Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

Gunn Helen Moen; Michel Nivard; Laxmi Bhatta; Nicole M. Warrington; Cristen Willer; Bjørn Olav Åsvold; Ben Brumpton; David M. Evans

doi:10.1007/s10519-022-10116-9

Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

Gunn Helen Moen^*, Michel Nivard, Laxmi Bhatta, Nicole M. Warrington, Cristen Willer, Bjørn Olav Åsvold, Ben Brumpton, David M. Evans

^*Corresponding author for this work

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

Abstract

The Barker Hypothesis posits that adverse intrauterine environments result in fetal growth restriction and increased risk of cardiometabolic disease through developmental compensations. Here we introduce a new statistical model using the genomic SEM software that is capable of simultaneously partitioning the genetic covariation between birthweight and cardiometabolic traits into maternally mediated and offspring mediated contributions. We model the covariance between birthweight and later life outcomes, such as blood pressure, non-fasting glucose, blood lipids and body mass index in the Norwegian HUNT study, consisting of 15,261 mother-eldest offspring pairs with genetic and phenotypic data. Application of this model showed some evidence for maternally mediated effects of systolic blood pressure on offspring birthweight, and pleiotropy between birthweight and non-fasting glucose mediated through the offspring genome. This underscores the importance of genetic links between birthweight and cardiometabolic phenotypes and offer alternative explanations to environmentally based hypotheses for the phenotypic correlation between these variables.

Original language	English
Pages (from-to)	40-52
Number of pages	13
Journal	Behavior Genetics
Volume	53
Issue number	1
DOIs	https://doi.org/10.1007/s10519-022-10116-9
Publication status	Published - Feb 2023

Bibliographical note

Funding Information:
G.H.M. is the recipient of an Australian Research Council Discovery Early Career Award (Project number: DE220101226) funded by the Australian Government and supported by the Research Council of Norway (Project grant: 325640) and Nils Normans minnegave. This work was also part of a Post doctorial mobility research grant (287198) from the Research council of Norway. LB, BOÅ and BMB receive support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. N.M.W is supported by an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (2008723). D.M.E. is supported by an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1137714) and this work was supported by NHMRC project grants (GNT1183074, GNT1157714).

Funding Information:
The authors would like to thank the research participants of the HUNT study. The Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotype quality control and imputation has been conducted by the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU.

Funding Information:
The authors would like to thank the research participants of the HUNT study. The Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotype quality control and imputation has been conducted by the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Birthweight
Developmental Origin of Health and Disease
Genomic SEM
Maternal genetic effect
Offspring genetic effect

UN SDGs

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

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10.1007/s10519-022-10116-9

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Moen, G. H., Nivard, M., Bhatta, L., Warrington, N. M., Willer, C., Åsvold, B. O., Brumpton, B., & Evans, D. M. (2023). Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study. Behavior Genetics, 53(1), 40-52. https://doi.org/10.1007/s10519-022-10116-9

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title = "Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study",

abstract = "The Barker Hypothesis posits that adverse intrauterine environments result in fetal growth restriction and increased risk of cardiometabolic disease through developmental compensations. Here we introduce a new statistical model using the genomic SEM software that is capable of simultaneously partitioning the genetic covariation between birthweight and cardiometabolic traits into maternally mediated and offspring mediated contributions. We model the covariance between birthweight and later life outcomes, such as blood pressure, non-fasting glucose, blood lipids and body mass index in the Norwegian HUNT study, consisting of 15,261 mother-eldest offspring pairs with genetic and phenotypic data. Application of this model showed some evidence for maternally mediated effects of systolic blood pressure on offspring birthweight, and pleiotropy between birthweight and non-fasting glucose mediated through the offspring genome. This underscores the importance of genetic links between birthweight and cardiometabolic phenotypes and offer alternative explanations to environmentally based hypotheses for the phenotypic correlation between these variables.",

keywords = "Birthweight, Developmental Origin of Health and Disease, Genomic SEM, Maternal genetic effect, Offspring genetic effect",

author = "Moen, {Gunn Helen} and Michel Nivard and Laxmi Bhatta and Warrington, {Nicole M.} and Cristen Willer and {\AA}svold, {Bj{\o}rn Olav} and Ben Brumpton and Evans, {David M.}",

note = "Funding Information: G.H.M. is the recipient of an Australian Research Council Discovery Early Career Award (Project number: DE220101226) funded by the Australian Government and supported by the Research Council of Norway (Project grant: 325640) and Nils Normans minnegave. This work was also part of a Post doctorial mobility research grant (287198) from the Research council of Norway. LB, BO{\AA} and BMB receive support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. N.M.W is supported by an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (2008723). D.M.E. is supported by an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1137714) and this work was supported by NHMRC project grants (GNT1183074, GNT1157714). Funding Information: The authors would like to thank the research participants of the HUNT study. The Tr{\o}ndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Tr{\o}ndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotype quality control and imputation has been conducted by the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU. Funding Information: The authors would like to thank the research participants of the HUNT study. The Tr{\o}ndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Tr{\o}ndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotype quality control and imputation has been conducted by the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2023",

