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Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism
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posted on 2021-10-05, 18:06 authored by Ruifang Li-Gao, David A. Hughes, Jan B. van Klinken, Renée de Mutsert, Frits R. Rosendaal, Dennis O. Mook-Kanamori, Nicholas J Timpson, Ko Willems van DijkHumans
spend the greater part of the day in a postprandial state. However, the genetic
basis of postprandial blood measures is relatively uncharted territory. We set
out to examine the genetics of variation in concentrations of postprandial metabolites
(t=150 min) in response to a liquid mixed meal through genome-wide association
studies (GWAS) performed in the Netherlands Epidemiology of Obesity study
(N=5,705). The metabolite response GWAS identified an association between
glucose change and rs10830963:G in the melatonin receptor 1B (beta (SE): -0.23
(0.03), P-value: 2.15×10-19). In addition, ANKRD55 locus led by rs458741:C showed strong associations to
extremely large VLDL particle (XXLVLDL) response (with XXLVLDLC: beta (SE):
0.17 (0.03) P-value: 5.76×10-10 and with XXLVLDLCE: beta (SE): 0.17
(0.03), P-value: 9.74×10-10), which also revealed strong
associations to body composition and diabetes in the UK Biobank (p-values<5×10-8).
Furthermore, the associations between XXLVLDL response and insulinogenic index,
HOMA-β, ISI matsuda index and HbA1c in the NEO study further implied the role
of chylomicron synthesis in diabetes (with FDR corrected q-value<0.05). To
conclude, genetic studies of
metabolomics change after a liquid meal illuminate novel pathways for glucose
and lipid metabolism. Further studies are warranted to corroborate biological
pathways of ANKRD55 locus underlying
diabetes.