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. Author manuscript; available in PMC: 2025 Dec 1.
Published in final edited form as: Nat Genet. 2024 Nov 11;56(12):2672–2684. doi: 10.1038/s41588-024-01972-8

Fig. 2: Cerebrospinal fluid pQTLs are consistent across disease and largely tissue and molecule-specific.

Fig. 2:

a. Combined Manhattan plot of the pQTL associations identified from linear regression analysis of 3,506 CSF samples and 7,008 aptamers. X-axis: genome position of an associated variant; y-axis: −log10(p-value) for association of each SNP with an aptamer. b. 2D Manhattan plot of 2,477 index pQTLs for 2,042 aptamers that were significant in the joint analysis. X-axis: genome position of the pQTL signal; y-axis: location of the protein-coding gene corresponding to the aptamer with a pQTL. Color represents cis or trans status of the index variant (cis, blue; trans, green). The top panel maps the pleiotropic regions of the genome (limited to 100 proteins with an association in the same region). c. Scatter plot of index pQTL variant absolute effect size (y-axis) vs effect allele frequency (x-axis). Color represents cis or trans status of the index variant (cis, blue; trans, green). Correlation was calculated using the Pearson method with two-sided P-values (cis P=1.36×10−73, trans P=2.97×10−115). d. Scatter plot of cis index pQTL −log10(P) (y-axis) vs distance from the transcription start site of the gene encoding the associated protein (x-axis). Color represents the minor allele frequency (darker=less common). e. Scatter plot of effect size of index pQTL variants in dichotomized amyloid/tau positive samples (x-axis) vs dichotomized amyloid/tau negative samples (y-axis). Color represents minor allele frequency (darker=less common). Correlation was calculated using the Pearson method with two-sided P estimated to be below the underflow value. f. Colocalization of CSF pQTL associations with plasma pQTL associations from Ferkingstad et al11. Plasma + CSF: pQTL associations that colocalized across tissues. CSF-specific: pQTL associations that did not colocalize with plasma pQTLs for the same protein. New Proteins: pQTL associations for proteins measured in CSF but not plasma. Color represents cis or trans status of the index CSF pQTL (cis, blue; trans, green). g. Colocalization of cis CSF pQTL associations with various QTL types. Green bars represent brain-relevant tissues, while blue bars represent other tissues. Bar labels represent the number of colocalizing QTLs.