Genetic and functional analysis of Raynaud’s syndrome implicates loci in vasculature and immunity

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 signa..., 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)., , # 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 summ...

雷诺综合征（Raynaud’s syndrome）是一种自主神经功能障碍（dysautonomia），暴露于寒冷环境会引发血管收缩与缺氧，尤其多见于四肢末端。我们对四个队列开展元分析，发现八个基因座（ADRA2A、IRX1、NOS3、ACVR2A、TMEM51、PCDH10-DT、HLA、RAB6C），其中ADRA2A、ACVR2A、NOS3、TMEM51与IRX1与表达数量性状基因座（eQTLs）共定位，尤其在远端动脉中。CRISPR基因编辑进一步显示，ADRA2A与NOS3基因座可调控基因表达；原位RNA scope则阐明了ADRA2A在小血管中的特异性，以及IRX1在皮肤毛细血管周围的分布特征。寒冷环境下的功能收缩实验表明，缺乏ADRA2A的平滑肌细胞收缩能力较低，而过表达ADRA2A的平滑肌细胞收缩能力较高。总体而言，我们的研究凸显了结合功能随访的全基因组关联测试作为解析复杂疾病方法的潜力。研究结果表明，通过ADRA2A的温度依赖性肾上腺素能信号通路、IRX1对微血管的作用、内皮信号……本数据集包含雷诺综合征元分析的汇总统计数据，该元分析基于四个独立人群队列的全基因组关联研究（GWAS）汇总统计数据开展：英国生物银行（The UK Biobank）、芬兰基因组数据库第10版（FinnGen data freeze 10）、爱沙尼亚生物银行（The Estonian Biobank）与麻省总医院布莱根妇女医院生物银行（The Mass-General Brigham Biobank）。各队列所用表型及开展的GWAS详情可参见相关出版物。元分析采用METAL工具（https://genome.sph.umich.edu/wiki/METAL_Documentation）并使用标准设置开展，最终汇总统计数据以GRCh38版本呈现（详情参见相关出版物）。

# 雷诺综合征的遗传与功能分析揭示血管与免疫相关基因座

[https://doi.org/10.5061/dryad.1g1jwsv53](https://doi.org/10.5061/dryad.1g1jwsv53)

本数据集包含雷诺综合征元分析的汇总统计数据，该元分析基于四个独立人群队列的全基因组关联研究（GWAS）汇总统计数据开展：英国生物银行（The UK Biobank）、芬兰基因组数据库第10版（FinnGen data freeze 10）、爱沙尼亚生物银行（The Estonian Biobank）与麻省总医院布莱根妇女医院生物银行（The Mass-General Brigham Biobank）。各队列所用表型及开展的GWAS详情可参见相关出版物。元分析采用METAL工具（https://genome.sph.umich.edu/wiki/METAL_Documentation）并使用标准设置开展，最终汇总统计数据以GRCh38版本呈现（详情参见相关出版物：https://doi.org/10.1016/j.xgen.2024.100630）。

## 数据与文件结构描述

汇总……