Significance filtering induces denominator selection bias in local genetic correlation: closed-form characterisation, a gate-aware correction, and an applicability diagnostic
Paquin, D.; Jain, R.
Show abstract
Local genetic correlation is estimated as a ratio of a local genetic covariance to the geometric mean of two local heritabilities. LAVA, the standard implementation, returns that ratio only where both traits clear a univariate heritability test at P < 0.05, a rule its documentation presents as a stabiliser. We show that it is a selection event acting on the denominator, and characterise what it does to the estimates that survive. Under the noncentral Wishart model LAVA's own interval routine assumes, the gate-conditional mean of the estimator is affine in the true correlation, with slope and intercept available in closed form from quantities every run already reports, that is, the components retained, the two univariate P-values, and the sample-overlap correlation. Attenuation is therefore a property of the analysis, not of the method. Across six psychiatric trait pairs the measured slope runs from 0.579 to 0.923 and the closed form predicts each to within 0.007 with nothing fitted to the panel, while within a single pair it runs from 0.371 to 0.971, so no single factor can correct it. Overlap and the filter jointly manufacture correlation where the truth is zero, most where power is lowest. We invert the closed form into a gate-aware correction, which reduces mean absolute bias from 0.247 to 0.026 over 48 simulation cells, and pair it with a diagnostic that decides whether the correction is identified. Three pairs fail it, all three sharing one trait whose local heritabilities are indistinguishable from a complete local null.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The Causal Pivot: A Structural Approach to Genetic Heterogeneity and Variant Discovery in Complex Diseases 94%
- Estimating disease heritability from complex pedigrees allowing for ascertainment and covariates 93%
- Welch-weighted Egger regression reduces false positives due to correlated pleiotropy in Mendelian randomization 93%
Similar papers in this journal
- Kinship estimation bias carries over to heritability estimation bias using variance components 92%
- Hierarchical clustering of gene-level association statistics reveals shared and differential genetic architecture among traits in the UK Biobank 92%
- Private Genomes and Public SNPs: Homomorphic encryption of genotypes and phenotypes for shared quantitative genetics 92%
Similar papers in this journal
- LDAK-KVIK performs fast and powerful mixed-model association analysis of quantitative and binary phenotypes 93%
- Reconciling S-LDSC and LDAK functional enrichment estimates 93%
- Leveraging a machine learning derived surrogate phenotype to improve power for genome-wide association studies of partially missing phenotypes in population biobanks 92%
Similar papers in this journal
- The PPLD has advantages over conventional regression methods in application to moderately sized genome-wide association studies 92%
- Partitioning gene-based variance of complex traits by gene score regression 92%
- Estimating the heritability of psychological measures in the Human Connectome Project dataset 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.