Two additional interesting genes were highlighted. Egl-9 Family Hypoxia-Inducible Factor 2 (EGLN2) is a key component of the oxygen-sensing pathway that regulates the expression of various downstream genes, and responses e.g. to carbon monoxide (CO) and cigarette smoke exposure. In a recent study, EGLN2 was associated with CPD and breath CO independent of CYP2A6, although it was not associated with nicotine metabolism [62]. The top-SNP in EGLN2 (rs76443752) is in LD with all of the independent CYP2A6 variants (D’ = 0.67–1.00). Another potentially interesting candidate is Numb Homolog (Drosophila)-Like (NUMBL) which encodes a protein that maintains progenitor cells during cortical neurogenesis [63] and has previously been implicated in lung cancer [64, 65]. The top-SNP in NUMBL (rs4802082) is in LD with all of the independent variants (D’ = 0.48–0.96).
