In the UKB sibling hold-out sample, we conducted analyses of the genome-wide EXT polygenic scores with 37 phenotypes from the domains of (a) risky behavior, (b) overall and reproductive health, (c) cognitive ability, (d) personality, and (e) socioeconomic status (Supplementary Information section 5.2.5; Supplementary Table 34). We evaluated the per-category mean of the standardized difference between βWF and β, and found that within-family estimates were, on average, the same for the risky behavior category (mean attenuation = 0.08; 95% CI: −1.67 to 1.83), and only attenuated modestly for personality (mean attenuation = −0.35; 95% CI: −1.06 to 0.36). However, the within-family estimates attenuated more for cognitive ability (mean attenuation −6.55; 95% CI: −9.93 to −3.17), socioeconomic status (mean attenuation −2.43; 95% CI: −4.39 to −0.48), and overall and reproductive health (mean attenuation −2.20; 95% CI: −4.18 to −0.21). Nonetheless, the EXT polygenic score remained nominally significant (two-sided P < 0.05) with 24 outcomes across the five categories, showing that the externalizing GWAS captures genetic effects that are not solely a consequence of uncontrolled population stratification, indirect genetic effects, or other forms of environmental confounding.
