Journal Article

DZNE-2026-00458

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Population-based genome-wide association study of plasma complex lipid species.

Landstra, E.-N. (First author)DZNE* ; Imtiaz, M. A. (First author)DZNE* ; Talevi, V.DZNE* ; Eichelmann, F. ; Schulze, M. B. ; Aziz, N. A.DZNE* ; Breteler, M. M. B. (Last author)DZNE*

2026
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-026-72542-1

Abstract: The human lipidome comprises numerous complex lipids, dysregulation of which can contribute to the pathogenesis of a wide range of diseases. Despite the high heritability of parts of the lipidome, the genetic architecture of many circulating lipid species and their structure remains mostly unknown. Thus, we perform genome-wide association studies on 970 lipid species and 267 fatty acid composite measures using samples from the population-based Rhineland Study (n = 6096). We validate our findings using corresponding data from two other independent cohorts, including FinnGen (n = 7266) and EPIC-Potsdam (n = 1188). Out of 217 lead genomic loci, we find 136 to be novel, such as FDFT1. Using mendelian randomization and individual-level gene expression data, we identify 43 possible causal associations between candidate genes and corresponding lipid species, including FDFT1 - diacylglycerol (16:0/18:0). Our findings provide new insights into the intricate genetic underpinnings of lipid metabolism, which may facilitate risk stratification and discovery of new therapeutic targets.

Keyword(s): Humans (MeSH) ; Genome-Wide Association Study (MeSH) ; Lipids: blood (MeSH) ; Lipids: genetics (MeSH) ; Lipid Metabolism: genetics (MeSH) ; Male (MeSH) ; Female (MeSH) ; Mendelian Randomization Analysis (MeSH) ; Polymorphism, Single Nucleotide (MeSH) ; Middle Aged (MeSH) ; Adult (MeSH) ; Fatty Acids: blood (MeSH) ; Aged (MeSH) ; Lipidomics (MeSH) ; Lipids ; Fatty Acids

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Contributing Institute(s):

1. Population Health Sciences (AG Breteler)
2. Population & Clinical Neuroepidemiology (AG Aziz)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2026

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