Evidence mapPaperPMID 39579208Full record

ArticleDiabetologia2025

A polygenic risk score derived from common variants of monogenic diabetes genes is associated with young-onset type 2 diabetes and cardiovascular-kidney complications.

Chun-Kwan O, Baoqi Fan, Sandra T F Tsoi, Claudia H T Tam, Raymond Wan, Eric S H Lau, Mai Shi, Cadmon K P Lim, Gechang Yu, Jane P Y Ho and 7 more

Abstract read
In one paragraph

Article in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
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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

17 authors.

Chun-Kwan ODepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0009-0009-3904-8056
Baoqi FanDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0001-6728-419X
Sandra T F TsoiDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
Claudia H T TamDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-9169-0013
Raymond WanDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0003-3202-7008
Eric S H LauDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0003-1581-5643
Mai ShiDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-2798-3268
Cadmon K P LimDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0001-5523-9199
Gechang YuDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-6887-6733
Jane P Y HoDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0009-0004-0071-959X
Elaine Y K ChowDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-4147-3387
Alice P S KongDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0001-8927-6764
Risa OzakiDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-2564-0560
Wing Yee SoDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0001-8078-7402
Ronald C W MaDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-1227-803X
Andrea O Y LukDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.ORCID http://orcid.org/0000-0002-5244-6069
Juliana C N ChanDepartment of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. jchan@cuhk.edu.hk.ORCID http://orcid.org/0000-0003-1325-1194

Funding

Hong Kong Government Health and Medical Research Fund Commissioned Research CFS-CUHK2
6 · The paper itself

Abstract

aims/hypothesisMonogenic diabetes is caused by rare mutations in genes usually implicated in beta cell biology. Common variants of monogenic diabetes genes (MDG) may jointly influence the risk of young-onset type 2 diabetes (YOD, diagnosed before the age of 40 years) and cardiovascular and kidney events.

methodsUsing whole-exome sequencing data, we constructed a weighted polygenic risk score (wPRS) consisting of 135 common variants (minor allele frequency >0.01) of 34 MDG based on r

resultsIn the discovery cohort, the OR of the 135 common variants for YOD ranged from 1.00 to 2.61. In the validation cohort (920 YOD and 4910 non-YOD), top-10%-wPRS was associated with an OR of 1.42 (95% CI 1.03, 1.95, p=0.033) for YOD compared with bottom-10%-wPRS. In 2313 individuals with type 2 diabetes (median [IQR]: age 53.4 [45.4-61.7] years; disease duration 4.0 [1.0-9.0] years) observed for a median (IQR) of 17.5 (14.4-21.8) years, standardised wPRS was associated with increased HR for incident cardiovascular events (1.16 [95% CI 1.06, 1.27], p=0.001), kidney events (1.09 [95% CI 1.02, 1.16], p=0.013) and cardiovascular-kidney events (1.10 [95% CI 1.03, 1.16], p=0.003). Using the 'bottom-20%-wPRS plus baseline disease duration <5 years' group as referent, the 'top-20%-wPRS plus baseline disease duration 5 to <10 years' group had unadjusted and adjusted HR of 1.60 (95% CI 1.17, 2.19, p=0.003) and 1.62 (95% CI 1.16, 2.26, p=0.005), respectively, for cardiovascular-kidney events compared with 1.38 (95% CI 0.97, 1.98, p=0.075) and 1.06 (95% CI 0.72, 1.57, p=0.752) in the 'bottom-20%-wPRS plus baseline disease duration ≥10 years' group. CONCLUSIONS/

interpretationCommon variants of MDG increased risk for YOD and cardiovascular-kidney events.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic NephropathiesMultifactorial InheritanceAdultAge of OnsetCase-Control StudiesCross-Sectional StudiesFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansMaleMiddle AgedRisk FactorsComplicationsGeneticsMODYPolygenic risk scoresWhole-exome sequencingYoung-onset diabetes

Identifiers

PMID39579208
PMCPMC11732898

What Socratic holds

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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.