A multivariant recall-by-genotype study of the metabolomic signature of BMI

Si Fang; Kaitlin H Wade; David A Hughes; Sophie J FitzGibbon; Vikki L Yip; Nicholas John  Timpson; Laura J Corbin

doi:10.1002/oby.23441

A multivariant recall-by-genotype study of the metabolomic signature of BMI

Si Fang, Kaitlin H Wade, David A Hughes, Sophie J FitzGibbon, Vikki L Yip, Nicholas John Timpson, Laura J Corbin^*

^*Corresponding author for this work

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

7 Citations (Scopus)

200 Downloads (Pure)

Abstract

Objective
This study estimated the effect of BMI on circulating metabolites in young adults using a recall-by-genotype study design.

Methods
A recall-by-genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites.

Results
After correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high-BMI GRS group (β = −0.32, 95% CI: −0.46 to −0.18, Benjamini-Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet-related metabolites, including hippurate, which had lower mean abundance in individuals in the high-BMI GRS group (β = −0.29, 95% CI: −0.44 to −0.15, Benjamini-Hochberg adjusted p = 0.008).

Conclusions
Together with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.

Original language	English
Pages (from-to)	1298-1310
Number of pages	13
Journal	Obesity
Volume	30
Issue number	6
Early online date	22 May 2022
DOIs	https://doi.org/10.1002/oby.23441
Publication status	Published - 8 Jun 2022

Bibliographical note

Funding Information:
NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the primary investigator (PI) of the Avon Longitudinal Study of Parents and Children (ALSPAC; MRC & WT 217065/Z/19/Z), is supported by the University of Bristol National Institute for Health Research Biomedical Research Centre and the Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/1), and works within the Cancer Research UK (CRUK) Integrative Cancer Epidemiology Programme (C18281/A29019). At the start of this project, KHW was supported by a Wellcome Trust Investigator grant (PI: NJT; 202802/Z/16/Z) and then the Elizabeth Blackwell Institute for Health Research, University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (204813/Z/16/Z). DAH and LJC are supported by a Wellcome Trust Investigator grant (PI: NJT; 202802/Z/16/Z) and work within the Medical Research Council Integrative Epidemiology Unit (MC_UU_12013/3). S. Fang is supported by a Wellcome Trust PhD studentship (108902/Z/15/Z). The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( https://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). This research was funded in whole, or in part, by the Wellcome Trust (202802/Z/16/Z). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) public copyright license to any author accepted manuscript version arising from this submission.

Publisher Copyright:
© 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).

Research Groups and Themes

ALSPAC

Keywords

Body Mass Index
Genetic scores
Recall by Genotype
metabolomics

Access to Document

10.1002/oby.23441

Full-text PDF (final published version)
This is the final published version of the article (version of record). It first appeared online via Wiley at https://doi.org/10.1002/oby.23441. Please refer to any applicable terms of use of the publisher.
Final published version, 10.8 MBLicence: CC BY

Handle.net

Persistent link

Embargoed Document

Full-text PDF (author accepted manuscript)
Accepted author manuscript, 1.12 MB
Licence: Unspecified
Request copy

Embargoed Document

Supplementary information Excel
Accepted author manuscript, 414 KB
Licence: Unspecified
Request copy

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research

Cite this

@article{cc57c004d6974beb82086f0111989040,

title = "A multivariant recall-by-genotype study of the metabolomic signature of BMI",

abstract = "ObjectiveThis study estimated the effect of BMI on circulating metabolites in young adults using a recall-by-genotype study design.MethodsA recall-by-genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites.ResultsAfter correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high-BMI GRS group (β = −0.32, 95% CI: −0.46 to −0.18, Benjamini-Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet-related metabolites, including hippurate, which had lower mean abundance in individuals in the high-BMI GRS group (β = −0.29, 95% CI: −0.44 to −0.15, Benjamini-Hochberg adjusted p = 0.008).ConclusionsTogether with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.",

keywords = "Body Mass Index, Genetic scores, Recall by Genotype, metabolomics",

author = "Si Fang and Wade, {Kaitlin H} and Hughes, {David A} and FitzGibbon, {Sophie J} and Yip, {Vikki L} and Timpson, {Nicholas John} and Corbin, {Laura J}",

note = "Funding Information: NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the primary investigator (PI) of the Avon Longitudinal Study of Parents and Children (ALSPAC; MRC & WT 217065/Z/19/Z), is supported by the University of Bristol National Institute for Health Research Biomedical Research Centre and the Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/1), and works within the Cancer Research UK (CRUK) Integrative Cancer Epidemiology Programme (C18281/A29019). At the start of this project, KHW was supported by a Wellcome Trust Investigator grant (PI: NJT; 202802/Z/16/Z) and then the Elizabeth Blackwell Institute for Health Research, University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (204813/Z/16/Z). DAH and LJC are supported by a Wellcome Trust Investigator grant (PI: NJT; 202802/Z/16/Z) and work within the Medical Research Council Integrative Epidemiology Unit (MC_UU_12013/3). S. Fang is supported by a Wellcome Trust PhD studentship (108902/Z/15/Z). The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( https://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). This research was funded in whole, or in part, by the Wellcome Trust (202802/Z/16/Z). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) public copyright license to any author accepted manuscript version arising from this submission. Publisher Copyright: {\textcopyright} 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).",

