DOI: 10.5281/zenodo.15860712
title: SingleBrain: Single-nucleus Disease/Sex Specific Expression QTL Meta-analysis Summary Statistics across Multiple Human Brain Cohorts

description: https://github.com/RajLabMSSM/SingleBrain

Full associations and top association summary statistics for disease/sex-specific QTLs mapped in a meta-analysis across multiple human brain single-nucleus RNA seq cohorts, as part of the "SingleBrain" project.

Sample size = 983 European ancestry donors from 757 unique donors

4 cohorts (Fujita et al., Mathys et al., Bryois et al., Gabitto et al.) meta-analyzed using the linear mixed model random-effects meta-analysis software mmQTL (PMID: 35058635).

Each file has the following naming convention:

{Cell type}_{Trait}_eqtl_{ASSOC}.tsv.gz

References

The following reference was used for mapping phenotypes:

1. GENCODE - GENCODE v38 comprehensive transcripts (https://www.gencodegenes.org/human/release_38.html)

Cell type

The following brain 7 major cell types and 28 subtypes were tested for genetic association:



Ast: astrocytes

End: endothelial cells

Ext: excitatory neurons

IN: inhibitory neurons

MG: microglia

OD: oligodendrocytes

OPC: oligodendrocyte progenitor cell


Each subtype has numbers appended after cell names.



MiGA3: A meta-analysis that integrated data from the isoMiGA(https://zenodo.org/records/8250771)


All phenotype matrices were scaled and centered and then quantile normalized.

Trait



male: male donors (n=404)  

female: female donors (n=579)

disease: AD and MCI donors (n=543)

control: Healthy control donors (n=342)


Associations

Top associations (top_assoc.tsv.gz) list the SNP-feature pair with the lowest adjusted P-value (qval) for that feature.

Full associations (full_assoc.tsv.gz) list all tested SNP-feature pairs.

Data dictionary

The columns of the two association files only differ by the presence of the qval column in the top associations.

feature: the phenotype being tested

variant_id: the genetic variant being tested

chr: chromosome

pos: position (hg38)

ref: reference allele

alt: alternate allele

Allele: the effect allele that the beta is relative to

beta_tissue_0: Fujita et al. cohort beta

sd_tissue_0: Fujita et al. cohort standard error

z_tissue_0: Fujita et al. cohort Z-score

beta_tissue_1: Mathys et al. cohort beta

sd_tissue_1: Mathys et al. cohort standard error

z_tissue_1: Mathys et al. cohort Z-score

beta_tissue_2: Gabitto et al. cohort beta

sd_tissue_2: Gabitto et al. cohort standard error

z_tissue_2: Gabitto et al. cohort Z-score

beta_tissue_3: Bryois et al. cohort beta

sd_tissue_3: Bryois et al. cohort standard error

z_tissue_3: Bryois et al. cohort Z-score

fixed_beta: Fixed effect meta-analysis estimate of the beta

fixed_sd: Fixed effect meta-analysis standard error of the beta

fixed_z: Fixed effect meta-analysis Z-score

Random_Z: Random effect meta-analysis Z-score

Fixed_P: Fixed effect meta-analysis P-value

Random_P: Random effect meta-analysis P-value

Fixed_bonf:  Fixed effect meta-analysis P-value adjusted for the number of variants tested in that feature (Bonferroni)

Random_bonf: Random effect meta-analysis P-value adjusted for the number of variants tested in that feature (Bonferroni)

Fixed_FDR: Fixed effect meta-analysis P-value adjusted for the number of variants tested in that feature (FDR)

Random_FDR: Random effect meta-analysis P-value adjusted for the number of variants tested in that feature (FDR)

qval: Random effect meta-analysis P-value adjusted for the number of variants tested in that feature (FDR) and for the number of features tested in the dataset (Storey's q value)