Table 3.
Rare variants (AF <5%) discovered in WGS, WES and imputed studies and found to be associated with various traits
| Gene | Variant ID | Trait/disease | Samples | AF (cases/controls) | Beta/OR (SE)/(CI) | Type | Study | Population | Reference |
|---|---|---|---|---|---|---|---|---|---|
| PCSK9 | rs11591147 | LDL cholesterol | 3621 | 0.022 | –0.470 (0.085) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| PCSK9 | rs11591147 | LDL cholesterol | 6602 | 0.038 | –0.406 (0.053) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| PCSK9 | rs11591147 | Triglycerides | 6602 | 0.038 | –0.390 (0.053) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| EN1 | rs55983207 | BMD | 45,436 | 0.05 | 0.12 | WGS + WES + imputation | UK10K and others | European | http://www.ncbi.nlm.nih.gov/pubmed/26367794 |
| EN1 | rs11692564 | BMD | 40,516 | 0.016 | 0.22 | WGS + WES + imputation | UK10K and others | European | http://www.ncbi.nlm.nih.gov/pubmed/26367794 |
| EN1 | rs188303909 | BMD | 40,453 | 0.03 | 0.16 | WGS + WES + imputation | UK10K and others | European | http://www.ncbi.nlm.nih.gov/pubmed/26367794 |
| CCDC36 | rs202238847 | Height | 51,309 | 0.021 | 0.1091 (0.0233) | WGS + imputation | UK10K | British | Tachmazidou et al. (in press) |
| ADIPOQ | rs74577862 | Adiponectin | 3621 | 0.026 | –0.915 (0.091) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| ADIPOQ | rs17366653 | Adiponectin | 3621 | 0.01 | –1.029 (0.150) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| GHR | rs121909358 | Height | 6307 | 0.0087 (<0.0001) | –0.64 | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366551 |
| TMEM161B | rs774396010 | HDL cholesterol | 3621 | 0.001 | –1.887 (0.378) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| PAM | rs35658696 | Type 2 diabetes | 278,254 | 0.0498 | 1.22 | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/24464100 |
| GLP1R | rs10305492 | Fasting glucose | 60,564 | 0.01 | –0.09 (0.013) | GWAS + WES | CHARGE | African and European | http://www.ncbi.nlm.nih.gov/pubmed/25631608 |
| TREM2 | rs75932628 | Alzheimer’s disease | 110,050 | 0.0063 | 2.26 | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/23150908 |
| CCND3 | rs112233623 | MCV | 107,686 | 0.011 | 0.739 (0.05) | WGS + imputation | UK10K and others | European | https://www.ncbi.nlm.nih.gov/pubmed/27668658 |
| WNT16 | rs148771817 | BMD | 10,387 | 0.012 | 0.46 | WGS + WES + imputation | UK10K and others | European | http://www.ncbi.nlm.nih.gov/pubmed/26367794 |
| ABCA1 | rs3824477 | HDL cholesterol | 56,598 | 0.026 | 0.123 (0.016) | WGS + imputation | UK10K and others | European | https://www.ncbi.nlm.nih.gov/pubmed/27668658 |
| FNBP1 | rs528899443 | FEV1/FVC | 3621 | 0.004 | 1.078 (0.204) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| GFI1B | rs150813342 | PLT | 114,753 | 0.004 | –0.406 (0.026) | WGS + imputation | UK10K and others | European | https://www.ncbi.nlm.nih.gov/pubmed/27668658 |
| GFI1B | rs150813342 | PLT | 13,744 | 0.008 | –0.402 (0.07) | WES | Six cohort studies | European and African American | http://www.ncbi.nlm.nih.gov/pubmed/27486782 |
| ANK3 | rs141471070 | FEV1/FVC | 3621 | 0.006 | 0.739 (0.164) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| KCNQ1 | rs150199504 | Height | 6307 | 0.07 (<0.01) | –0.31 | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366551 |
| HBB | rs11549407 | Cholesterol, total | 6602 | 0.048 | –0.490 (0.05) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| HBB | rs11549407 | LDL cholesterol | 6602 | 0.048 | –0.473 (0.051) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| SMCO4 | rs111902751 | FVC | 3621 | 0.014 | –0.505 (0.103) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| APOA5 | rs778114184 | Triglycerides | 6602 | 0.025 | –0.450 (0.064) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| APOC3 | rs138326449 | Triglycerides | 3621 | 0.003 | –1.425 (0.265) | WGS | UK10K | British | dx.doi.org/10.1038/ncomms5871 |
