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Updated: Mar 3, 2026
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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Platform-dependent effects of genetic variants on plasma APOL1
Qingbo S Wang1, Jinguo Huang1, Leanne J G Chan1
1Calico Life Sciences LLC, South San Francisco, CA, USA.
Iscience
|March 2, 2026
Summary
Genetic variations in apolipoprotein L1 (APOL1) influence kidney disease risk. Different proteomic methods yield conflicting results for APOL1 levels, suggesting conformational changes affecting detection.
Area of Science:
- Genetics
- Proteomics
- Nephrology
Background:
- Apolipoprotein L1 (APOL1) gene variants are linked to kidney disease in individuals of African ancestry.
- Understanding APOL1's role requires analyzing its circulating levels and genetic influences.
Purpose of the Study:
- To investigate the genetic drivers of circulating APOL1 levels across diverse ancestries.
- To compare APOL1 measurements using three distinct proteomic technologies.
Main Methods:
- Analysis of APOL1 genetic variants and plasma protein levels in African and European ancestry cohorts.
- Utilized Olink, SomaLogic, and mass spectrometry for proteomic profiling.
- Performed quantitative trait loci (QTL) analysis to identify genetic associations.
Main Results:
- Disease-associated APOL1 variants (G1, G2) acted as cis-pQTLs for plasma APOL1 detected by Olink and SomaLogic, but not mass spectrometry.
- Proteomic platforms showed opposing effect directions for APOL1 variants.
- Kallikrein-kinin system variants demonstrated trans-pQTL effects on Olink, but not SomaLogic.
Conclusions:
- Proteomic platform differences in detecting APOL1 highlight sensitivity to protein conformation.
- Intrinsic APOL1 mutations and extrinsic kallikrein-kinin system activity may alter APOL1 structure.
- These conformational changes differentially impact APOL1 detection across proteomic assays.
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