Evidence map›Paper›PMID 41503465›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Individuals whose phenotype deviates from genetic expectation defined by common variation are enriched for rare damaging variants in genes that cause rare disease.

Nikolas A Baya, Frederik H Lassen, Barney Hill, Samvida S Venkatesh, Hannah Currant, Cecilia M Lindgren, Duncan S Palmer

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Nikolas A BayaBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-4681-374X
Frederik H LassenBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-0312-209X
Barney HillBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-7417-1393
Samvida S VenkateshBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0001-7680-1208
Hannah CurrantBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0003-2764-6787
Cecilia M LindgrenBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-4903-9374
Duncan S PalmerBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.ORCID 0000-0002-0824-0047

Funding

The Massachusetts General Hospital Harvard Center for Reproductive MedicineP50HD104224 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2021 to 2025
$7.8M
Gates Foundation INV-024200NICHD NIH HHS P50 HD104224Wellcome Trust
6 · The paper itself

Abstract

Polygenic scores (PGS) predict complex traits and stratify disease risk but often fail to fully capture individual-level variation. "Misaligned" individuals, whose observed phenotypes deviate from their genetically expected values based on polygenic scores (PGS), provide a powerful model for identifying factors beyond common-variant effects, including additional genetic factors. Here, we apply misalignment classification and enrichment testing frameworks to seven continuous and three dichotomous traits, assessing whether misaligned individuals in the UK Biobank are enriched for rare (minor allele frequency (MAF) < 0.1%) damaging genetic variation. We identify significant enrichment (false discovery rate (FDR)-adjusted

Identifiers

PMID41503465
PMCPMC12772651

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.