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Koller, A.* ; Schnitzer, F.* ; Kollerits, B.* ; Lamina, C.* ; Moix, S.* ; Claringbould, A.* ; Mishra, B.H.* ; Lu, H.* ; Schachtl-Riess, J.F.* ; Forer, L.* ; Gieger, C. ; Kheirkhah, A.* ; Lehtimäki, T.* ; Marques-Vidal, P.* ; Schönherr, S.* ; Stark, K.J.* ; Würzner, R.* ; Eckardt, K.* ; Heid, I.M.* ; Kavousi, M.* ; Köttgen, A.* ; Raitakari, O.* ; Sijbrands, E.J.G.* ; Peters, A. ; Vollenweider, P.* ; Kronenberg, F.*

Genetic architecture and cross-platform validation of apolipoprotein A-IV concentrations.

Genome Biol., DOI: 10.1186/s13059-026-04196-7 (2026)
Research data DOI PMC
Open Access Gold as soon as Publ. Version/Full Text is submitted to ZB.
BACKGROUND: Apolipoprotein A-IV (apoA-IV) plays key roles in lipid metabolism, reverse cholesterol transport, and kidney function, yet its genetic determinants remain poorly defined. We conduct a genome-wide association study (GWAS) meta-analysis of apoA-IV concentrations measured by ELISA in 25,181 individuals and combine these with proteomic data from 33,995 UK Biobank participants (Olink platform), yielding a total sample of 59,176. We perform genetic correlations and colocalization analyses to explore links with lipid, renal, and other complex traits. RESULTS: The GWAS identifies several novel loci to be associated with apoA-IV concentrations (TDRD5, DPP4, MYL3, MORC1, MCUB, GATA4, ZPR1, UMOD, GLP2R, SLC38A10 and APOE) besides two previously identified loci (APOA5-A4-C3-A1 cluster and KLKB1). Cross-platform comparison shows strong concordance of effect directions and magnitudes, underscoring the robustness of findings across measurement techniques. Global genetic correlation reveals significant shared genetic architecture between apoA-IV, kidney function and HDL-cholesterol, while colocalization supports shared causal variants with lipid, renal, and hematological phenotypes, suggesting biologically relevant pathways. CONCLUSION: These results provide a comprehensive overview of the genetic architecture of apoA-IV and suggest mechanistic links to lipid metabolism, kidney function and blood-related traits. Our findings refine the role of apoA-IV as a potential biomarker and inform future epidemiological research.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genetic Architecture ; Biobank ; Genome-wide Association Study ; Human Genetics ; Concordance ; Apolipoprotein E ; Apolipoprotein B ; Genetic Association
ISSN (print) / ISBN 1474-760X
e-ISSN 1465-6906
Journal Genome Biology
Publisher Springer
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants Austrian Science Fund
Tiroler Nachwuchsforscher∗innen Förderung