month = feb,

doi = "10.1007/s10519-022-10116-9",

language = "English",

volume = "53",

pages = "40--52",

journal = "Behavior Genetics",

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publisher = "Springer",

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Moen, GH, Nivard, M, Bhatta, L, Warrington, NM, Willer, C, Åsvold, BO, Brumpton, B & Evans, DM 2023, 'Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study', Behavior Genetics, vol. 53, no. 1, pp. 40-52. https://doi.org/10.1007/s10519-022-10116-9

Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study. / Moen, Gunn Helen; Nivard, Michel; Bhatta, Laxmi et al.
In: Behavior Genetics, Vol. 53, No. 1, 02.2023, p. 40-52.

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

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T1 - Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

AU - Moen, Gunn Helen

AU - Nivard, Michel

AU - Bhatta, Laxmi

AU - Warrington, Nicole M.

AU - Willer, Cristen

AU - Åsvold, Bjørn Olav

AU - Brumpton, Ben

AU - Evans, David M.

N1 - Funding Information: G.H.M. is the recipient of an Australian Research Council Discovery Early Career Award (Project number: DE220101226) funded by the Australian Government and supported by the Research Council of Norway (Project grant: 325640) and Nils Normans minnegave. This work was also part of a Post doctorial mobility research grant (287198) from the Research council of Norway. LB, BOÅ and BMB receive support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for education, research and innovation in Central Norway; and the Joint Research Committee between St. Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. N.M.W is supported by an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (2008723). D.M.E. is supported by an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellowship (1137714) and this work was supported by NHMRC project grants (GNT1183074, GNT1157714). Funding Information: The authors would like to thank the research participants of the HUNT study. The Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotype quality control and imputation has been conducted by the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU. Funding Information: The authors would like to thank the research participants of the HUNT study. The Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. The genotyping in HUNT was financed by the National Institutes of Health (NIH); University of Michigan; The Research Council of Norway; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St. Olavs hospital and the Faculty of Medicine and Health Sciences, NTNU. The genotype quality control and imputation has been conducted by the K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, NTNU. Publisher Copyright: © 2022, The Author(s).

PY - 2023/2

Y1 - 2023/2

N2 - The Barker Hypothesis posits that adverse intrauterine environments result in fetal growth restriction and increased risk of cardiometabolic disease through developmental compensations. Here we introduce a new statistical model using the genomic SEM software that is capable of simultaneously partitioning the genetic covariation between birthweight and cardiometabolic traits into maternally mediated and offspring mediated contributions. We model the covariance between birthweight and later life outcomes, such as blood pressure, non-fasting glucose, blood lipids and body mass index in the Norwegian HUNT study, consisting of 15,261 mother-eldest offspring pairs with genetic and phenotypic data. Application of this model showed some evidence for maternally mediated effects of systolic blood pressure on offspring birthweight, and pleiotropy between birthweight and non-fasting glucose mediated through the offspring genome. This underscores the importance of genetic links between birthweight and cardiometabolic phenotypes and offer alternative explanations to environmentally based hypotheses for the phenotypic correlation between these variables.

AB - The Barker Hypothesis posits that adverse intrauterine environments result in fetal growth restriction and increased risk of cardiometabolic disease through developmental compensations. Here we introduce a new statistical model using the genomic SEM software that is capable of simultaneously partitioning the genetic covariation between birthweight and cardiometabolic traits into maternally mediated and offspring mediated contributions. We model the covariance between birthweight and later life outcomes, such as blood pressure, non-fasting glucose, blood lipids and body mass index in the Norwegian HUNT study, consisting of 15,261 mother-eldest offspring pairs with genetic and phenotypic data. Application of this model showed some evidence for maternally mediated effects of systolic blood pressure on offspring birthweight, and pleiotropy between birthweight and non-fasting glucose mediated through the offspring genome. This underscores the importance of genetic links between birthweight and cardiometabolic phenotypes and offer alternative explanations to environmentally based hypotheses for the phenotypic correlation between these variables.

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KW - Developmental Origin of Health and Disease

KW - Genomic SEM

KW - Maternal genetic effect

KW - Offspring genetic effect

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Using Genomic Structural Equation Modeling to Partition the Genetic Covariance Between Birthweight and Cardiometabolic Risk Factors into Maternal and Offspring Components in the Norwegian HUNT Study

Abstract

Bibliographical note

Keywords

UN SDGs

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