Extended Data Fig. 3: Results of the multi-ancestry GWAS meta-regression for brain age gap.

Manhattan plots (a-c) and quantile-quantile (QQ) plots (d-f) show the results of the multi-ancestry meta-regression (MR-MEGA) for the three brain age gap traits (up to N = 56,348). Multi-ancestry analyses combine results from the discovery sample (n = 32,634) and up to seven replication samples: UKB African ancestry (n = 337), UKB Admixed American ancestry (n = 94); UKB Central/South Asian ancestry (n = 638), UKB East Asian ancestry (n = 291), UKB European ancestry (n = 20,423), UKB Middle Eastern ancestry (n = 98), and LIFE-Adult (European ancestry; n = 1,833). Manhattan plots show the P values (-log₁₀ scale) of the tested genetic variants on the y-axis and base-pair positions along the chromosomes on the x-axis. P values were derived from two-sided linear regression models using PLINK, followed by meta-regression using MR-MEGA. The solid horizontal line indicates the threshold of genome-wide significance (p = 5.0e-08, two-sided, accounting for multiple testing). Pseudoautosomal variations have been added to chromosome ‘X’. Index variants are highlighted by diamonds and were identified by positional clumping with 3,000 kb window-size (no LD threshold was applied in multi-ancestry analyses). Quantile-quantile plots show the observed P values from the association analysis vs. the expected P values under the null hypothesis of no effect (-log₁₀ scale). For illustrative reasons, the y-axis has been truncated at p = 1.0e-40. a,d grey matter brain age gap (Manhattan and QQ); b,e white matter brain age gap (Manhattan and QQ); c,f combined brain age gap (Manhattan and QQ).