A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Uncovering the complex genetic architecture of human plasma lipidome using machine learning methods




TekijätLehtimäki Miikael, Mishra Binisha H., Del-Val Coral, Lyytikäinen Leo-Pekka, Kähönen Mika, Cloninger C. Robert, Raitakari Olli T., Laaksonen Reijo, Zwir Igor, Lehtimäki Terho, Mishra Pashupati P.

KustantajaNature Research

Julkaisuvuosi2023

JournalScientific Reports

Tietokannassa oleva lehden nimiScientific Reports

Artikkelin numero3078

Vuosikerta13

Numero1

eISSN2045-2322

DOIhttps://doi.org/10.1038/s41598-023-30168-z

Verkko-osoitehttps://doi.org/10.1038/s41598-023-30168-z

Rinnakkaistallenteen osoitehttps://research.utu.fi/converis/portal/detail/Publication/179127177


Tiivistelmä

Genetic architecture of plasma lipidome provides insights into regulation of lipid metabolism and related diseases. We applied an unsupervised machine learning method, PGMRA, to discover phenotype-genotype many-to-many relations between genotype and plasma lipidome (phenotype) in order to identify the genetic architecture of plasma lipidome profiled from 1,426 Finnish individuals aged 30–45 years. PGMRA involves biclustering genotype and lipidome data independently followed by their inter-domain integration based on hypergeometric tests of the number of shared individuals. Pathway enrichment analysis was performed on the SNP sets to identify their associated biological processes. We identified 93 statistically significant (hypergeometric p-value < 0.01) lipidome-genotype relations. Genotype biclusters in these 93 relations contained 5977 SNPs across 3164 genes. Twenty nine of the 93 relations contained genotype biclusters with more than 50% unique SNPs and participants, thus representing most distinct subgroups. We identified 30 significantly enriched biological processes among the SNPs involved in 21 of these 29 most distinct genotype-lipidome subgroups through which the identified genetic variants can influence and regulate plasma lipid related metabolism and profiles. This study identified 29 distinct genotype-lipidome subgroups in the studied Finnish population that may have distinct disease trajectories and therefore could be useful in precision medicine research.


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Last updated on 2025-27-03 at 21:47