Evidence map›Paper›PMID 42006791›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Pitfalls in estimating and interpreting the contribution of ultra-rare genetic variants to the heritability of complex traits.

Huanwei Wang, Pierrick Wainschtein, Julia Sidorenko, Mulusew Fikere, Yuanxiang Zhang, Kathryn E Kemper, Zhili Zheng, Valentin Hivert, Jian Zeng, Michael E Goddard and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Huanwei WangInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Pierrick WainschteinInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Julia SidorenkoInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Mulusew FikereInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Yuanxiang ZhangInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Kathryn E KemperInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Zhili ZhengInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Valentin HivertInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Jian ZengInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Michael E GoddardPurdue University, West Lafayette, IN 47907, USA.
Peter M VisscherInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
Loic YengoInstitute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.

Funding

Estimating the genetic and environmental architecture of psychiatric disordersR01MH100141 · NIMH · UNIVERSITY OF COLORADO · PI KELLER, MATTHEW CHARLES · 2013 to 2022
$5.3M
NIMH NIH HHS R01 MH100141
6 · The paper itself

Abstract

Assessing the contribution of ultra-rare variants (minor allele frequency <0.01%) to the heritability of complex traits remains challenging due to limited understanding of potential biases. Here, we focus on singletons (that is, variants observed only once in the study sample), the most abundant class of ultra-rare variants, to showcase various confounders of heritability estimates and underline pitfalls in their interpretation. We show through theory, simulations, and analysis of 5,330,210 exome-sequenced singletons in 305,813 unrelated European-ancestry individuals in the UK Biobank that (i) population stratification induces both upward and downward biases in singleton-based heritability estimates (

Identifiers

PMID42006791
PMCPMC13086107

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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.