Table 3. Top associated genes across high-risk pedigrees and individuals.
| Gene | SNP; locus | Variant; AA change | Phevor score | Phevor P-value | Frequency in asthma risk group, % (n=28) | Freq in CEU/GBR, % (n=183) | pVAAST P-value vs CEU/GBR | Freq in other UT suicides, % (n=432) | pVAAST P-value vs UT suicides | dbSNP freq, % | PolyPhen2 score | SIFT score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BDNF | rs66866077; chr11:27720937 | C/T; E/K | 3.46 | 0.0003 | 12.50 | 5.60 | 0.0314 | 4.10 | 0.00709 | 1.90 | 0.938 (possibly damaging) | 0.000 (damaging) |
| HNRNPA0 | rs201570235; chr5:137088945 | C/T; S/G | 2.85 | 0.0014 | 7.10 | 0.82 | 0.000704 | 1.70 | 0.0147 | 0.64 | 0.138 (benign) | 0.351 (tolerated) |
| FFAR2 | rs139764605; chr19:35941368 | G/A; S/N | 2.75 | 0.0018 | 3.60 | 0 | 0.0247 | 0 | 0.016 | 0.09 | 0.117 (benign) | 0.152 (tolerated) |
| ACVR1C | rs7594480; chr2:158390468 | T/C; I/V | 2.67 | 0.0021 | 16.10 | 6.80 | 0.022 | 5.70 | 0.00967 | 14.05 | 0.017 (benign) | 0.007 (damaging) |
| HOXB2 | rs200503077; chr17:46620525 | G/C; L/V | 2.54 | 0.0029 | 3.60 | 0 | 0.0207 | 0.10 | 0.0357 | NA | 1.00 (probably damaging) | 0.002 (damaging) |
| SMPD2 | rs1048197; chr6:109762332 | C/T; P/L | 2.48 | 0.0033 | 8.92 | 2.46 | 0.0106 | 2.66 | 0.00935 | 10.30 | 0.011 (benign) | 0.165 (tolerated) |
| AGRP | rs5030980; chr16:67516945 | C/T; A/T | 2.35 | 0.0045 | 10.70 | 3.28 | 0.03 | 3.48 | 0.0213 | 2.39 | 0.074 (benign) | 1.00 (tolerated) |
| OLR1 | rs11053646; chr12:10313448 | C/G; K/N | 2.1 | 0.0079 | 19.60 | 10.10 | 0.032 | 9.14 | 0.014 | 13.20 | 0.928 (possibly damaging) | 0.115 (tolerated) |
| CRCT1 | rs73004856; chr1:152487917 | G/A; G/S | 2.08 | 0.0083 | 3.60 | 0 | 0.0357 | 0.10 | 0.0399 | 5.10 | 0.129 (benign) | NA |
Abbreviations: ACVR1C, activin A receptor, type 1C; AGRP, agouti-related protein homolog; BDNF, brain-derived neurotrophic factor; CEU, western European ancestry; CRCT1, cysteine-rich C-terminal 1; dbSNP, NCBI single-nucleotide polymorphism database; FFAR2, free fatty acid receptor 2; GBR, British in England and Scotland; HNRNPA0, heterogeneous nuclear ribonucleoprotein A0; HOXB2, homeobox B2; NA, not available; OLR1, oxidized low density lipoprotein receptor 1; Phevor, phenotype driven variant ontological re-ranking tool; pVAAST, pedigree extension of the Variant Annotation, Analysis and Search Tool; SMPD2, neutral sphingomyelinase 2; SNP, single-nucleotide polymorphism; UT, Utah.
All pVAAST P-values were computed using 109 permutations. Frequencies (freq) between each group were calculated using chromosome counts, accounting for subjects with no calls. No homozygotes were observed for these variants. Frequencies and dbSNP were found at www.ncbi.nlm.nih.gov/projects/SNP/.