Evidence map›Paper›PMID 41860901›Full record

ArticlePLoS genetics2026

An evaluation of age-varying genetic effects underlying body-mass index and blood pressure in the UK Biobank.

Genevieve M Leyden, Panagiota Pagoni, Grace M Power, David Carslake, Tom G Richardson, Kate Tilling, Gibran Hemani, George Davey Smith, Eleanor Sanderson

Abstract read
In one paragraph

Article in PLoS genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

9 authors.

Genevieve M LeydenMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0002-6024-4950
Panagiota PagoniMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Grace M PowerMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0002-5702-7728
David CarslakeMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0003-2916-4546
Tom G RichardsonMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.ORCID https://orcid.org/0000-0002-7918-2040
Kate TillingMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Gibran HemaniMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
George Davey SmithMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Eleanor SandersonMRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Genome-wide association studies (GWAS) are conventionally conducted in cohorts spanning a wide age-range. These studies typically assume that genetic associations are constant across different ages. Some traits, however, may have age-varying genetic associations. This has implications for the interpretation of genetic effects derived in downstream applications, such as Mendelian randomization (MR) analyses. In this study we conducted a series of age-stratified GWAS on individuals aged 40-69 years in the UK Biobank, for body-mass index (BMI) and three blood pressure traits (systolic, diastolic and pulsatile pressure (PP)) in 2-year age strata (N up to 26,330). We used a meta-regression approach to systematically identify single nucleotide polymorphisms (SNPs) with evidence for age interaction effects among trait-associated GWAS signals and additional loci genome-wide. Within an MR framework, we examine the relationship between BMI and blood pressure traits on cardiovascular and cardiometabolic outcomes (type-2 diabetes (T2D), stroke, peripheral artery disease (PAD), heart failure, coronary heart disease and atrial fibrillation). Next, we describe the effect of the SNP*Age interaction on those relationships in a modified inverse-variance weighted (ivw) analysis. We identified differential enrichment of age-interaction effects, which was trait dependent. For example, 10.3% of BMI discovery SNPs had evidence for an age-interaction in our data compared to 44.7% for PP (at P < 0.05). Our downstream MR and modified ivw analyses highlight the influence of age on the genetically predicted relationship between PP and adverse cardiovascular outcomes. For example, our results indicated that an increased rate of change in genetically predicted PP across the age period is associated with higher susceptibility to PAD (interaction odds ratio = 2.71; P = 1.82x10-13; 95%-CI: 2.08-3.53). The data generated in this project provides a valuable resource for further exploration of mechanisms relevant to the genetic architecture of complex traits and all summary data has been made accessible to the research community.

Indexed as

Blood PressureBody Mass IndexAdultAgedAge FactorsBiological Specimen BanksCardiovascular DiseasesDiabetes Mellitus, Type 2FemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single Nucleotide

Identifiers

PMID41860901
PMCPMC13029756

What Socratic 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 Socratic graph.