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October 24, 2022Open Access

GWAS of circulating metabolic traits identifies >400 independent loci, revealing substantial pleiotropy and novel pathways.

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Why the study?

Detailed knowledge of the genetic determinants of systemic metabolism is pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases.

Population

Up to 136,016 participants from 33 predominantly population-based cohorts

Design

Genome-wide association study meta-analysis

Key result

A genome-wide association meta-analysis of 233 circulating metabolic traits in up to 136,016 participants identified over 400 independent loci, revealing substantial pleiotropy and novel pathways.

Authors

MKMinna K. KarjalainenSKSavita KarthikeyanCOClare Oliver‐Williams

Discussion

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Overview

Extends the genetic map of 233 metabolites in large cohorts; leaves open causal links to cardiovascular disease.

Study Design

Type

Meta-Analysis (n=136,016)

Multicenter

Yes

Structured PICO

P
Population
Up to 136,016 participants from 33 predominantly population-based cohorts with NMR metabolomics data for 233 circulating metabolic traits.
O
Outcome
233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy (213 lipid and lipoprotein parameters or fatty acids, and 20 non-lipid traits)surrogate

Main Result

p-value: p=< 5 × 10-8

This large-scale genome-wide association study of 233 circulating metabolic traits identified over 400 independent loci, revealing substantial genetic pleiotropy and novel pathways linking metabolism to complex diseases.

Limitations

  • Differences in sample type (EDTA plasma vs serum) and fasting status between cohorts can significantly impact genetic associations.
  • Pervasive genetic pleiotropy can bias Mendelian randomization analyses if instrument variants are not carefully selected.

Cite This Study

Karjalainen et al. (2022) conducted a meta-analysis in Circulating metabolic traits (n=136,016). Genetic variants (SNPs) vs. Reference alleles was evaluated on Genome-wide significant associations with 233 metabolic traits (p=< 5 × 10-8). A genome-wide association meta-analysis of 233 circulating metabolic traits in up to 136,016 participants identified over 400 independent loci, revealing substantial pleiotropy and novel pathways.

synapsesocial.com/papers/6aaba1fd3ca19a177bd3b8a7https://doi.org/10.1101/2022.10.20.22281089
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Genome-wide characterization of circulating metabolic biomarkers2024 · 269 citations
  2. 2Cross-platform genetic discovery of small molecule products of metabolism and application to clinical outcomes2020 · 16 citations
  3. 3Genetic Architecture and Analysis Practices of Circulating Metabolites in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program2024 · 2 citations
  4. 4Pleiotropic and sex-specific genetic architecture of circulating metabolic markers2024 · 2 citations
  5. 5Genetic analysis of circulating metabolic traits in 619,372 individuals2026 · 3 citations