year = "2022",

month = jun,

day = "8",

doi = "10.1002/oby.23441",

language = "English",

volume = "30",

pages = "1298--1310",

journal = "Obesity",

issn = "1930-7381",

publisher = "John Wiley & Sons, Inc",

number = "6",

}

TY - JOUR

T1 - A multivariant recall-by-genotype study of the metabolomic signature of BMI

AU - Fang, Si

AU - Wade, Kaitlin H

AU - Hughes, David A

AU - FitzGibbon, Sophie J

AU - Yip, Vikki L

AU - Timpson, Nicholas John

AU - Corbin, Laura J

N1 - Funding Information: NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the primary investigator (PI) of the Avon Longitudinal Study of Parents and Children (ALSPAC; MRC & WT 217065/Z/19/Z), is supported by the University of Bristol National Institute for Health Research Biomedical Research Centre and the Medical Research Council Integrative Epidemiology Unit (MC_UU_00011/1), and works within the Cancer Research UK (CRUK) Integrative Cancer Epidemiology Programme (C18281/A29019). At the start of this project, KHW was supported by a Wellcome Trust Investigator grant (PI: NJT; 202802/Z/16/Z) and then the Elizabeth Blackwell Institute for Health Research, University of Bristol and the Wellcome Trust Institutional Strategic Support Fund (204813/Z/16/Z). DAH and LJC are supported by a Wellcome Trust Investigator grant (PI: NJT; 202802/Z/16/Z) and work within the Medical Research Council Integrative Epidemiology Unit (MC_UU_12013/3). S. Fang is supported by a Wellcome Trust PhD studentship (108902/Z/15/Z). The UK Medical Research Council and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( https://www.bristol.ac.uk/alspac/external/documents/grant‐acknowledgements.pdf ). This research was funded in whole, or in part, by the Wellcome Trust (202802/Z/16/Z). For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) public copyright license to any author accepted manuscript version arising from this submission. Publisher Copyright: © 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society (TOS).

PY - 2022/6/8

Y1 - 2022/6/8

N2 - ObjectiveThis study estimated the effect of BMI on circulating metabolites in young adults using a recall-by-genotype study design.MethodsA recall-by-genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites.ResultsAfter correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high-BMI GRS group (β = −0.32, 95% CI: −0.46 to −0.18, Benjamini-Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet-related metabolites, including hippurate, which had lower mean abundance in individuals in the high-BMI GRS group (β = −0.29, 95% CI: −0.44 to −0.15, Benjamini-Hochberg adjusted p = 0.008).ConclusionsTogether with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.

AB - ObjectiveThis study estimated the effect of BMI on circulating metabolites in young adults using a recall-by-genotype study design.MethodsA recall-by-genotype study was implemented in the Avon Longitudinal Study of Parents and Children. Samples from 756 participants were selected for untargeted metabolomics analysis based on low versus high genetic liability for higher BMI defined by a genetic risk score (GRS). Regression analyses were performed to investigate associations between BMI GRS group and relative abundance of 973 metabolites.ResultsAfter correction for multiple testing, 29 metabolites were associated with BMI GRS group. Bilirubin was among the most strongly associated metabolites, with reduced levels measured in individuals in the high-BMI GRS group (β = −0.32, 95% CI: −0.46 to −0.18, Benjamini-Hochberg adjusted p = 0.005). This study observed associations between BMI GRS group and the levels of several potentially diet-related metabolites, including hippurate, which had lower mean abundance in individuals in the high-BMI GRS group (β = −0.29, 95% CI: −0.44 to −0.15, Benjamini-Hochberg adjusted p = 0.008).ConclusionsTogether with existing literature, these results suggest that a genetic predisposition to higher BMI captures differences in metabolism leading to adiposity gain. In the absence of prospective data, separating these effects from the downstream consequences of weight gain is challenging.

KW - Body Mass Index

KW - Genetic scores

KW - Recall by Genotype

KW - metabolomics

U2 - 10.1002/oby.23441

DO - 10.1002/oby.23441

M3 - Article (Academic Journal)

C2 - 35598895

SN - 1930-7381

VL - 30

SP - 1298

EP - 1310

JO - Obesity

JF - Obesity

IS - 6

ER -

A multivariant recall-by-genotype study of the metabolomic signature of BMI

Abstract

Bibliographical note

Research Groups and Themes

Keywords

Access to Document

Handle.net

Embargoed Document

Embargoed Document

Fingerprint

Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

Cite this