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Mendelian Randomisation and Causal Inference in Observational Epidemiology

  • Nuala A Sheehan mail,

    To whom correspondence should be addressed.

  • Vanessa Didelez,
  • Paul R Burton,
  • Martin D Tobin
  • Published: August 26, 2008
  • DOI: 10.1371/journal.pmed.0050177

Reader Comments (3)

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Response to response on query

Posted by plosmedicine on 31 Mar 2009 at 00:30 GMT

Author: Eyal Shahar
Submitted Date: October 13, 2008
Published Date: October 15, 2008
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

The authors are right. I meant to criticize Gene 1 as an instrumental variable (IV) because I thought that one of the IV assumptions was violated (due to the path I mentioned--which is a backdoor path from Gene 1 to disease.) I missed your statement: "However, if Gene2 only affects the disease via its effect on the same intermediate exposure, as shown in Figure 3, there is no such violation." I did not know that. On another note: if the exposure has an effect on the disease, the IV must be either a cause of the disease (via the exposure) or a surrogate for a cause of the disease. In the case of a surrogate for a cause, the surrogate status is claimed by a causal arrow from the true cause to the IV.

No competing interests declared.