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Human fetal brain expression SNP-weights for use in TWAS

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posted on 2020-04-03, 13:28 authored by Nick BrayNick Bray, Oliver Pain

Single nucleotide polymorphism (SNP)-weights for Ensembl gene and transcript-level expression were derived from genotyping and RNA sequencing data from 120 human fetal brains aged 12 – 19 post-conception weeks. Prior to deriving SNP-weights, gene- and transcript-level expression data were normalized and adjusted for sex, age, RIN, sequencing batch, 3 genotype principal components and 10 PEER factors. For a full description of the sample and data generation, please see: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1567-1

Expression weights for use in transcriptome-wide association studies (TWAS) were derived using FUSION software (http://gusevlab.org/projects/fusion/#computing-your-own-functional-weights). SNP-weights were only generated for genes and transcripts with significant evidence of cis-heritable expression at the default P-value (P < 0.01) in FUSION (1351 Ensembl genes and 3985 Ensembl transcripts). Note that the number of genes that will be testable by TWAS may differ as this will depend on the number of overlapping SNPs between the weights files and the GWAS summary statistics.

Expression weights were derived using only SNPs available in the FUSION LD reference (HapMap3 SNPs), in line with the FUSION protocol. Expression weights provided here are in the same format as weights downloaded from the FUSION website.

Use of these expression weights to perform TWAS of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, bipolar disorder, major depressive disorder and schizophrenia are described in Hall et al. 'Cis-effects on gene expression in the human prenatal brain associated with genetic risk for neuropsychiatric disorders' Molecular Psychiatry (in press).


Files:

- Ensembl gene level weights: op-fusion-fetal_brain-full_sample-gene_level.tar.gz

- Ensembl transcript level weights: op-fusion-fetal_brain-full_sample-transcript_level.tar.gz



Funding

This work was supported by Medical Research Council (U.K.) project grants (MR/L010674/1 and MR/L010674/2) and Centre grant (MR/L010305/1).

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