PDF(Pubmed)
Abstract：
UNASSIGNED: Sarcoidosis has been considered to be associated with many autoimmune diseases (ADs), but the cause-and-effect relationship between these two diseases has not been fully explored. Therefore, the objective of this study is to explore the possible genetic association between sarcoidosis and ADs.
UNASSIGNED: We conducted a bidirectional Mendelian randomization (MR) study using genetic variants associated with ADs and sarcoidosis (4,041 cases and 371,255 controls) from the FinnGen study. The ADs dataset comprised 96,150 cases and 281,127 controls, encompassing 44 distinct types of autoimmune-related diseases. Subsequently, we identified seven diseases within the ADs dataset with a case size exceeding 3,500 and performed subgroup analyses on these specific diseases.
UNASSIGNED: The MR evidence supported the causal association of genetic predictors of ADs with an increased risk of sarcoidosis (OR = 1.79, 95% CI = 1.59 to 2.02, P IVW-FE = 1.01 × 10-21), and no reverse causation (OR = 1.05, 95% CI 0.99 to 1.12, P IVW-MRE = 9.88 × 10-2). Furthermore, subgroup analyses indicated that genetic predictors of type 1 diabetes mellitus (T1DM), celiac disease, and inflammatory bowel disease (IBD) were causally linked to an elevated risk of sarcoidosis (All P < 6.25 × 10-3). Conversely, genetic predictors of sarcoidosis showed causal associations with a higher risk of type 1 diabetes mellitus (P < 6.25 × 10-3).
UNASSIGNED: The present study established a positive causal relationship between genetic predictors of ADs (e.g. T1DM, celiac disease, and IBD) and the risk of sarcoidosis, with no evidence of reverse causation.
UNASSIGNED: We conducted a bidirectional Mendelian randomization (MR) study using genetic variants associated with ADs and sarcoidosis (4,041 cases and 371,255 controls) from the FinnGen study. The ADs dataset comprised 96,150 cases and 281,127 controls, encompassing 44 distinct types of autoimmune-related diseases. Subsequently, we identified seven diseases within the ADs dataset with a case size exceeding 3,500 and performed subgroup analyses on these specific diseases.
UNASSIGNED: The MR evidence supported the causal association of genetic predictors of ADs with an increased risk of sarcoidosis (OR = 1.79, 95% CI = 1.59 to 2.02, P IVW-FE = 1.01 × 10-21), and no reverse causation (OR = 1.05, 95% CI 0.99 to 1.12, P IVW-MRE = 9.88 × 10-2). Furthermore, subgroup analyses indicated that genetic predictors of type 1 diabetes mellitus (T1DM), celiac disease, and inflammatory bowel disease (IBD) were causally linked to an elevated risk of sarcoidosis (All P < 6.25 × 10-3). Conversely, genetic predictors of sarcoidosis showed causal associations with a higher risk of type 1 diabetes mellitus (P < 6.25 × 10-3).
UNASSIGNED: The present study established a positive causal relationship between genetic predictors of ADs (e.g. T1DM, celiac disease, and IBD) and the risk of sarcoidosis, with no evidence of reverse causation.
摘要：
■结节病被认为与许多自身免疫性疾病（AD）有关，但是这两种疾病之间的因果关系尚未得到充分探索。因此,本研究的目的是探讨结节病与ADs之间可能的遗传关联.
■我们使用FinnGen研究中与AD和结节病相关的遗传变异（4,041例和371,255例对照）进行了一项双向孟德尔随机化（MR）研究。AD数据集包括96,150例病例和281,127例对照，包括44种不同类型的自身免疫相关疾病。随后，我们在AD数据集中确定了7种病例数超过3,500的疾病,并对这些特定疾病进行了亚组分析.
■MR证据支持AD的遗传预测因子与结节病风险增加的因果关系（OR=1.79，95％CI=1.59至2.02，PIVW-FE=1.01×10-21），无反向因果关系(OR=1.05，95%CI0.99~1.12，PIVW-MRE=9.88×10-2)。此外，亚组分析表明，1型糖尿病（T1DM）的遗传预测因子，乳糜泻,和炎症性肠病（IBD）与结节病风险升高有因果关系（所有P<6.25×10-3）。相反，结节病的遗传预测因子显示与1型糖尿病的高风险有因果关系(P<6.25×10-3).
■本研究建立了AD的遗传预测因子之间的正因果关系（例如T1DM，乳糜泻,和IBD)和结节病的风险，没有反向因果关系的证据。
■我们使用FinnGen研究中与AD和结节病相关的遗传变异（4,041例和371,255例对照）进行了一项双向孟德尔随机化（MR）研究。AD数据集包括96,150例病例和281,127例对照，包括44种不同类型的自身免疫相关疾病。随后，我们在AD数据集中确定了7种病例数超过3,500的疾病,并对这些特定疾病进行了亚组分析.
■MR证据支持AD的遗传预测因子与结节病风险增加的因果关系（OR=1.79，95％CI=1.59至2.02，PIVW-FE=1.01×10-21），无反向因果关系(OR=1.05，95%CI0.99~1.12，PIVW-MRE=9.88×10-2)。此外，亚组分析表明，1型糖尿病（T1DM）的遗传预测因子，乳糜泻,和炎症性肠病（IBD）与结节病风险升高有因果关系（所有P<6.25×10-3）。相反，结节病的遗传预测因子显示与1型糖尿病的高风险有因果关系(P<6.25×10-3).
■本研究建立了AD的遗传预测因子之间的正因果关系（例如T1DM，乳糜泻,和IBD)和结节病的风险，没有反向因果关系的证据。
