ArticleGenetic epidemiology2026
Mendelianization: Concentrating Polygenic Signal Into a Single Causal Locus.
Article in Genetic epidemiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Complex disorders such as depression and alcohol use involve numerous genetic variants, and implicated loci continue to grow with sample size. This proliferation hampers interpretability, as the mechanisms by which so many variants jointly contribute to pathophysiology remain unclear. In contrast, classical Mendelian diseases arise from a single causal locus and are easier to interpret. We thus introduce Mendelianization-an algorithm distinct from Mendelian randomization-that learns weighted combinations of outcomes so that each aggregated phenotype concentrates association at one locus. We prove that this locus is causal under four structural assumptions natural to genetic data. The method handles partial sample overlap, provides calibrated hypothesis tests, maps coefficients to interpretable scales, and quantifies the degree of Mendelianism using summary
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