What question did this study set out to answer?

The aim is to investigate how neighboring genes share regulatory effects, challenging traditional single-gene assumptions.

March 26, 2026Open Access

Focus on single-gene effects limits discovery and interpretation of complex-trait-associated variants

Key Points

The aim is to investigate how neighboring genes share regulatory effects, challenging traditional single-gene assumptions.
Mapped QTLs on expression principal components of co-expressed neighboring genes.
Analyzed regulatory effects beyond single-gene frameworks.
Identified previously overlooked QTLs and GWAS colocalizations.
Discovered new QTLs that were not detected by standard single-gene methods.
Founded evidence of allelic proxitropy among neighboring genes.
Highlighted missed GWAS colocalizations that could enhance variant interpretation.

Abstract

Standard eQTL mapping and GWAS interpretation assume that each variant acts on one gene.However, neighboring genes can exhibit "allelic proxitropy," where regulatory effects are shared.To identify these effects, we map QTLs on expression principal components of co-expressed neighboring genes.We discover QTLs and GWAS colocalizations missed by single-gene methods.

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Cite This Study

Lawrence et al. (Sun,) studied this question.

synapsesocial.com/papers/69c4cc37fdc3bde448917785 https://doi.org/https://doi.org/10.1016/j.ajhg.2026.02.022

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