Abstract
Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = − 0.76, 95% CI − 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = − 0.06, 95% CI − 0.93 to 0.87 mmHg), or pulse pressure (β = − 0.65, 95% CI − 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.
| Original language | English |
|---|---|
| Pages (from-to) | 685-697 |
| Number of pages | 13 |
| Journal | European Journal of Epidemiology |
| Volume | 35 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2020 |
Bibliographical note
Publisher Copyright:© 2020, Springer Nature B.V.
Funding
This work was supported by Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01) and the National Key Research and Development Program of China (Grant No. 2016YFC1304801). YZ was supported by the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. For the funding information of each study within CHARGE-BIG consortium, please see Supplemental Table 8. Acknowledgements We thank the staff and the participants of the studies for their valuable contributions for their important contributions. We thank the following individuals for their assistance with data collection and analysis: Andre G. Uitterlinden (University of Leipzig, Leipzig, Germany), Chiea-Chuen Khor (Agency for Science Technology and Research, Singapore), Christian Hengstenberg (Technische Universit?t M?nchen, Germany), Fernando Rivadeneira (University Medical Center Rotterdam, the Netherlands), Jianjun Liu (Agency for Science Technology and Research, Singapore), JianMin Yuan (University of Pittsburgh Cancer Institute, Pittsburgh, USA), Lise Tarnow (University of Copenhagen, Hiller?d, Denmark), Markus Loeffler (University of Leipzig, Leipzig, Germany), Oluf Pedersen (University of Copenhagen, Denmark), Oscar Franco (Erasmus MC University Medical Center, Rotterdam, the Netherlands), Paul Franks (Lund University, Sk?ne University Hospital Malm?, Malm?, Sweden), ShuPei Tan (Singapore National Eye Centre, Singapore), Thomas Meitinger (Helmholtz Zentrum M?nchen?German Research Center for Environmental Health, Germany), Tine Marie Pedersen (University of Copenhagen, Denmark), Wanting Zhao (Singapore National Eye Centre, Singapore), Yik-Ying Teo (National University of Singapore, Singapore), Yoichiro Kamatani (RIKEN Center for Integrative Medical Sciences, Japan), Yuan Shi (Singapore National Eye Centre, Singapore), Ilja Demuth (Charit? - Universit?tsmedizin Berlin, Germany), Lars Bertram (Technische Universit?t M?nchen, Germany), Linda S. Adair (University of North Carolina, USA), Cyrus Cooper (University of Southampton, Southampton General Hospital, Southampton, UK), Hazel Inskip (University of Southampton, Southampton General Hospital, Southampton, UK), Sarah Crozier (University of Southampton, Southampton General Hospital, Southampton, UK), Elaine Dennison (MRC Lifecourse Epidemiology Unit, Southampton, UK), and Karen Jameson (MRC Lifecourse Epidemiology Unit, Southampton, UK)
| Funders | Funder number |
|---|---|
| Elaine Dennison | |
| Karen Jameson | |
| Lars Bertram | |
| Markus Loeffler | |
| Singapore National Eye Centre | |
| Southampton General Hospital | |
| Thomas Meitinger | |
| Yuan Shi | |
| National Heart, Lung, and Blood Institute (NHLBI) | R01HL034594 |
| National Heart, Lung, and Blood Institute (NHLBI) | |
| University of Pittsburgh Cancer Institute | |
| Medical Research Council | |
| University of Southampton Medical School and University Hospital Southampton NHS Foundation Trust | |
| Agency for Science Technology and Research | |
| National University Hospital, Singapore | |
| Københavns Universitet | |
| Science and Technology Commission of Shanghai Municipality | 2017SHZDZX01 |
| Science and Technology Commission of Shanghai Municipality | |
| Technische Universität München | |
| Universität Leipzig | |
| National Key Basic Research and Development Program of China | 2016YFC1304801 |
| National Key Basic Research and Development Program of China | |
| Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning |
Keywords
- Birthweight
- Blood pressure
- Causal association
- Hypertension
- Mendelian randomization
ASJC Scopus subject areas
- Epidemiology
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