Rare nsSNPs frequency comparison between our sequencing results and a set of 1287 UK controls with exome sequence data generated by the UK10K project (http://www.uk10k.org) for the eight sarcomere genes most commonly associated with HCM
| Gene | Rare nsSNPs—Frequency in controls | Rare nsSNPs—Frequency in patients | p Value | 95% CI for the proportion of cases explained | Probability that a nsSNP is causal |
|---|---|---|---|---|---|
| MYH7 | 0.025 | 0.172 | 3.86E-13 | (0.096 to 0.207) | 0.856 |
| TNNT2 | 0.003 | 0.044 | 8.41E-05 | (0.014 to 0.071) | 0.930 |
| TNNI3 | 0.000 | 0.017 | 0.002 | (0.003 to 0.042) | 1.000 |
| MYBPC3 | 0.045 | 0.106 | 0.007 | (0.014 to 0.104) | 0.570 |
| MYL2 | 0.007 | 0.022 | 0.065 | (0 to 0.044) | NA |
| MYL3 | 0.004 | 0.011 | 0.208 | (0 to 0.0301) | NA |
| ACTC1 | 0.0008 | 0.006 | 0.230 | (0 to 0.0167) | NA |
| TPM1 | 0.000 | 0.006 | 0.123 | (0 to 0.0167) | NA |
To avoid technical artefacts associated with indel calling, and to properly match cases and controls, we restricted this analysis to nsSNPs and the 180 HCM UK Caucasian HCM cases. The columns show: the proportion of the 1287 UK controls with exome sequence data generated by the UK10K project (http://www.uk10k.org) and 180 HCM Caucasian cases that carry rare nsSNPs in these genes (rare defined by frequency less than 0.5% in the 1000 Genomes dataset), a Fisher exact test p value to quantify the case-control difference, the 95% CI for the estimated proportion of HCM cases explained by rare nsSNPs variants in each gene (see online supplementary statistical methods), and (in the rightmost column) the estimated probability that a rare nsSNP found in a HCM case in each gene is disease causing (see online supplementary statistical methods).
HCM, hypertrophic cardiomyopathy; nsSNP, non-synonymous single nucleotide polymorphism.