Evidence map›Paper›PMID 37461573›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Exome-wide evidence of compound heterozygous effects across common phenotypes in the UK Biobank.

Frederik H Lassen, Samvida S Venkatesh, Nikolas Baya, Wei Zhou, Alex Bloemendal, Benjamin M Neale, Benedikt M Kessler, Nicola Whiffin, Cecilia M Lindgren, Duncan S Palmer

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. 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, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Frederik H LassenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Samvida S VenkateshWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Nikolas BayaWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Wei ZhouProgram in Medical and Population Genetics Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alex BloemendalProgram in Medical and Population Genetics Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Benjamin M NealeProgram in Medical and Population Genetics Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Benedikt M KesslerTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Nicola WhiffinWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Cecilia M LindgrenWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
Duncan S PalmerBig Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, United Kingdom.
Broad Institute · USCentre for Human Genetics · GBUniversity of Oxford · GB

Funding

The Massachusetts General Hospital Harvard Center for Reproductive MedicineP50HD104224 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI TALKOWSKI, MICHAEL E · 2021 to 2025
$7.8M
An integrative approach to disease gene discovery combining genetic variation, gene expression, and epigenetics.K99HG012222 · NHGRI · MASSACHUSETTS GENERAL HOSPITAL · PI ZHOU, WEI · 2022 to 2023
$319k
NHGRI NIH HHS K99 HG012222NICHD NIH HHS P50 HD104224Wellcome Trust
6 · The paper itself

Abstract

Exome-sequencing association studies have successfully linked rare protein-coding variation to risk of thousands of diseases. However, the relationship between rare deleterious compound heterozygous (CH) variation and their phenotypic impact has not been fully investigated. Here, we leverage advances in statistical phasing to accurately phase rare variants (MAF ~ 0.001%) in exome sequencing data from 175,587 UK Biobank (UKBB) participants, which we then systematically annotate to identify putatively deleterious CH coding variation. We show that 6.5% of individuals carry such damaging variants in the CH state, with 90% of variants occurring at MAF < 0.34%. Using a logistic mixed model framework, systematically accounting for relatedness, polygenic risk, nearby common variants, and rare variant burden, we investigate recessive effects in common complex diseases. We find six exome-wide significant (

Identifiers

PMID37461573
PMCPMC10350147
OpenAlexW4382930231

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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 Socratic graph.