Figure 2

Manhattan plots illustrating negative log10 two-sided (a) F-test or (b) chi-squared p-values derived from the FGFP cohort Score test association analysis for (a) rank normal transformed (RNT) abundances and (b) presence/absence (Hurdle Binary) states. The genome-wide threshold is indicated by the horizontal dashed line. (c) Manhattan plot for our targeted meta-analysis derived from Expectation-Maximization (em) parameter estimates. Sites that did not exhibit consistent effect estimates in meta-analysis are shaded in grey, while those sites that had a smaller two-sided inverse-variance fixed-effect meta-p-value than the FGFP (em) p-value are colored in blue and red for P/A (HB) and RNT (AB) traits, respectively. Loci that achieved study-wide significance are highlighted by a blue tower, while those exceeding the genome-wide threshold are in shaded in grey. Dashed lines indicate the study-level (black), conventional genome-wide (grey), and target-meta analysis (red) thresholds of 1.57×10⁻¹⁰, 2.5×10⁻⁸, and 1×10^-5, respectively. LocusZoom plots of association results using the FGFP derived two-sided chi-squared (HB) or F-test (RNT) p-values for three top SNPs that achieved the conventional genome-wide level p-value in the meta-analysis (d-f). The LD estimates are color coded (D′ ≥0.3 to >0.4 in purple) and recombination rate is indicated by the blue lines and the z-axis. The proximal genes to the top SNPs are indicated in the bottom panel. Genotype to microbial trait structure for the tagged variant at each locus is illustrated in the insert, with (f) illustrating a boxplot (identifying the mean, first and third quartiles and the 95% confidence intervals) of taxon abundance by genotypic state (homozygous non-effect allele (0), heterozygous (1), or homozygous effect allele (2)), while (d) and (e) inserts illustrate bar plots of the proportion of individuals in each genotypic state where the taxon is absent (red) or present (blue) in each of the observed genotypic states. Genotypic state sample sizes are (d) n0=1113, n1=927, n2=219, (e) n0=2177, n1=82, (f) n0=1948, n1=292, n2=19. Data used to generate these plots can be found on data.bris https://doi.org/10.5523/bris.22bqn399f9i432q56gt3wfhzlc) and Table S2.