Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Ruifang Li-Gao; David Hughes; Jan Bert van Klinken; Renée de Mutsert; Frits R Rosendaal; Dennis O Mook-Kanamori; Nicholas John  Timpson; Ko Willems van Dijk

doi:10.2337/db21-0397

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Ruifang Li-Gao^*, David Hughes, Jan Bert van Klinken, Renée de Mutsert, Frits R Rosendaal, Dennis O Mook-Kanamori, Nicholas John Timpson, Ko Willems van Dijk

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

19 Citations (Scopus)

134 Downloads (Pure)

Abstract

Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined 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 (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (β [SE] −0.23 [0.03], P = 2.15 × 10−19). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: β [SE] 0.17 [0.03], P = 5.76 × 10−10; XXLVLDL cholesterol ester: β [SE] 0.17 [0.03], P = 9.74 × 10−10), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 × 10−8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, Matsuda insulin sensitivity index, and HbA1c in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate–corrected q <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 the ANKRD55 locus underlying diabetes.

Original language	English
Pages (from-to)	2932–2946
Number of pages	15
Journal	Diabetes
Volume	70
Issue number	12
Early online date	5 Oct 2021
DOIs	https://doi.org/10.2337/db21-0397
Publication status	Published - 1 Dec 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2337/db21-0397

Full-text PDF (accepted author manuscript)
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via the American Diabetes Association athttps://doi.org/10.2337/db21-0397 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 3.91 MB
Supplementary information PDF
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via the American Diabetes Association at https://doi.org/10.2337/db21-0397 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 596 KB
Supplementary figures PDF
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via the American Diabetes Association at https://doi.org/10.2337/db21-0397 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 2.47 MB
Supplementary information XLS
This is the accepted author manuscript (AAM). The final published version (version of record) is available online via the American Diabetes Association at https://doi.org/10.2337/db21-0397 . Please refer to any applicable terms of use of the publisher.
Accepted author manuscript, 9.74 MB

Handle.net

Persistent link

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility

Cite this

@article{b0164952f00c45afa328b5e76da53843,

title = "Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism",

abstract = "Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined 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 (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (β [SE] −0.23 [0.03], P = 2.15 × 10−19). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: β [SE] 0.17 [0.03], P = 5.76 × 10−10; XXLVLDL cholesterol ester: β [SE] 0.17 [0.03], P = 9.74 × 10−10), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 × 10−8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, Matsuda insulin sensitivity index, and HbA1c in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate–corrected q <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 the ANKRD55 locus underlying diabetes.",

author = "Ruifang Li-Gao and David Hughes and \{van Klinken\}, \{Jan Bert\} and \{de Mutsert\}, Ren{\'e}e and Rosendaal, \{Frits R\} and Mook-Kanamori, \{Dennis O\} and Timpson, \{Nicholas John\} and \{Willems van Dijk\}, Ko",

year = "2021",

month = dec,

day = "1",

doi = "10.2337/db21-0397",

language = "English",

volume = "70",

pages = "2932–2946",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "12",

}

TY - JOUR

T1 - Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

AU - Li-Gao, Ruifang

AU - Hughes, David

AU - van Klinken, Jan Bert

AU - de Mutsert, Renée

AU - Rosendaal, Frits R

AU - Mook-Kanamori, Dennis O

AU - Timpson, Nicholas John

AU - Willems van Dijk, Ko

PY - 2021/12/1

Y1 - 2021/12/1

N2 - Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined 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 (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (β [SE] −0.23 [0.03], P = 2.15 × 10−19). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: β [SE] 0.17 [0.03], P = 5.76 × 10−10; XXLVLDL cholesterol ester: β [SE] 0.17 [0.03], P = 9.74 × 10−10), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 × 10−8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, Matsuda insulin sensitivity index, and HbA1c in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate–corrected q <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 the ANKRD55 locus underlying diabetes.

AB - Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined 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 (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (β [SE] −0.23 [0.03], P = 2.15 × 10−19). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: β [SE] 0.17 [0.03], P = 5.76 × 10−10; XXLVLDL cholesterol ester: β [SE] 0.17 [0.03], P = 9.74 × 10−10), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 × 10−8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, Matsuda insulin sensitivity index, and HbA1c in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate–corrected q <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 the ANKRD55 locus underlying diabetes.

U2 - 10.2337/db21-0397

DO - 10.2337/db21-0397

M3 - Article (Academic Journal)

C2 - 34610981

SN - 0012-1797

VL - 70

SP - 2932

EP - 2946

JO - Diabetes

JF - Diabetes

IS - 12

ER -

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Abstract

UN SDGs

Access to Document

Handle.net

Fingerprint

Equipment

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

Cite this