DOI: 10.5061/dryad.1g1jwsv53
title: Genetic and functional analysis of Raynaud’s syndrome implicates loci in vasculature and immunity

description: Raynaud’s syndrome is a dysautonomia where exposure to cold causes
 vasoconstriction and hypoxia, particularly in the extremities. We
 performed meta-analysis in four cohorts discovering eight loci (ADRA2A,
 IRX1, NOS3, ACVR2A, TMEM51, PCDH10-DT, HLA, RAB6C) where ADRA2A, ACVR2A,
 NOS3, TMEM51 and IRX1 colocalized with eQTLs, particularly in distal
 arteries. CRISPR gene editing further showed that ADRA2A and NOS3 loci
 modified gene expression and in situ RNA scope clarified the specificity
 of ADRA2A in small vessels, and IRX1 around small capillaries in the skin.
 Functional contraction assay in cold showed lower contraction in
 ADRA2A-deficient and higher contraction in ADRA2A-overexpressing smooth
 muscle cells. Overall, our study highlights the power of genome-wide
 association testing with functional follow-up as a method to understand
 complex diseases. The results indicate temperature dependent adrenergic
 signaling through ADRA2A, effects at the microvasculature by IRX1,
 endothelial signaling by NOS3 and immune mechanisms by the HLA locus in
 Raynaud’s syndrome.
description: This dataset includes summary statistics from Raynaud's
 syndrome meta-analysis conducted from GWAS summary statistics of four
 independent population cohorts: The UK Biobank, FinnGen data freeze 10,
 The Estonian Biobank and The Mass-General Brigham Biobank. Details of the
 phenotype used and the GWAS performed in the individual cohorts can be
 found from the corresponding publication. The meta-analysis was conducted
 using METAL (https://genome.sph.umich.edu/wiki/METAL_Documentation) with the standard settings and the final summary statistics are displayed in GRCh38 (for further details, see the corresponding publication).
description: # Genetic and Functional Analysis of Raynaud's Syndrome Implicates
 Loci in Vasculature and Immunity
 [https://doi.org/10.5061/dryad.1g1jwsv53](https://doi.org/10.5061/dryad.1g1jwsv53) This dataset includes summary statistics from Raynaud's syndrome meta-analysis conducted from GWAS (genome-wide association study) summary statistics of four independent population cohorts: The UK Biobank, FinnGen data freeze 10, The Estonian Biobank and The Mass-General Brigham Biobank. Details of the phenotype used and the GWAS performed in the individual cohorts can be found from the corresponding publication. The meta-analysis was conducted using METAL ([https://genome.sph.umich.edu/wiki/METAL_Documentation](https://genome.sph.umich.edu/wiki/METAL_Documentation)) with the standard settings and the final summary statistics are displayed in GRCh38 (for further details, see the corresponding publication https://doi.org/10.1016/j.xgen.2024.100630).  ## Description of the data and file structure The summary statistics include the following columns:  * rsID - identification for the single-nucleotide variant * CHR - Chromosome * POS - Genomic position in GRCh38  * Alt - Alternative allele (the effect allele) * Ref - Reference allele  * AF_Alt - Combined allele frequency of the alternative allele from all the cohorts used  * Effect - The estimate of effect size (beta) * StdErr - Standard error of the beta * Pval - P-value of the association * HetPVal - Heterogeneity P-value reflecting the variation in study outcomes between studies (P &lt; 0.05 implies heterogeneity) * N - total number of individuals in the meta-analysis ## Sharing/Access information Data was derived from the following sources: The UK Biobank, FinnGen, The Estonian Biobank and The Mass-General Brigham Biobank.  The FinnGen individual level data may be accessed through applications to the Finnish Biobanks’ FinnBB portal, Fingenious ([www.finbb.fi](http://www.finbb.fi)). For the individual level data of the UKB, applications can be made through the UKB portal at [https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access](https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access). For the Mass-General Brigham Biobank, individual level data are available from the Mass General Brigham Human Research Office/Institutional Review Board at Mass General Brigham (contact located at [https://www.partners.org/Medical-Research/Support-Offices/Human-Research-Committee-IRB/Default.aspx](https://www.partners.org/Medical-Research/Support-Offices/Human-Research-Committee-IRB/Default.aspx)) for researchers who meet the criteria for access to confidential data. Lastly, for the Estonian Biobank, preliminary inquiries to access individual level data for scientific research can be sent to [releases@ut.ee](mailto:releases@ut.ee). ## Code/Software GWAS in each individual cohort was conducted using REGENIE ([https://rgcgithub.github.io/regenie/](https://rgcgithub.github.io/regenie/)) and the meta-analysis was conducted using METAL ([https://genome.sph.umich.edu/wiki/METAL_Documentation](https://genome.sph.umich.edu/wiki/METAL_Documentation)) (for further details, see the corresponding publication).