Evidence mapPaperPMID 42426908Full record

ArticleGenome biology2026

Genome-wide association studies of missing metabolite measures from two population-based studies.

Tariq O Faquih, Mohammed Aslam Imtiaz, Valentina Talevi, Elvire N Landstra, Astrid van Hylckama Vlieg, Ruifang Li-Gao, Frits R Rosendaal, Raymond Noordam, Diana van Heemst, Dennis O Mook-Kanamori and 3 more

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Article in Genome biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Tariq O Faquih *Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Mohammed Aslam Imtiaz *German Centre for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany.
Valentina TaleviGerman Centre for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany.
Elvire N LandstraGerman Centre for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany.
Astrid van Hylckama VliegDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Ruifang Li-GaoDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Frits R RosendaalDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Raymond NoordamDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Diana van HeemstDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Monique M B Breteler *German Centre for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany.
N Ahmad Aziz *German Centre for Neurodegenerative Diseases (DZNE), Population Health Sciences, Bonn, Germany. Ahmad.Aziz@dzne.de.
Ko Willems van Dijk *Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. k.willems_van_dijk@lumc.nl.

Funding

Dutch Science Organization 916.14.023German Research Foundation EXC2151-390873048Research Council Starting Grant 101041677VELUX Stiftung 1156
6 · The paper itself

Abstract

backgroundMetabolomic analyses are increasingly applied in both etiological and predictive research, but frequently report missing values, which are then either imputed or removed from the analyses, and not examined as true missingness due to altered metabolism. We hypothesized that interindividual genetic variation may account for part of this missingness.

resultsWe perform a logistic GWAS of metabolite missingness from an untargeted mass spectrometry-based platform in the Netherlands Epidemiology of Obesity Study (N = 594) and the Rhineland Study (N = 4,165). We consider metabolites missing in 10%-90% of individuals in both cohorts (N = 224). GWAS meta-analyses of these metabolites' probability of missingness revealed 55 metabolome-wide significant associations, including 42 novel ones (p < 1.58 × 10

conclusionsDespite considerable pleiotropy, the majority of identified SNP- 'missing metabolite' associations are biologically plausible, relating to beta-oxidation, bile acids, steroids, and xenobiotics metabolism. These findings suggest that missing values in metabolomics are partially non-random and reflect potential genetic variation.

Indexed as

Genome-Wide Association StudyMetabolomeMetabolomicsHumansNetherlandsObesityPolymorphism, Single NucleotideGenome-wide association studyInborn errors of metabolismMetabolomicsMissing measurementsPoor metabolizers

Identifiers

PMID42426908
PMCPMC13352909

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