Investigating a Potential Causal Relationship Between Maternal Blood Pressure During Pregnancy and Future Offspring Cardiometabolic Health

Geng Wang; Laxmi Bhatta; Gunn Helen Moen; Daniel Liang-Dar Hwang; John P Kemp; Tom Bond; Bjørn Olav Asvold; Ben M Brumpton; David Evans; Nicole Warrington

doi:10.1161/HYPERTENSIONAHA.121.17701

Investigating a Potential Causal Relationship Between Maternal Blood Pressure During Pregnancy and Future Offspring Cardiometabolic Health

Geng Wang, Laxmi Bhatta, Gunn Helen Moen, Daniel Liang-Dar Hwang, John P Kemp, Tom Bond, Bjørn Olav Asvold, Ben M Brumpton, David Evans, Nicole Warrington^*

^*Corresponding author for this work

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Abstract

Observational epidemiological studies have reported that higher maternal blood pressure during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic blood pressure (SBP) and diastolic blood pressure (DBP), and a range of cardiometabolic risk factors in the offspring of up to 29,708 genotyped mother-offspring pairs from the UK Biobank (UKB) and the Trøndelag Health (HUNT) studies. We conducted similar analyses in up to 21,423 father-offspring pairs from the same cohorts. We confirmed that the blood pressure associated genetic variants from the general population sample also had similar effects on maternal blood pressure during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal blood pressure is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life.

Original language	English
Pages (from-to)	170–177
Number of pages	8
Journal	Hypertension
Volume	79
Issue number	1
Early online date	17 Nov 2021
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.121.17701
Publication status	Published - 1 Jan 2022

Bibliographical note

Funding Information:
G. Wang is supported by The University of Queensland Graduate School Scholarship (UQGSS). D.M. Evans is funded by an Australian National Health and Medical Research Council Senior Research Fellowship (APP1137714), and this work was funded by NHMRC project grants (GNT1157714 and GNT1183074). N.M. Warrington is affiliated with a unit that is supported by the UK Medical Research Council (MC_UU_00011/3 and MC_UU_00011/6). J.P. Kemp is funded by a National Health and Medical Research Council (Australia) Investigator grant (GNT1177938). G.-H. Moen is supported by the Norwegian Research Council (Post doctorial mobility research grant 287198), the Norwegian Diabetes Association, Oslo Diabetes Research Centre, and Nils Normans minnegave. T.A. Bond works in/is affiliated with a unit that is supported by the UK Medical Research Council (MC_UU_00011/6) and is supported by the British Heart Foundation Accelerator Award at the University of Bristol (R100643-101). L. Bhatta, B.O. Åsvold, and B. Brumpton 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. The genotyping in HUNT was financed by the National Institute 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 UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC (Avon Longitudinal Study of Parents and Children). A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ); this research was specifically funded by Lifelong Health and Wellbeing (LLHW) via the MRC (G1001357), Wellcome Trust (WT092830/Z/10/Z and WT088806), and the British Heart Foundation (SP/07/008/24066). Genome-wide association studies (GWAS) data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This publication is the work of the authors and G. Wang, L. Bhatta, N.M. Warrington, D.M. Evans, and B. Brumpton will serve as guarantors for the contents of this article.

Publisher Copyright:
© 2021 The Authors.

Research Groups and Themes

ALSPAC

Keywords

adult children
blood pressure
cardiometabolic risk factors
cohort studies
genotype
pregnancy
Mendelian randomization analysis

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title = "Investigating a Potential Causal Relationship Between Maternal Blood Pressure During Pregnancy and Future Offspring Cardiometabolic Health",

abstract = "Observational epidemiological studies have reported that higher maternal blood pressure during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic blood pressure (SBP) and diastolic blood pressure (DBP), and a range of cardiometabolic risk factors in the offspring of up to 29,708 genotyped mother-offspring pairs from the UK Biobank (UKB) and the Tr{\o}ndelag Health (HUNT) studies. We conducted similar analyses in up to 21,423 father-offspring pairs from the same cohorts. We confirmed that the blood pressure associated genetic variants from the general population sample also had similar effects on maternal blood pressure during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal blood pressure is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life. ",

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note = "Funding Information: G. Wang is supported by The University of Queensland Graduate School Scholarship (UQGSS). D.M. Evans is funded by an Australian National Health and Medical Research Council Senior Research Fellowship (APP1137714), and this work was funded by NHMRC project grants (GNT1157714 and GNT1183074). N.M. Warrington is affiliated with a unit that is supported by the UK Medical Research Council (MC_UU_00011/3 and MC_UU_00011/6). J.P. Kemp is funded by a National Health and Medical Research Council (Australia) Investigator grant (GNT1177938). G.-H. Moen is supported by the Norwegian Research Council (Post doctorial mobility research grant 287198), the Norwegian Diabetes Association, Oslo Diabetes Research Centre, and Nils Normans minnegave. T.A. Bond works in/is affiliated with a unit that is supported by the UK Medical Research Council (MC_UU_00011/6) and is supported by the British Heart Foundation Accelerator Award at the University of Bristol (R100643-101). L. Bhatta, B.O. {\AA}svold, and B. Brumpton 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. The genotyping in HUNT was financed by the National Institute 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 UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC (Avon Longitudinal Study of Parents and Children). A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ); this research was specifically funded by Lifelong Health and Wellbeing (LLHW) via the MRC (G1001357), Wellcome Trust (WT092830/Z/10/Z and WT088806), and the British Heart Foundation (SP/07/008/24066). Genome-wide association studies (GWAS) data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. This publication is the work of the authors and G. Wang, L. Bhatta, N.M. Warrington, D.M. Evans, and B. Brumpton will serve as guarantors for the contents of this article. Publisher Copyright: {\textcopyright} 2021 The Authors.",

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N2 - Observational epidemiological studies have reported that higher maternal blood pressure during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic blood pressure (SBP) and diastolic blood pressure (DBP), and a range of cardiometabolic risk factors in the offspring of up to 29,708 genotyped mother-offspring pairs from the UK Biobank (UKB) and the Trøndelag Health (HUNT) studies. We conducted similar analyses in up to 21,423 father-offspring pairs from the same cohorts. We confirmed that the blood pressure associated genetic variants from the general population sample also had similar effects on maternal blood pressure during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal blood pressure is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life.

AB - Observational epidemiological studies have reported that higher maternal blood pressure during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic blood pressure (SBP) and diastolic blood pressure (DBP), and a range of cardiometabolic risk factors in the offspring of up to 29,708 genotyped mother-offspring pairs from the UK Biobank (UKB) and the Trøndelag Health (HUNT) studies. We conducted similar analyses in up to 21,423 father-offspring pairs from the same cohorts. We confirmed that the blood pressure associated genetic variants from the general population sample also had similar effects on maternal blood pressure during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal blood pressure is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life.

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KW - cardiometabolic risk factors

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KW - genotype

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JO - Hypertension

JF - Hypertension

IS - 1

ER -

Investigating a Potential Causal Relationship Between Maternal Blood Pressure During Pregnancy and Future Offspring Cardiometabolic Health

Abstract

Bibliographical note

Research Groups and Themes

Keywords

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