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document
Genetic associations with lipoprotein subfractions provide information on their biological nature . Adverse levels of lipoproteins are highly heritable and constitute risk factors for cardiovascular outcomes . Hitherto , genome-wide association studies revealed 95 lipid-associated loci . However , due to the small effect sizes of these associations large sample numbers ( > 100 000 samples ) were needed . Here we show that analyzing more refined lipid phenotypes , namely lipoprotein subfractions , can increase the number of significantly associated loci compared with bulk high-density lipoprotein and low-density lipoprotein analysis in a study with identical sample numbers . Moreover , lipoprotein subfractions provide novel insight into the human lipid metabolism . We measured 15 lipoprotein subfractions ( L1-L15 ) in 1791 samples using ( 1 ) H-NMR ( nuclear magnetic resonance ) spectroscopy . Using cluster analyses , we quantified inter-relationships among lipoprotein subfractions . Additionally , we analyzed associations with subfractions at known lipid loci . We identified five distinct groups of subfractions : one ( L1 ) was only marginally captured by serum lipids and therefore extends our knowledge of lipoprotein biochemistry . During a lipid-tolerance test , L1 lost its special position . In the association analysis , we found that eight loci ( LIPC , CETP , PLTP , FADS1-2-3 , SORT1 , GCKR , APOB , APOA1 ) were associated with the subfractions , whereas only four loci ( CETP , SORT1 , GCKR , APOA1 ) were associated with serum lipids . For LIPC , we observed a 10-fold increase in the variance explained by our regression models . In conclusion , NMR-based fine mapping of lipoprotein subfractions provides novel information on their biological nature and strengthens the associations with genetic loci . Future clinical studies are now needed to investigate their biomedical relevance .
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Intervention_Physical
lipoprotein subfractions
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Intervention_Pharmacological
lipoproteins
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Intervention_Pharmacological
lipoprotein subfractions
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Intervention_Pharmacological
high-density lipoprotein
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Intervention_Pharmacological
low-density lipoprotein
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Intervention_Pharmacological
lipoprotein subfractions
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Intervention_Physical
15 lipoprotein subfractions ( L1-L15 )
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Intervention_Physical
lipoprotein subfractions
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Intervention_Physical
subfractions
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Intervention_Pharmacological
L1
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Intervention_Physical
L1
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Intervention_Physical
lipoprotein subfractions
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Participant_Condition
lipoprotein subfractions
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Participant_Condition
15 lipoprotein subfractions ( L1-L15 ) in 1791 samples using ( 1 ) H-NMR ( nuclear magnetic resonance ) spectroscopy .