Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Sci Rep. 2023 Apr 11;13(1):5852. doi: 10.1038/s41598-023-32799-8.
Some autoimmune (AI) conditions affect white blood cell (WBC) counts. Whether a genetic predisposition to AI disease associates with WBC counts in populations expected to have low numbers of AI cases is not known. We developed genetic instruments for 7 AI diseases using genome-wide association study summary statistics. Two-sample inverse variance weighted regression (IVWR) was used to determine associations between each instrument and WBC counts. Effect size represents change in transformed WBC counts per change in log odds-ratio of the disease. For AI diseases with significant associations by IVWR, polygenic risk scores (PRS) were used to test for associations with measured WBC counts in individuals of European ancestry in a community-based (ARIC, n = 8926), and a medical-center derived cohort (BioVU, n = 40,461). The IVWR analyses revealed significant associations between 3 AI diseases and WBC counts: systemic lupus erythematous (Beta = - 0.05 [95% CI, - 0.06, - 0.03]), multiple sclerosis (Beta = - 0.06 [- 0.10, - 0.03]), and rheumatoid arthritis (Beta = 0.02 [0.01, 0.03]). PRS for these diseases showed associations with measured WBC counts in ARIC and BioVU. Effect sizes tended to be larger among females, consistent with the known higher prevalence of these diseases among this group. This study shows that genetic predisposition to systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis was associated with WBC counts, even in populations expected to have very low numbers of disease cases.
一些自身免疫（AI）疾病会影响白细胞（WBC）计数。在预计 AI 病例数量较少的人群中，是否存在 AI 疾病的遗传易感性与 WBC 计数相关尚不清楚。我们使用全基因组关联研究汇总统计数据为 7 种 AI 疾病开发了遗传工具。两样本逆方差加权回归（IVWR）用于确定每个工具与 WBC 计数之间的关联。效应大小代表疾病的对数优势比每变化一个单位时，WBC 计数的变化量。对于通过 IVWR 分析具有显著关联的 AI 疾病，多基因风险评分（PRS）用于测试欧洲裔个体中与测量的 WBC 计数的关联，这些个体来自社区（ARIC，n = 8926）和医疗中心衍生队列（BioVU，n = 40461）。IVWR 分析显示，3 种 AI 疾病与 WBC 计数之间存在显著关联：系统性红斑狼疮（Beta = -0.05 [95% CI，-0.06，-0.03]）、多发性硬化症（Beta = -0.06 [-0.10，-0.03]）和类风湿关节炎（Beta = 0.02 [0.01，0.03]）。这些疾病的 PRS 与 ARIC 和 BioVU 中测量的 WBC 计数相关。在女性中，效应大小往往更大，这与该群体中这些疾病的更高患病率一致。这项研究表明，系统性红斑狼疮、类风湿关节炎和多发性硬化症的遗传易感性与 WBC 计数相关，即使在预计 AI 病例数量非常少的人群中也是如此。
