New genetic associations between rare or low-frequency variants and human complex traits identified using the ExomeChip
| Trait | Population | Sample size | Gene | Variant | Minor allele frequency | Effect size (in SD units) | GWAS locus | Reference |
|---|---|---|---|---|---|---|---|---|
| Insulin processing and secretion | Europeans (Finland) | 8229 | SGSM2 | rs61741902 (p.Val996Ile) | 1.4% | 0.41 | Yes, but independent from SNP | 64 |
| MADD | rs35233100 (p.Arg766X) | 3.7% | −0.32 | Yes, but independent from SNP | ||||
| TBC1D30 | rs150781447 (p.Arg279Cys) | 2.0% | 0.50 | No | ||||
| KANK1 | rs3824420 (p.Arg667His) | 2.9% | 0.28 | No | ||||
| PAM | rs35658696 (p.Asp563Gly) | 5.3% | −0.21 | No | ||||
| Alanine transaminase (a marker of liver injury) | EA, AA and HA | 882 (EA), 1324 (AA), 467 (HA) | TM6SF2 | rs58542926 (p.Glu167Lys) | 7.2% (EA), 3.4% (AA), 4.7% (HA) | 2.0 alanine transaminase unit | Yes, explain the GWAS signal | 71 |
| Blood lipids | EA and AA | 42 208 (EA), 14 330 (AA) | ANGPTL8 | rs145464906 (p.Gln121Stop) | 0.1% (EA), 0.01% (AA) | 0.77 | Yes, but independent from SNP | 69 |
| PAFAH1B2 | rs186808413 (p.Ser161Leu) | 1.1% (EA), 0.2% (AA) | 0.23 (HDL), −1.46 (TG) | Yes, but independent from SNPs | ||||
| COL18A1 | rs114139997 (p.Gly111Arg) | 0.003% (EA), 1.9% (AA) | 0.15 (HDL), −2.34 (TG) | No | ||||
| PCSK7 | rs142953140 (p.Arg504His) | 0% (EA), 0.2% (AA) | 1.31 (HDL), −4.39 (TG) | Yes, but independent from SNPs | ||||
| Europeans (Norway) | 10 309 | TM6SF2 | rs58542926 (p.Glu167Lys) | 8.9% | −0.19 (TC) | Yes, explain the GWAS signal | 70 | |
| Blood cell traits | EA, French Canadians and Europeans (Germany) | 31 340 | EPO | rs62483572 (p.Asp70Asn) | 0.4% | −0.22 (HCT), −0.21 (HGB) | Yes, but independent from SNP | 72 |
| TUBB1 | rs41303899 (p.Gly109Glu) | 0.2% | −0.49 (PLT) | Yes, but independent from SNP | ||||
| CXCR2 | 8 missense variants | 0.005%–0.5% | −0.23 (WBC) | No |
Otherwise noted, effect sizes are in SD units.
AA, African-Americans; EA, European Americans; HA, Hispanic Americans; HCT, haematocrit; HDL, high-density lipoprotein cholesterol; HGB, haemoglobin; PLT, platelet; SNP, single nucleotide variation; TC, total cholesterol; TG, triglycerides; WBC, white blood cell; GWAS, genome-wide association studies.