Evidence map›Paper›PMID 37420130›Full record

ArticleDiabetologia2023

Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children's cohort.

Kirsten Mehlig, Ronja Foraita, Rajini Nagrani, Marvin N Wright, Stefaan De Henauw, Dénes Molnár, Luis A Moreno, Paola Russo, Michael Tornaritis, Toomas Veidebaum and 4 more

Open access · hybridAbstract read
In one paragraph

Article in Diabetologia, 2023. 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
0.4field-weighted citation impact, top 34% of its field
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, 2 citations in OpenAlex.

  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

14 authors at 10 institutions in 9 countries.

Kirsten MehligSchool of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. kirsten.mehlig@gu.se.ORCID http://orcid.org/0000-0002-2653-0734
Ronja ForaitaLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID http://orcid.org/0000-0003-2216-6653
Rajini NagraniLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID http://orcid.org/0000-0002-1708-2319
Marvin N WrightLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID http://orcid.org/0000-0002-8542-6291
Stefaan De HenauwDepartment of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.ORCID http://orcid.org/0000-0003-4141-5432
Dénes MolnárDepartment of Paediatrics, Medical School, University of Pécs, Pécs, Hungary.ORCID http://orcid.org/0000-0002-3675-7019
Luis A MorenoGENUD (Growth, Exercise, Nutrition and Development) Research Group, University of Zaragoza, Zaragoza, Spain.ORCID http://orcid.org/0000-0003-0454-653X
Paola RussoInstitute of Food Sciences, National Research Council, Avellino, Italy.ORCID http://orcid.org/0000-0002-3603-0143
Michael TornaritisResearch and Education Institute of Child Health, Strovolos, Cyprus.
Toomas VeidebaumNational Institute for Health Development, Tallinn, Estonia.ORCID http://orcid.org/0000-0001-7659-8924
Lauren LissnerSchool of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-8296-2849
Jaakko KaprioInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-3716-2455
Iris PigeotLeibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany.ORCID http://orcid.org/0000-0001-7483-0726
I.Family consortium
Leibniz Institute for Prevention Research and Epidemiology - BIPS · DEUniversity of Gothenburg · SEGhent University · BEInstitute of Food Science · ITNational Institute for Health Development · EEUniversidad de Zaragoza · ESUniversity of Bremen · DEUniversity of Copenhagen · DKUniversity of Helsinki · FIUniversity of Pecs · HU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisThere is increasing evidence for the existence of shared genetic predictors of metabolic traits and neurodegenerative disease. We previously observed a U-shaped association between fasting insulin in middle-aged women and dementia up to 34 years later. In the present study, we performed genome-wide association (GWA) analyses for fasting serum insulin in European children with a focus on variants associated with the tails of the insulin distribution.

methodsGenotyping was successful in 2825 children aged 2-14 years at the time of insulin measurement. Because insulin levels vary during childhood, GWA analyses were based on age- and sex-specific z scores. Five percentile ranks of z-insulin were selected and modelled using logistic regression, i.e. the 15th, 25th, 50th, 75th and 85th percentile ranks (P15-P85). Additive genetic models were adjusted for age, sex, BMI, survey year, survey country and principal components derived from genetic data to account for ethnic heterogeneity. Quantile regression was used to determine whether associations with variants identified by GWA analyses differed across quantiles of log-insulin.

resultsA variant in the SLC28A1 gene (rs2122859) was associated with the 85th percentile rank of the insulin z score (P85, p value=3×10 CONCLUSIONS/

interpretationThe above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker-disease associations.

Indexed as

DementiaNeurodegenerative DiseasesFastingFemaleGenome-Wide Association StudyHumansInsulinMalePolymorphism, Single NucleotideUbiquitin-Protein LigasesInsulinSH3RF3 protein, humanUbiquitin-Protein LigasesBiomarkersBMIDementiaGeneticsGenome-wide association analysisInsulinMetabolic traitsObesityQuantile regressionSNPType 2 diabetes

Identifiers

PMID37420130
PMCPMC10473990
OpenAlexW4383500547

What Socratic holds

Textmetadata
LicenceCC BY
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.