Abstract：
OBJECTIVE:Mendelian randomization is a popular technique for assessing and estimating the causal effects of risk factors. If genetic variants which are instrumental variables for a risk factor are shown to be additionally associated with a disease outcome, then the risk factor is a cause of the disease. However, in many cases, the instrumental variable assumptions are not plausible, or are in doubt. In this paper, we provide a theoretical classification of scenarios in which a causal conclusion is justified or not justified, and discuss the interpretation of causal effect estimates. RESULTS:A list of guidelines based on the 'Bradford Hill criteria' for judging the plausibility of a causal finding from an applied Mendelian randomization study is provided. We also give a framework for performing and interpreting investigations performed in the style of Mendelian randomization, but where the choice of genetic variants is statistically, rather than biologically motivated. Such analyses should not be assigned the same evidential weight as a Mendelian randomization investigation. CONCLUSION:We discuss the role of such investigations (in the style of Mendelian randomization), and what they add to our understanding of potential causal mechanisms. If the genetic variants are selected solely according to statistical criteria, and the biological roles of genetic variants are not investigated, this may be little more than what can be learned from a well-designed classical observational study.
journal_name
J Clin Epidemioljournal_title
Journal of clinical epidemiologyauthors
Burgess S,Butterworth AS,Thompson JRdoi
10.1016/j.jclinepi.2015.08.001subject
Has Abstractpub_date
2016-01-01 00:00:00pages
208-16eissn
0895-4356issn
1878-5921pii
S0895-4356(15)00376-5journal_volume
69pub_type
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章,meta分析,评审
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更新日期：2008-07-01 00:00:00
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journal_title：Journal of clinical epidemiology
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journal_title：Journal of clinical epidemiology
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/0895-4356(92)90144-c
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/j.jclinepi.2008.11.005
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pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：2003-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/s0895-4356(98)00094-8
更新日期：1998-11-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章,评审
doi：10.1016/j.jclinepi.2005.09.005
更新日期：2006-04-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/0895-4356(89)90076-0
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/0895-4356(92)90058-u
更新日期：1992-07-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/j.jclinepi.2014.06.013
更新日期：2014-12-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/j.jclinepi.2005.03.004
更新日期：2005-09-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/j.jclinepi.2004.10.021
更新日期：2005-07-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/s0895-4356(00)00241-9
更新日期：2000-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0895-4356(90)90013-f
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pub_type： 临床试验,杂志文章
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pub_type： 杂志文章
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journal_title：Journal of clinical epidemiology
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更新日期：2011-02-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/j.jclinepi.2007.02.002
更新日期：2007-11-01 00:00:00
abstract：:Pierre Charles Alexandre Louis (1787-1872) has been the direct or indirect mentor of influential U.S. and English scientists in public health, epidemiology, medicine, and biostatistics during the 19th and 20th century. Louis was primarily a clinician, but his name has been more closely associated with the history of e...
journal_title：Journal of clinical epidemiology
pub_type： 传,历史文章,杂志文章
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更新日期：1996-12-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/0895-4356(95)00551-x
更新日期：1996-04-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章
doi：10.1016/j.jclinepi.2015.05.029
更新日期：2015-09-01 00:00:00
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journal_title：Journal of clinical epidemiology
pub_type： 杂志文章,meta分析,评审
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更新日期：2013-03-01 00:00:00
