14 research outputs found
Selection of invalid instruments can improve estimation in Mendelian randomization
Mendelian randomization (MR) is a widely-used method to identify causal links
between a risk factor and disease. A fundamental part of any MR analysis is to
choose appropriate genetic variants as instrumental variables. Current practice
usually involves selecting only those genetic variants that are deemed to
satisfy certain exclusion restrictions, in a bid to remove bias from unobserved
confounding. Many more genetic variants may violate these exclusion
restrictions due to unknown pleiotropic effects (i.e. direct effects on the
outcome not via the exposure), but their inclusion could increase the precision
of causal effect estimates at the cost of allowing some bias. We explore how to
optimally tackle this bias-variance trade-off by carefully choosing from many
weak and locally invalid instruments. Specifically, we study a focused
instrument selection approach for publicly available two-sample summary data on
genetic associations, whereby genetic variants are selected on the basis of how
they impact the asymptotic mean square error of causal effect estimates. We
show how different restrictions on the nature of pleiotropic effects have
important implications for the quality of post-selection inferences. In
particular, a focused selection approach under systematic pleiotropy allows for
consistent model selection, but in practice can be susceptible to winner's
curse biases. Whereas a more general form of idiosyncratic pleiotropy allows
only conservative model selection, but offers uniformly valid confidence
intervals. We propose a novel method to tighten honest confidence intervals
through support restrictions on pleiotropy. We apply our results to several
real data examples which suggest that the optimal selection of instruments does
not only involve biologically-justified valid instruments, but additionally
hundreds of potentially pleiotropic variants.Comment: 56 pages, 8 figure
Synthesizing efficacious genistein in conjugation with superparamagnetic Fe<sub>3</sub>O<sub>4</sub> decorated with bio-compatible carboxymethylated chitosan against acute leukemia lymphoma
Models of random wildlife movement with an application to distance sampling
In this paper we present three models of random wildlife movement: a one dimensional model of wildlife-observer encounters on roads, an analogous two dimensional model, and an further two-dimensional model that borrows from the ideas of statistical mechanics. We then derive unbiased estimates of wildlife density in terms of encounters for each of these models. By extending these results to incorporate uncertain detection, we suggest three novel distance sampling methods and briefly consider possible field applications
A Framework for Eliciting, Incorporating, and Disciplining Identification Beliefs in Linear Models
Yes, Wall Street, There Is a January Effect! Evidence from Laboratory Auctions
In the first experimental test of the January effect, we find an economically large and statistically significant result in two very different auction environments. After controlling for variables that could influence subjectsÕ bids such as differences in private values, cumulative earnings, and learning effects, the prices in the January markets were systematically higher than those in December. The results suggest that psychological factors may contribute to the well-documented January effect in empirical stock market data, a conclusion that clearly violates the efficient markets hypothesis.
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Selecting invalid instruments to improve Mendelian randomization with two-sample summary data
Mendelian randomization (MR) is a widely-used method to estimate the
causal relationship between a risk factor and disease. A fundamental part
of any MR analysis is to choose appropriate genetic variants as instrumental
variables. Genome-wide association studies often reveal that hundreds of
genetic variants may be robustly associated with a risk factor, but in some situations
investigators may have greater confidence in the instrument validity
of only a smaller subset of variants. Nevertheless, the use of additional instruments
may be optimal from the perspective of mean squared error even if
they are slightly invalid; a small bias in estimation may be a price worth paying
for a larger reduction in variance. For this purpose, we consider a method
for "focused" instrument selection whereby genetic variants are selected to
minimise the estimated asymptotic mean squared error of causal effect estimates.
In a setting of many weak and locally invalid instruments, we propose
a novel strategy to construct confidence intervals for post-selection focused
estimators that guards against the worst case loss in asymptotic coverage. In
empirical applications to: (i) validate lipid drug targets; and (ii) investigate
vitamin D effects on a wide range of outcomes, our findings suggest that
the optimal selection of instruments does not involve only a small number
of biologically-justified instruments, but also many potentially invalid instruments
Data for Towards a Low Pollution Future - Lessons Learnt from the Ban of Leaded Gasoline
1doi:10.25540/HXFN-68F