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Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.

TitleMendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood.
Publication TypeJournal Article
Year of Publication2020
AuthorsZheng, Y, Huang, T, Wang, T, Mei, Z, Sun, Z, Zhang, T, Ellervik, C, Chai, J-F, Sim, X, van Dam, RM, Tai, E-S, Koh, W-P, Dorajoo, R, Saw, S-M, Sabanayagam, C, Wong, TYin, Gupta, P, Rossing, P, Ahluwalia, TS, Vinding, RK, Bisgaard, H, Bønnelykke, K, Wang, Y, Graff, M, Voortman, T, van Rooij, FJA, Hofman, A, van Heemst, D, Noordam, R, Estampador, AC, Varga, TV, Enzenbach, C, Scholz, M, Thiery, J, Burkhardt, R, Orho-Melander, M, Schulz, C-A, Ericson, U, Sonestedt, E, Kubo, M, Akiyama, M, Zhou, A, Kilpeläinen, TO, Hansen, T, Kleber, ME, Delgado, G, McCarthy, M, Lemaitre, RN, Felix, JF, Jaddoe, VWV, Wu, Y, Mohlke, KL, Lehtimäki, T, Wang, CA, Pennell, CE, Schunkert, H, Kessler, T, Zeng, L, Willenborg, C, Peters, A, Lieb, W, Grote, V, Rzehak, P, Koletzko, B, Erdmann, J, Munz, M, Wu, T, He, M, Yu, C, Lecoeur, C, Froguel, P, Corella, D, Moreno, LA, Lai, C-Q, Pitkänen, N, Boreham, CA, Ridker, PM, Rosendaal, FR, de Mutsert, R, Power, C, Paternoster, L, Sørensen, TIA, Tjønneland, A, Overvad, K, Djoussé, L, Rivadeneira, F, Lee, NR, Raitakari, OT, Kähönen, M, Viikari, J, Langhendries, J-P, Escribano, J, Verduci, E, Dedoussis, G, König, I, Balkau, B, Coltell, O, Dallongeville, J, Meirhaeghe, A, Amouyel, P, Gottrand, F, Pahkala, K, Niinikoski, H, Hyppönen, E, März, W, Mackey, DA, Gruszfeld, D, Tucker, KL, Fumeron, F, Estruch, R, Ordovas, JM, Arnett, DK, Mook-Kanamori, DO, Mozaffarian, D, Psaty, BM, North, KE, Chasman, DI, Qi, L
JournalEur J Epidemiol
Volume35
Issue7
Pagination685-697
Date Published2020 Jul
ISSN1573-7284
Abstract<p>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.</p>
DOI10.1007/s10654-020-00638-z
Alternate JournalEur. J. Epidemiol.
PubMed ID32383070
Grant ListHL126024 / NH / NIH HHS / United States
HL034594 / NH / NIH HHS / United States
DK100383 / NH / NIH HHS / United States
DK091718 / NH / NIH HHS / United States
HL071981 / NH / NIH HHS / United States
HL073168 / NH / NIH HHS / United States
CA87969 / NH / NIH HHS / United States
CA49449 / NH / NIH HHS / United States
CA055075 / NH / NIH HHS / United States
HL34594 / NH / NIH HHS / United States
HL088521 / NH / NIH HHS / United States
U01HG004399 / NH / NIH HHS / United States
DK080140 / NH / NIH HHS / United States
P30DK46200 / NH / NIH HHS / United States
U01CA137088 / NH / NIH HHS / United States
U54CA155626 / NH / NIH HHS / United States
DK58845 / NH / NIH HHS / United States
DK098311 / NH / NIH HHS / United States
U01HG004728 / NH / NIH HHS / United States
EY015473 / NH / NIH HHS / United States
CA134958 / NH / NIH HHS / United States
DK70756 / NH / NIH HHS / United States
DK46200 / NH / NIH HHS / United States
2017SHZDZX01 / / Shanghai Municipal Science and Technology Major Project /
2016YFC1304801 / / National Key Research and Development Program of China /
HL126024 / NH / NIH HHS / United States
HL034594 / NH / NIH HHS / United States
DK100383 / NH / NIH HHS / United States
DK091718 / NH / NIH HHS / United States
HL071981 / NH / NIH HHS / United States
HL073168 / NH / NIH HHS / United States
CA87969 / NH / NIH HHS / United States
CA49449 / NH / NIH HHS / United States
CA055075 / NH / NIH HHS / United States
HL34594 / NH / NIH HHS / United States
HL088521 / NH / NIH HHS / United States
U01HG004399 / NH / NIH HHS / United States
DK080140 / NH / NIH HHS / United States
P30DK46200 / NH / NIH HHS / United States
U01CA137088 / NH / NIH HHS / United States
U54CA155626 / NH / NIH HHS / United States
DK58845 / NH / NIH HHS / United States
DK098311 / NH / NIH HHS / United States
U01HG004728 / NH / NIH HHS / United States
EY015473 / NH / NIH HHS / United States
CA134958 / NH / NIH HHS / United States
DK70756 / NH / NIH HHS / United States
DK46200 / NH / NIH HHS / United States
ePub date: 
20/05