Variants in two genomic regions were found to be associated with cotinine levels, including 15q25.1 (a region previously identified in association with smoking quantity134) and a locus at 4q13.2 (see Figs 1 and 2, Table 1, Table S2). All 96 variants that met or exceeded the threshold for genome-wide significance (p < 5 × 10−8) on chromosome 4 lay between 69.6 and 69.9 Mb within a region of UGT genes, including UGT2B10 and UGT2A3 (see Fig. 2). The variant with the lowest p-value in this region was rs114612145 (rs77107237 in GRCh38) (p = 5.89 × 10−10), which lies between UGT2B10 and UGT2A3 (Table 1, Fig. 2). The minor allele (G) was associated with a 0.22 SD increase in cotinine level, equating to ~39 ng/ml increase in plasma/serum cotinine (Table 1, Fig. 2). The cotinine quantification method did not affect the result. This SNP accounted for 0.87% of the variance in cotinine levels.
