Evidence supports a causal association between allele-specific vitamin D receptor binding and multiple sclerosis among Europeans

骨化三醇受体 孟德尔随机化 等位基因 维生素D与神经学 维生素D结合蛋白 基因座(遗传学) 遗传学 遗传关联 生物 内科学 内分泌学 单核苷酸多态性 医学 基因 基因型 遗传变异
作者
Crawford W. Adams,Ali Manouchehrinia,Hong Quach,Diana Quach,Tomas Olsson,Ingrid Kockum,Catherine Schaefer,Chris P. Ponting,Lars Alfredsson,Lisa F. Barcellos
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [National Academy of Sciences]
卷期号:121 (8)
标识
DOI:10.1073/pnas.2302259121
摘要

Although evidence exists for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels, and multiple sclerosis (MS), the role of variation in vitamin D receptor (VDR) binding in MS is unknown. Here, we leveraged previously identified variants associated with allele imbalance in VDR binding (VDR-binding variant; VDR-BV) in ChIP-exo data from calcitriol-stimulated lymphoblastoid cell lines and 25(OH)D serum levels from genome-wide association studies to construct genetic instrumental variables (GIVs). GIVs are composed of one or more genetic variants that serve as proxies for exposures of interest. Here, GIVs for both VDR-BVs and 25(OH)D were used in a two-sample Mendelian Randomization study to investigate the relationship between VDR binding at a locus, 25(OH)D serum levels, and MS risk. Data for 13,598 MS cases and 38,887 controls of European ancestry from Kaiser Permanente Northern California, Swedish MS studies, and the UK Biobank were included. We estimated the association between each VDR-BV GIV and MS. Significant interaction between a VDR-BV GIV and a GIV for serum 25OH(D) was evidence for a causal association between VDR-BVs and MS unbiased by pleiotropy. We observed evidence for associations between two VDR-BVs (rs2881514, rs2531804) and MS after correction for multiple tests. There was evidence of interaction between rs2881514 and a 25(OH)D GIV, providing evidence of a causal association between rs2881514 and MS. This study is the first to demonstrate evidence that variation in VDR binding at a locus contributes to MS risk. Our results are relevant to other autoimmune diseases in which vitamin D plays a role.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
英俊白莲发布了新的文献求助10
1秒前
OMR123完成签到,获得积分10
2秒前
西瓜完成签到,获得积分10
2秒前
2秒前
2秒前
yuC发布了新的文献求助30
3秒前
科研通AI5应助左肩微笑采纳,获得10
3秒前
4秒前
4秒前
辛某发布了新的文献求助10
4秒前
吴军霄完成签到,获得积分10
5秒前
6秒前
豆豆完成签到 ,获得积分10
7秒前
展希希发布了新的文献求助10
7秒前
万能图书馆应助缥缈冬寒采纳,获得10
7秒前
vv发布了新的文献求助10
8秒前
汉堡包应助chiweiyoung采纳,获得10
8秒前
10秒前
11秒前
一支布洛芬完成签到,获得积分20
11秒前
11秒前
香蕉觅云应助英俊白莲采纳,获得10
11秒前
英俊的铭应助树精采纳,获得10
13秒前
Ava应助yummy采纳,获得10
13秒前
YJ888发布了新的文献求助10
13秒前
可爱的函函应助lzx采纳,获得10
15秒前
15秒前
gulllluuuukk完成签到,获得积分10
17秒前
Lynn怯霜静完成签到,获得积分10
18秒前
科研通AI5应助青青子衿采纳,获得10
19秒前
孙燕应助lalala采纳,获得50
19秒前
20秒前
20秒前
斯文念波发布了新的文献求助10
21秒前
24秒前
辛某完成签到,获得积分10
24秒前
香蕉觅云应助期刊采纳,获得50
25秒前
25秒前
25秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989550
求助须知:如何正确求助?哪些是违规求助? 3531774
关于积分的说明 11254747
捐赠科研通 3270278
什么是DOI,文献DOI怎么找? 1804966
邀请新用户注册赠送积分活动 882125
科研通“疑难数据库(出版商)”最低求助积分说明 809176