Extended Data Fig. 6: Genotyping and mutability of AMY1 copy number and replication of associations with oral health.
From: Human and bacterial genetic variation shape oral microbiomes and health
a, Estimated diploid copy number of AMY1 for SPARK participants (n = 12,519). b, Concordance of AMY1 copy number estimates between 5,149 sibling pairs in the UKB cohort that share both haplotypes identical-by-descent (IBD2) in the region surrounding the amylase locus. Among the 5,149 IBD2 sibling pairs, 13 had copy number-discordant calls (red points) that tended to differ by two copies (11/13), likely corresponding to de novo duplication or deletion of a copy of the common structural cassette containing two AMY1 genes in an inverted orientation to each other (Fig. 3a). Several IBD2 sibling pairs with AMY1 copy number estimates that differed by close to 1 copy appeared more likely to reflect uncertainty in copy number estimates as they lacked a corresponding AMY2A duplication or deletion that would be expected to accompany a duplication or deletion of a single copy of AMY1. This gives an estimated germline mutation rate of 6.3x10−4 mutations/meiosis ([3.5x10−4,11.1x10−4], 95% CIs, similar to recent estimates from haplotype coalescent trees46), exceeding the mutation rate of most short tandem repeats88. c, Analogous to a, for the AoU cohort (n = 245,377). d, Odds ratios for risk of complete tooth loss in AoU (n = 230,002) per AMY1 diploid copy number. e, Analogous to d, for having caries. f, Odds ratios for risk of dentures use in UKB (n = 418,039) per AMY2A diploid copy number. g, Analogous to f, for AMY2B diploid copy number. Error bars, 95% CIs in all panels. P-values were computed using two-sided linear regression (d,e).
