Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood
Zheng, Yan ; Estampador, Angela LU ; V. Varga, Tibor LU ; Orho-Melander, Marju LU ; Schulz, Christina-Alexandra LU ; Ericson, Ulrika LU ; Sonestedt, Emily LU
and Qi, Lu
(2020)
In European Journal of Epidemiology
35(7).
p.685-697
- 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... (More)
- 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. © 2020, Springer Nature B.V. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8ab72258-1588-4924-ab2c-8b30a0ec199b
- author
- Zheng, Yan
; Estampador, Angela
LU
; V. Varga, Tibor
LU
; Orho-Melander, Marju
LU
; Schulz, Christina-Alexandra
LU
; Ericson, Ulrika
LU
; Sonestedt, Emily
LU
and Qi, Lu
- author collaboration
- organization
- publishing date
- 2020-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Birthweight, Blood pressure, Causal association, Hypertension, Mendelian randomization
- in
- European Journal of Epidemiology
- volume
- 35
- issue
- 7
- pages
- 13 pages
- publisher
- Springer
- external identifiers
-
- scopus:85085090306
- pmid:32383070
- ISSN
- 1573-7284
- DOI
- 10.1007/s10654-020-00638-z
- language
- English
- LU publication?
- yes
- id
- 8ab72258-1588-4924-ab2c-8b30a0ec199b
- date added to LUP
- 2020-06-23 11:32:13
- date last changed
- 2022-04-18 23:04:44
@article{8ab72258-1588-4924-ab2c-8b30a0ec199b,
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. © 2020, Springer Nature B.V.}},
author = {{Zheng, Yan and Estampador, Angela and V. Varga, Tibor and Orho-Melander, Marju and Schulz, Christina-Alexandra and Ericson, Ulrika and Sonestedt, Emily and Qi, Lu}},
issn = {{1573-7284}},
keywords = {{Birthweight; Blood pressure; Causal association; Hypertension; Mendelian randomization}},
language = {{eng}},
number = {{7}},
pages = {{685--697}},
publisher = {{Springer}},
series = {{European Journal of Epidemiology}},
title = {{Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood}},
url = {{http://dx.doi.org/10.1007/s10654-020-00638-z}},
doi = {{10.1007/s10654-020-00638-z}},
volume = {{35}},
year = {{2020}},
}