Table 1.
Type I error rates for HIPO observed in datasets simulated under covariance structure estimated from studies of blood lipids.
See S1 Table 1a and 1b for detailed settings. Summary-level association statistics are simulated for 4 traits using genetic and phenotypic covariance matrices estimated from Global Lipids Genetics Consortium (GLGC) data, with and without population stratification. The results for HIPO-D1 and the most heritable trait are listed. Reported are the average of genome-wide type I error rates across 100 simulations, under significance thresholds p<0.05, p<0.01 and p<0.001.
Table 2.
Number of truly associated independent loci discovered by HIPO, MTAG and individual trait analysis observed in datasets simulated under the covariance structure estimated from studies of blood lipids.
See 1a-1d in S1 Table for detailed settings. We report the average number of truly associated loci identified by all the individual traits/HIPO components/MTAG estimates across 100 simulations, under significance threshold p < 5 × 10−8 and LD pruning threshold r2 < 0.1 and different loci required to be >0.5Mb apart.
Fig 1.
QQ plots for individual traits and underlying HIPO components across blood lipids, psychiatric diseases, social science traits.
Blood lipid traits include HDL, LDL, triglycerides (TG) and total cholesterol (TC). Psychiatric diseases include autism spectrum disorder (ASD), ADHD, bipolar disorder (BIP), major depressive disorder (MDD) and schizophrenia (SCZ). Meta-analysis QQ plot is also included for psychiatric diseases (in green). Social science traits include depressive symptoms (DS), neuroticism (NEU) and subjective well-being (SWB). Genomic control factors and average χ2 statistics are shown in the legend.
Table 3.
Novel loci discovered at genome-wide significance level (p < 5 × 10−8) by the first and second HIPO components of blood lipid traits.
Table 4.
Novel loci discovered at genome-wide significance level (p < 5 × 10−8) by HIPO-D1 for social science traits.
Table 5.
Evidence of replication of novel loci identified by HIPO analysis for social science traits in subsequent larger studies of DS and SWB.