Table 2. Gene discovery using EigenGWAS.
Gene | Lead SNP | Position | Allele | P-valuea | MAF (TSI:CEU) | Fstb | Annotation |
---|---|---|---|---|---|---|---|
CEU and TSI samples | |||||||
LCT | rs6719488 | 2:135817629 | G/T | 6.68e−34 (1.21e−20) | 0.733:0.206 | 0.558 | Lactose persistent locus |
DARS | rs13404551 | 2:135964425 | C/T | 8.18e−39 (1.51e−23) | 0.756:0.206 | 0.604 | Genetic hitchhiking because of LCT |
MICA | rs2256175 | 6:31412672 | T/C | 8.94e−10 (2.60e−6) | 0.665:0.360 | 0.183 | MHC class I polypeptide-related sequence A |
HIF1A | rs2256205 | 14:61670944 | A/G | 1.51e−10 (8.86e−7) | 0.464:0.179 | 0.192 | HIF-1A thus plays an essential role in embryonic vascularization, tumour angiogenesis and pathophysiology of ischaemic disease. |
HERC2 | rs8039195 | 15:26189679 | C/T | 2.75e−12 (8.22e−08) | 0.403:0.122 | 0.212 | Genetic variations in this gene are associated with skin/hair/eye pigmentation variability |
Gene | Lead SNP | Position | Allele | P-valuea | MAF (Southern Europeans: Northern Europeans) | Fstb | Annotation |
POPRES European samples | |||||||
LCT | rs3754686 | 2:135817629 | T/C | 3.30e−106 (1.23e−22) | 0.514:0.279 | 0.110 | |
DARS | rs13404551 | 2:135964425 | C/T | 6.32e−102 (8.99e−22) | 0.518:0.293 | 0.106 | |
SLC4A4 | rs605203 | 6:31819235 | C/A | 8.94e−44 (5.77e−10) | 0.214:0.343 | 0.040 | Defects in this gene can cause sialidosis, a lysosomal storage disease |
HERC2 | rs1667394 | 15:26189679 | C/T | 3.90e−38 (8.15e−09) | 0.276:0.173 | 0.041 |
Abbreviations: GWAS, genome-wide association study; MAF, minor allele frequency; SNP, single-nucleotide polymorphism.
The P-value cutoff for CEU and TSI was 5.44e−08 (919 133 SNPs) and for POPRES was 7.76e−08 (643 995 SNPs) at genome-wide significance level of α=0.05. λGC=1.725 for CEU and TSI and λGC=5.00 for POPRES.
P-values without λGC correction, and with λGC correction in parentheses.
Fst is calculated by partitioning the sample into two groups upon E1 >0. For TSI and CEU set, partitioning on E1 perfectly separated TSI (88 samples) and CEU (112 samples). For POPRES, partitioning on E1 separated southern European population (1092 samples) and northern European population (1374 samples).