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Associations of Circulating Biomarkers with Disease Risks: a Two-Sample Mendelian Randomization Study.
Elmas, Abdulkadir; Spehar, Kevin; Do, Ron; Castellano, Joseph M; Huang, Kuan-Lin.
Afiliación
  • Elmas A; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Spehar K; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Do R; Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Castellano JM; Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Huang KL; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
medRxiv ; 2024 Jul 01.
Article en En | MEDLINE | ID: mdl-39006413
ABSTRACT

Background:

Circulating biomarkers play a pivotal role in personalized medicine, offering potential for disease screening, prevention, and treatment. Despite established associations between numerous biomarkers and diseases, elucidating their causal relationships is challenging. Mendelian Randomization (MR) can address this issue by employing genetic instruments to discern causal links. Additionally, using multiple MR methods with overlapping results enhances the reliability of discovered relationships.

Methods:

Here we report an MR study using multiple methods, including inverse variance weighted, simple mode, weighted mode, weighted median, and MR Egger. We use the MR-base resource (v0.5.6)1 to evaluate causal relationships between 212 circulating biomarkers (curated from UK Biobank analyses by Neale lab and from Shin et al. 2014, Roederer et al. 2015, and Kettunen et al. 2016)2-4 and 99 complex diseases (curated from several consortia by MRC IEU and Biobank Japan).

Results:

We report novel causal relationships found by 4 or more MR methods between glucose and bipolar disorder (Mean Effect Size estimate across

methods:

0.39) and between cystatin C and bipolar disorder (Mean Effect Size -0.31). Based on agreement in 4 or more methods, we also identify previously known links between urate with gout and creatine with chronic kidney disease, as well as biomarkers that may be causal of cardiovascular conditions apolipoprotein B, cholesterol, LDL, lipoprotein A, and triglycerides in coronary heart disease, as well as lipoprotein A, LDL, cholesterol, and apolipoprotein B in myocardial infarction.

Conclusions:

This Mendelian Randomization study not only corroborates known causal relationships between circulating biomarkers and diseases but also uncovers two novel biomarkers associated with bipolar disorder that warrant further investigation. Our findings provide insight into understanding how biological processes reflecting circulating biomarkers and their associated effects may contribute to disease etiology, which can eventually help improve precision diagnostics and intervention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: MedRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos