Partial Identification of the Average Causal Effect in Multiple Study Populations: The Challenge of Combining Mendelian Randomization Studies

Diemer, EW (通讯作者),Harvard TH Chan Sch Publ Hlth, CAUSALab, 677 Huntington Ave, Boston, MA 02115 USA.
2023-1
Background:Researchers often use random-effects or fixed-effects meta-analysis to combine findings from multiple study populations. However, the causal interpretation of these models is not always clear, and they do not easily translate to settings where bounds, rather than point estimates, are computed. Methods:If bounds on an average causal effect of interest in a well-defined population are computed in multiple study populations under specified identifiability assumptions, then under those assumptions the average causal effect would lie within all study-specific bounds and thus the intersection of the study-specific bounds. We demonstrate this by pooling bounds on the average causal effect of prenatal alcohol exposure on attention deficit-hyperactivity disorder symptoms, computed in two European cohorts and under multiple sets of assumptions in Mendelian randomization (MR) analyses. Results:For all assumption sets considered, pooled bounds were wide and did not identify the direction of effect. The narrowest pooled bound computed implied the risk difference was between -4 and 34 percentage points. Conclusions:All pooled bounds computed in our application covered the null, illustrating how strongly point estimates from prior MR studies of this effect rely on within-study homogeneity assumptions. We discuss how the interpretation of both pooled bounds and point estimation in MR is complicated by possible heterogeneity of effects across populations.
EPIDEMIOLOGY
卷号:34|期号:1|页码:20-28
ISSN:1044-3983|收录类别:SCIE
语种
英语
来源机构
Erasmus University Rotterdam; Erasmus MC; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; University of Bristol; University of Bristol; Erasmus University Rotterdam; Erasmus MC; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Harvard University; Harvard T.H. Chan School of Public Health
资助信息
This project is supported by an innovation program under the Marie Sklodowska-Curie grant agreement no. 721567. S.A.S. is further sup-ported by a NWO/ZonMW Veni Grant (91617066). L.Z. was supported by a UK Medical Research Council fellowship (grant number G0902144). L.Z. was also supported by the UK MRC Integrative Epidemiology Unit (grant number: MC_UU_00011/1) and the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol. S.A.S. and E.W.D. are further supported by a US Department of Veterans Affairs Cooperative Studies Program study #2032. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and E.W.D., L.Z., and S.A.S. will serve as guarantors for the contents of this paper. A comprehen-sive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf).
被引频次(WOS)
0
被引频次(其他)
0
180天使用计数
2
2013以来使用计数
2
EISSN
1531-5487
出版年
2023-1
DOI
10.1097/EDE.0000000000001526
WOS学科分类
Public, Environmental & Occupational Health
学科领域
循证公共卫生
关键词
Instrumental variable Mendelian randomization Partial identification Research synthesis
资助机构
Marie Sklodowska-Curie NWO/ZonMW Veni UK Medical Research Council(UK Research & Innovation (UKRI)Medical Research Council UK (MRC)) UK MRC Integrative Epidemiology Unit National Institute for Health Research (NIHR) Bristol Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust University of Bristol US Department of Veterans Affairs(US Department of Veterans Affairs) Wellcome