WFRF:(Liu ZM)
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 03678naa a2200493 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:152055003 | |
| 003 | SwePub | |
| 008 | 240701s2023 | |||||||||||000 ||eng| | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1520550032 URI |
| 024 | 7 | a https://doi.org/10.1093/rheumatology/kead0542 DOI |
| 040 | a (SwePub)ki | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Zhang, L4 aut |
| 245 | 1 0 | a Using human genetics to understand the epidemiological association between obesity, serum urate, and gout |
| 264 | c 2023-02-03 | |
| 264 | 1 | b Oxford University Press (OUP),c 2023 |
| 520 | a ObjectivesWe aimed to clarify the genetic overlaps underlying obesity-related traits, serum urate, and gout.MethodsWe conducted a comprehensive genome-wide cross-trait analysis to identify genetic correlation, pleiotropic loci, and causal relationships between obesity (the exposure variable), gout (the primary outcome) and serum urate (the secondary outcome). Summary statistics were collected from the hitherto largest genome-wide association studies conducted for BMI (N = 806 834), waist-to-hip ratio (WHR; N = 697 734), WHR adjusted for BMI (WHRadjBMI; N = 694 649), serum urate (N = 288 649), and gout (Ncases = 13 179 and Ncontrols = 750 634).ResultsPositive overall genetic correlations were observed for BMI (rg = 0.27, P = 6.62 × 10−7), WHR (rg = 0.22, P = 6.26 × 10−7) and WHRadjBMI (rg = 0.07, P = 6.08 × 10−3) with gout. Partitioning the whole genome into 1703 LD (linkage disequilibrium)-independent regions, a significant local signal at 4q22 was identified for BMI and gout. The global and local shared genetic basis was further strengthened by the multiple pleiotropic loci identified in the cross-phenotype association study, multiple shared gene–tissue pairs observed by Transcriptome-wide association studies, as well as causal relationships demonstrated by Mendelian randomization [BMI–gout: OR (odds ratio) = 1.66, 95% CI = 1.45, 1.88; WHR–gout: OR = 1.57, 95% CI = 1.37, 1.81]. Replacing the binary disease status of gout with its latent pathological measure, serum urate, a similar pattern of correlation, pleiotropy and causality was observed with even more pronounced magnitude and significance.ConclusionOur comprehensive genome-wide cross-trait analysis demonstrates a shared genetic basis and pleiotropic loci, as well as a causal relationship between obesity, serum urate, and gout, highlighting an intrinsic link underlying these complex traits. | |
| 700 | 1 | a Zhang, WQ4 aut |
| 700 | 1 | a Xiao, CH4 aut |
| 700 | 1 | a Wu, XY4 aut |
| 700 | 1 | a Cui, HJ4 aut |
| 700 | 1 | a Yan, PJ4 aut |
| 700 | 1 | a Yang, C4 aut |
| 700 | 1 | a Tang, MS4 aut |
| 700 | 1 | a Wang, YT4 aut |
| 700 | 1 | a Chen, L4 aut |
| 700 | 1 | a Liu, YJ4 aut |
| 700 | 1 | a Zou, YQ4 aut |
| 700 | 1 | a Alfredsson, Lu Karolinska Institutet4 aut |
| 700 | 1 | a Klareskog, Lu Karolinska Institutet4 aut |
| 700 | 1 | a Yang, YF4 aut |
| 700 | 1 | a Yao, YQ4 aut |
| 700 | 1 | a Li, JY4 aut |
| 700 | 1 | a Liu, ZM4 aut |
| 700 | 1 | a Yang, CX4 aut |
| 700 | 1 | a Jiang, Xu Karolinska Institutet4 aut |
| 700 | 1 | a Zhang, B4 aut |
| 710 | 2 | a Karolinska Institutet4 org |
| 773 | 0 | t Rheumatology (Oxford, England)d : Oxford University Press (OUP)g 62:10, s. 3280-3290q 62:10<3280-3290x 1462-0332x 1462-0324 |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:152055003 |
| 856 | 4 8 | u https://doi.org/10.1093/rheumatology/kead054 |
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- Zhang, L
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- Yang, C
- Tang, MS
- Wang, YT
- Chen, L
- Liu, YJ
- Zou, YQ
- Alfredsson, L
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