Four of the five unreported novel HR-SNVs or their proxies (r2 > 0.8) are non-synonymous SNVs in TESK2, DALRD3, C10orf71 and SEC31B (Table 1A). The non-synonymous SNV in SEC31B (rs2295774, c.1096T>G, p.Ser332Ala) is in a conserved region of the protein, and is predicted to be damaging using three different algorithms in ANNOVAR (19). We also investigated whether the novel HR-associated SNVs or their proxies (r2 > 0.8) were associated with changes in expression levels of nearby genes (i.e. as expression quantitative trait loci, or eQTLs) in the Genotype-Tissue Expression database (GTEx) dataset (20). We observed a significant eQTL association at one novel HR locus (Supplementary Material, Table S8). Specifically, the HR increasing allele of the non-synonymous SNV at SEC31B was associated with increased levels of SEC31B in tibial nerves (P = 8.08 × 10−33), lung (P = 1.22 × 10−23), atrial appendage tissue (P = 4.56 × 10−11) and the left ventricle (P = 4.0 × 10−9), tissues which may be regarded as physiologically relevant for HR.
