Fig. 4: Genetic correlation, partitioned heritability enrichment, and PRS prediction accuracy on multimodal brain age gaps.
From: The genetic architecture of multimodal human brain age
A Genetic correlation (gc) between GM, WM, and FC-BAG and 16 clinical traits. These traits include neurodegenerative diseases (e.g., AD) and their AI-derived subtypes (e.g., AD1 and AD24), neuropsychiatric disorders (e.g., ASD) and their subtypes (ASD1, 2, and 346), intelligence, and education. After adjusting for multiple comparisons using the FDR method, the * symbol denotes statistical significance (two-sided P value < 0.05). Supplementary table 3 and data 10 presents the sample size and P value. B The proportion of heritability enrichment for the 53 functional categories51. We only show the functional categories that survived the correction for multiple comparisons using the FDR method. C Cell type-specific partitioned heritability estimates. We included gene sets from Cahoy et al.104 for three main cell types (i.e., astrocyte, neuron, and oligodendrocyte). After adjusting for multiple comparisons using the FDR method, the * symbol denotes statistical significance (P value < 0.05). Detailed results, including P-values, are presented in Supplementary data 11. LDSC resulted in an empirical covariance matrix of coefficient estimates and tested whether the per-SNP heritability is greater in the category/cell type than out of the category/cell type (i.e., one-sided). For Figure (A–C), data are presented as the mean value of the estimated parameters and error bars representing the standard error of the estimated parameters. D The incremental R2 of the PRS derived by PRC-CS to predict the GM, WM, and FC-BAG in the target/test data (i.e., the split2 GWAS). The y-axis indicates the proportions of phenotypic variation (GM, WM, and FC-BAG) that the PRS can significantly and additionally explain. The x-axis lists the seven P value thresholds considered. Abbreviation: AD Alzheimer’s disease, ADHD attention-deficit/hyperactivity disorder, ASD autism spectrum disorder, BIP bipolar disorder, MDD major depressive disorder, OCD obsessive-compulsive disorder, SCZ schizophrenia.
