS OmniExome | 0.014 | −1.118 (0.175) | 2.29 × 10−10 | 35.1 (1253) | ||||||||
| rs140087759 MANOLIS | WHR | 5:28292892 (T/C) | CTD-2061E9.1 | MANOLIS CoreExome | 0.015 | 1.676 (0.411) | 5.92 × 10−5 | 6.12 (204) | 0.01 | 1.189 (0.209) | 1.35 × 10−8 | 31 (1476) |
| MANOLIS OmniExome | 0.009 | 1.02 (0.243) | 2.90 × 10−5 | 18.8 (1047) | ||||||||
| rs13382259* Pomak | DBP | 2:113934176 (T/A) | PSD4 | Pomak CoreExome | 0.047 | 0.509 (0.126) | 6.98 × 10−5 | 60.3 (641) | 0.043 | 0.554 (0.1) | 3.18 × 10−8 | 172 (1737) |
| Pomak OmniExome | 0.039 | 0.629 (0.164) | 1.36 × 10−4 | 43 (551) | ||||||||
| rs6131100* Pomak | FGBMIadj | 20:10434530 (A/T) | SLX4IP | Pomak CoreExome | 0.038 | −0.573 (0.16) | 3.62 × 10−4 | 43.2 (569) | 0.037 | −0.79 (0.139) | 1.21 × 10−8 | 135 (1737) |
| Pomak OmniExome | 0.035 | −1.454 (0.279) | 7.12 × 10−7 | 12.2 (174) | ||||||||
| rs79748197 Pomak | WBC | 2:19430105 (G/A) | AC092594.1 | Pomak CoreExome | 0.004 | −1.242 (0.403) | 2.12 × 10−3 | 5.8 (725) | 0.008 | −1.156 (0.209) | 3.00 × 10−8 | 31 (1737) |
| Pomak OmniExome | 0.004 | −1.125 (0.243) | 4.14 × 10−6 | 20.9 (948) | ||||||||
| rs557129696 Pomak | HGB | 11:5328683 (G/T) | HBG2 HBE1 AC104389.28 | Pomak CoreExome | 0.002 | −1.95 (0.606) | 1.36 × 10−3 | 2.87 (717) | 0.004 | −2.027 (0.308) | 4.83 × 10−11 | 13 (1737) |
| Pomak OmniExome | 0.005 | −2.054 (0.358) | 1.30 × 10−8 | 9.45 (945) | ||||||||
| rs112037309* MANOLIS & Pomak | Weight | 4:106617136 (A/G) | ARHGEF38 INTS12 | MANOLIS | 0.075 | 0.295 (0.078) | 1.43 × 10−4 | 189.8 (1258) | 0.075 | 0.287 (0.052) | 2.70 × 10−8 | 485 (3213) |
| Pomak | 0.075 | 0.28 (0.07) | 5.96 × 10−5 | 250.8 (1672) | ||||||||
All variants are intronic with the exception of rs140087759 which is intergenic, variant consequences are taken from Ensembl (http://www.ensembl.org). For the internal replication the software used was GEMMA with the exception of rs112037309 in which METACARPA was used. Cohorts, cohorts from which the signal arose. Chr:pos, represents the chromosome and position in GRCh37/hg19 coordinates; EA, effect allele; NEA, non-effect allele; EAF, effect allele frequency; P-value, the likelihood ratio test P-value from GEMMA or Wald test P-value from METACARPA; MAC, minor allele count for samples in the analysis; Overall MAC, minor allele count for all samples in the cohorts from which the signal arose, established using the rounded imputed allele dosages from SNPTEST (https://mathgen.stats.ox.ac.uk/genetics_software/snptest/snptest.html); N, sample size; HDL, high-density lipoprotein cholesterol; DBP, diastolic blood pressure; TG, triglycerides; VLDL, very low-density lipoprotein cholesterol; FGBMIadjusted, fasting glucose adjusted for body mass index; HGB, haemoglobin; WBC, white blood cells; WHR, waist-to-hip ratio.
*At least one proxy is present in the International HapMap project data (http://hapmap.ncbi.nlm.nih.gov). Proxies were determined using LD (r2>0.8 in the cohorts used for the meta-analysis) for each novel variant. If a proxy was in HapMap it also had high LD (r2>0.9) with the variant in the 1000 Genomes Project CEU population3. LocusZoom was used to create the regional plots (http://csg.sph.umich.edu/locuszoom/).