Scientific Research and Experiment Center, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, People's Republic of China.
Ann Hum Genet. 2022 May;86(3):127-136. doi: 10.1111/ahg.12457. Epub 2022 Jan 10.
Rheumatoid arthritis (RA) is a complex disease with several risk factors. The effects of blood metabolites on RA remains elusive. We conducted a genetic correlation scan to explore the relevance of blood metabolism with RA.
The genome-wide association study (GWAS) dataset of RA(2014) was obtained from a large scale meta-analysis, including 29,880 RA cases and 73,758 controls. The GWAS datasets of 529 blood metabolites were derived from a recently published study. Linkage disequilibrium score regression (LDSC) analysis was performed to evaluate the genetic correlation between each of the blood metabolite and RA(2014). Then we used another GWAS data of RA(2021) and blood metabolites for LDSC analysis to verify whether the same blood metabolites were genetically correlated with RA. Mendelian randomization (MR) analysis was then applied to assess the causal relationship between the significant blood metabolites identified by LDSC and RA(2014).
Six suggestive blood metabolites were identified for RA(2014), including 10-Undecenoate (correlation coefficient = -0.1686, p value = 0.0394), isovalerylcarnitine (correlation coefficient = 0.1660 p value = 0.0273), proline (correlation coefficient = 0.1647, p value = 0.0145), pantothenate (correlation coefficient = -0.3311, p value = 0.0078), tyrosine (correlation coefficient = 0.1735, p value = 0.0010), X-14057 (correlation coefficient = 0.2695, p value = 0.0373). We identified four blood metabolites may have genetic correlations with RA(2021), including oleoylcarnitine (correlation coefficient = 0.1927, p value = 0.0432), levulinate (correlation coefficient = 0.1008, p value = 0.0413), pantothenate (correlation coefficient = -0.2311, p value = 0.0180), tyrosine (correlation coefficient = 0.1301, p value = 0.0078). There are two identical blood metabolites were found to be related with RA: pantothenate and tyrosine. It was found that there was a significant positive causal relationship between RA (exposure) and 10-Undecenoate (outcome) (β = 0.0077, SE = 0.0033, p = 0.0192) by MR analysis.
We investigated the genetic correlation and causal relationship between RA and blood metabolites by LDSC and MR analysis. These results may provide novel insights into the genetic mechanism of RA.
类风湿关节炎（RA）是一种具有多种风险因素的复杂疾病。血液代谢物对 RA 的影响仍不清楚。我们进行了遗传相关扫描，以探讨血液代谢与 RA 的相关性。
从一项大型荟萃分析中获得了 RA（2014 年）的全基因组关联研究（GWAS）数据集，其中包括 29880 例 RA 病例和 73758 例对照。最近发表的一项研究中得出了 529 种血液代谢物的 GWAS 数据集。采用连锁不平衡评分回归（LDSC）分析评估每个血液代谢物与 RA（2014 年）之间的遗传相关性。然后，我们使用另一个 RA（2021 年）和血液代谢物的 GWAS 数据进行 LDSC 分析，以验证相同的血液代谢物是否与 RA 存在遗传相关性。然后应用孟德尔随机化（MR）分析来评估通过 LDSC 确定的与 RA（2014 年）显著相关的血液代谢物之间的因果关系。
确定了 6 种与 RA（2014 年）相关的提示性血液代谢物，包括 10-十一烯酸（相关系数=-0.1686，p 值=0.0394）、异戊酰肉碱（相关系数=0.1660，p 值=0.0273）、脯氨酸（相关系数=0.1647，p 值=0.0145）、泛酸（相关系数=-0.3311，p 值=0.0078）、酪氨酸（相关系数=0.1735，p 值=0.0010）、X-14057（相关系数=0.2695，p 值=0.0373）。我们确定了四种可能与 RA（2021 年）具有遗传相关性的血液代谢物，包括油酰肉碱（相关系数=0.1927，p 值=0.0432）、戊烯酸（相关系数=0.1008，p 值=0.0413）、泛酸（相关系数=-0.2311，p 值=0.0180）、酪氨酸（相关系数=0.1301，p 值=0.0078）。发现了两种与 RA 相关的相同血液代谢物：泛酸和酪氨酸。通过 MR 分析发现，RA（暴露）与 10-十一烯酸（结局）之间存在显著正因果关系（β=0.0077，SE=0.0033，p=0.0192）。
我们通过 LDSC 和 MR 分析研究了 RA 与血液代谢物之间的遗传相关性和因果关系。这些结果可能为 RA 的遗传机制提供新的见解。