| APOC3 | rs138326449 | Triglycerides | 3734 | 0.001 | NA | WES | ESP of NHLBI | European or African | http://www.ncbi.nlm.nih.gov/pubmed/24941081 |
| APOC3 | rs138326449 | VLDL | 3621 | 0.003 | –1.426 (0.265) | WGS | UK10K | British | dx.doi.org/10.1038/ncomms5871 |
| CCND2 | rs76895963 | Type 2 diabetes | 278,254 | 0.0147 | 0.53 | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/24464100 |
| VWF | rs61750625 | VWF antigen | 4468 | 0.00763 | –39.6 (9.71) | WES | ESP of NHLBI | European or African | http://www.ncbi.nlm.nih.gov/pubmed/23690449 |
| VWF | rs149424724 | VWF antigen | 4468 | 0.008 | –40.3 (10.0) | WES | ESP of NHLBI | European or African | http://www.ncbi.nlm.nih.gov/pubmed/23690449 |
| VWF | rs150077670 | VWF antigen | 4468 | 0.0044 | –34.5 (12.7) | WES | ESP of NHLBI | European or African | http://www.ncbi.nlm.nih.gov/pubmed/23690449 |
| MBIP | rs116909374 | TSH (thyrotropin) | 15,037 | 0.043 | –0.208 (0.032) | WGS + imputation | UK10K | British | DOI: 10.1038/ncomms6681 |
| SERPINA1 | rs28929474 | Height | 49,889 | 0.019 | 0.1346 (0.0253) | WGS + imputation | UK10K | British | Tachmazidou et al. (in press) |
| TP53BP1 | rs575505283 | PLT | 121,793 | 0.014 | –0.162 (0.019) | WGS + imputation | UK10K and others | European | https://www.ncbi.nlm.nih.gov/pubmed/27668658 |
| NPRL3 | rs117747069 | MCH | 120,851 | 0.037 | –0.176 (0.024) | WGS + imputation | UK10K and others | European | https://www.ncbi.nlm.nih.gov/pubmed/27668658 |
| CDH13 | rs12051272 | Adiponectin | 3621 | 0.009 | –1.074 (0.156) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| APOH | rs1801689 | PLT | 13,5097 | 0.033 | 0.104 (0.012) | WGS + imputation | UK10K and others | European | https://www.ncbi.nlm.nih.gov/pubmed/27668658 |
| ABCA6 | rs77542162 | Cholesterol, total | 35,000 | 0.034 | 0.14 | WGS + imputation | GoNL | Dutch | http://www.ncbi.nlm.nih.gov/pubmed/25751400 |
| ABCA6 | rs77542162 | LDL cholesterol | 35,000 | 0.034 | 0.135 | WGS + imputation | GoNL | Dutch | http://www.ncbi.nlm.nih.gov/pubmed/25751400 |
| B4GALT6 | rs113107469 | FT4 (free thyroxine) | 13,649 | 0.032 | 0.223 (0.037) | WGS + imputation | UK10K | British | DOI: 10.1038/ncomms6681 |
| C3 | rs147859257 | AMD | 52,578 | 0.0055 | 3.13 (1.99–4.91) | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/24036950 |
| LDLR | rs72658867 | ApoB | 3621 | 0.012 | –0.538 (0.119) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| LDLR | rs72658867 | LDL cholesterol | 3621 | 0.012 | –0.584 (0.112) | WGS | UK10K | British | http://www.ncbi.nlm.nih.gov/pubmed/26367797 |
| APOE | rs7412 | LDL cholesterol | 6602 | 0.036 | –0.645 (0.053) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| APOE | rs7412 | Triglycerides | 6602 | 0.036 | –0.544 (0.053) | WGS + imputation | SardiNIA | Sardinian | http://www.ncbi.nlm.nih.gov/pubmed/26366554 |
| APP | rs63750847 | Alzheimer’s disease | 71,743 | 0.00467 | 0.189 | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/22801501 |
| LGR4 | hg18_chr11:27369242_A | BMD | 95,085 | 0.00174 | –0.75 (0.16) | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/23644456 |
| PDX1 | hg18_chr13:27396636delT | Type 2 diabetes | 278,254 | 0.00198 | 2.47 | WGS + imputation | deCODE | Icelandic | http://www.ncbi.nlm.nih.gov/pubmed/24464100 |
AF allele frequency, AMD age-related macular degeneration, BMD, bone mineral density, CI confidence interval, ESP Exome Sequencing Project, FEV forced expiratory volume, FVC forced vital capacity, HDL high-density lipoprotein, LDL low-density lipoprotein, MCH mean cell haemoglobin, MCV mean cell volume, NA not applicable, NHLBI National Heart, Lung, and Blood Institute, OR odds ratio, PLT platelet count, SE standard error, WES whole-exome sequencing, WGS whole-genome sequencing, VLDL very low-density lipoprotein, VWF Von Willebrand factor