PDF(Pubmed)
Abstract：
BACKGROUND: Epidemiological studies have revealed a significant association between impaired kidney function and certain mental disorders, particularly bipolar disorder (BIP) and major depressive disorder (MDD). However, the evidence regarding shared genetics and causality is limited due to residual confounding and reverse causation.
METHODS: In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium.
RESULTS: Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD.
CONCLUSIONS: In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted.
METHODS: In this study, we conducted a large-scale genome-wide cross-trait association study to investigate the genetic overlap between 5 kidney function biomarkers (eGFRcrea, eGFRcys, blood urea nitrogen (BUN), serum urate, and UACR) and 2 mental disorders (MDD, BIP). Summary-level data of European ancestry were extracted from UK Biobank, Chronic Kidney Disease Genetics Consortium, and Psychiatric Genomics Consortium.
RESULTS: Using LD score regression, we found moderate but significant genetic correlations between kidney function biomarker traits on BIP and MDD. Cross-trait meta-analysis identified 1 to 19 independent significant loci that were found shared among 10 pairs of 5 kidney function biomarkers traits and 2 mental disorders. Among them, 3 novel genes: SUFU, IBSP, and PTPRJ, were also identified in transcriptome-wide association study analysis (TWAS), most of which were observed in the nervous and digestive systems (FDR < 0.05). Pathway analysis showed the immune system could play a role between kidney function biomarkers and mental disorders. Bidirectional mendelian randomization analysis suggested a potential causal relationship of kidney function biomarkers on BIP and MDD.
CONCLUSIONS: In conclusion, the study demonstrated that both BIP and MDD shared genetic architecture with kidney function biomarkers, providing new insights into their genetic architectures and suggesting that larger GWASs are warranted.
摘要：
背景：流行病学研究揭示了肾功能受损与某些精神障碍之间的显著关联，尤其是双相情感障碍（BIP）和重度抑郁障碍（MDD）。然而,由于残余混杂和反向因果关系,关于共有遗传学和因果关系的证据是有限的.
方法：在本研究中，我们进行了一项大规模的全基因组交叉性状关联研究，以调查5种肾功能生物标志物之间的遗传重叠（eGFRcrea，eGFRcys,血尿素氮(BUN),血清尿酸，和UACR）和2种精神障碍（MDD，BIP）。欧洲血统的汇总数据来自英国生物银行，慢性肾脏病遗传学联盟,和精神病学基因组学联盟。
结果：使用LD评分回归，我们发现BIP和MDD的肾功能生物标志物性状之间存在中等但显著的遗传相关性.跨性状荟萃分析确定了1至19个独立的重要基因座，这些基因座在10对5个肾功能生物标志物性状和2个精神障碍中共享。其中,3个新基因：SUFU，IBSP,和PTPRJ,在全转录组关联研究分析(TWAS)中也得到了鉴定，其中大多数在神经系统和消化系统中观察到（FDR<0.05）。路径分析显示免疫系统可能在肾功能生物标志物和精神障碍之间发挥作用。双向孟德尔随机化分析提示肾功能生物标志物对BIP和MDD的潜在因果关系。
结论：结论：该研究表明，BIP和MDD与肾功能生物标志物共享遗传结构，为他们的基因结构提供新的见解，并建议有必要使用更大的GWAS。
方法：在本研究中，我们进行了一项大规模的全基因组交叉性状关联研究，以调查5种肾功能生物标志物之间的遗传重叠（eGFRcrea，eGFRcys,血尿素氮(BUN),血清尿酸，和UACR）和2种精神障碍（MDD，BIP）。欧洲血统的汇总数据来自英国生物银行，慢性肾脏病遗传学联盟,和精神病学基因组学联盟。
结果：使用LD评分回归，我们发现BIP和MDD的肾功能生物标志物性状之间存在中等但显著的遗传相关性.跨性状荟萃分析确定了1至19个独立的重要基因座，这些基因座在10对5个肾功能生物标志物性状和2个精神障碍中共享。其中,3个新基因：SUFU，IBSP,和PTPRJ,在全转录组关联研究分析(TWAS)中也得到了鉴定，其中大多数在神经系统和消化系统中观察到（FDR<0.05）。路径分析显示免疫系统可能在肾功能生物标志物和精神障碍之间发挥作用。双向孟德尔随机化分析提示肾功能生物标志物对BIP和MDD的潜在因果关系。
结论：结论：该研究表明，BIP和MDD与肾功能生物标志物共享遗传结构，为他们的基因结构提供新的见解，并建议有必要使用更大的GWAS。
