Causation association

Diseased groups No extrapolations Susceptible groups Long-term, low-level effects Many covariates Minimal dose-response data Association vs. causation... 

Figure 49-10. Simplified scheme of the causation of malignant hyperthermia (MIM 145600). At least 17 different point mutations have been detected in the RYRl gene, some of which are associated with central core disease (MIM 117000). It is estimated that at least 50% of families with members who have malignant hyperthermia are linked to the RYRl gene. Some individuals with mutations in the gene encoding DHPR have also been detected it is possible that mutations in other genes for proteins involved in certain aspects of muscle metabolism will also be found.

Hudson, Christopher G., Socioeconomic Status and Mental Illness Tests of the Social Causation and Selection Hypotheses , American Journal of Orthopsychiatry 75, no. 1 (2005) 3-18 The Humble Humbug , The Lancet 2 (1954) 321 Hunter, Aimee M., Andrew F. Leuchter, Melinda L. Morgan and Ian A. Cook, Changes in Brain Function (Quantitative EEG Cordance) During Placebo Lead-in and Treatment Outcomes in Clinical Trials for Major Depression , American Journal of Psychiatry 163, no. 8 (2006) 1426-32 Hyland, Michael E., Do Person Variables Exist in Different Ways , American Psychologist 40 (1985) 1003-10 Hypericum Depression Trial Study Group, Effect of Hypericum Perforatum (St John s Wort) in Major Depressive Disorder A Randomized Controlled Trial , Journal of the American Medical Association 287 (2002) 1807-14... 

To obtain the mass emissions of pollutants from e-waste recycling processes, it is essential that the inputs of pollutants are truly e-waste related. To fulfill this requirement, a causal analysis is desirable. However, the concept of causation is rather problematic because causal mechanisms are complex [26]. Nonetheless, we are compelled to identify causes, in an attempt to minimize the uncertainties associated with our estimates. In this chapter, the strict empiricist, David Hume s empirical criterion, was adopted. This approach requires only a combination of (1) e-waste processing and environmental pollution are associated in space and time (contiguity) (2) e-waste processing precede to environmental pollution (temporal succession) and (3) e-waste processing is always conjoined with environmental pollution (consistent conjunction). These are always the cases judged from a number of previous studies [6, 27-35]. 

In addressing the question of how income inequality is linked to population health, Muntaner and Lynch (1999) identified two strands of causation, thus combining the approaches of Kaplan and Wilkinson. First, they claim that income inequality is associated with a set of social processes and economic policies that systematically under-invest in physical and social infrastructure (e.g. education). Secondly, large disparities in income distribution may have direct consequences on people s perceptions of their relative place in the social environment, which leads to behavioral and cognitive states that influence health. 

The targets for clinical pharmacogenomic associations are not necessarily the same as those for genetics. A gene may have a role in the response to antidepressant treatment and not be necessarily involved in the causation of the disorder. Biological systems that are thought to be involved in the response to antidepressant treatment include the following ... 

Feinstein (1979) has provided a fine discussion of the difference between correlation (or association of variables) and causation. 

Feinstein, A.R. (1979). Scientific standards vs. statistical associations and biological logic in the analysis of causation. Clin. Pharmacol. Ther. 25 481-492. 

A demonstration of this nature is said to establish an association between the factor and the excess cancers. Two events - in this case the factor and the excess cancers - are said to be associated when they occur together more frequently than they should if chance alone were operating. We need to turn to statisticians to figure out whether the odds are greater than those associated with a chance occurrence. Association is not causation, but demonstrating that an association exists gets the epidemiologist part of the way to an answer. 

Note also that, even if some evil epidemiologists could undertake such an experiment in humans, there is virtually no way two human populations could be assembled and matched in the way lab animal populations can be matched, so that causation would remain difficult for the epidemiologist to establish. This matching problem begins to explain why there is much distance to travel even after an association is demonstrated. 

Return now to a point made early in this section. Statistical associations, the existence of which cohort and case-control studies can reveal to us, are not, of themselves, evidence of causation. If found, and even if they are strong - large relative risk or odds-ratio - they do not establish that the phenomena being investigated, the phenomena that are associated (disease and some exposure or other factor) are causally related. To see most easily why this is so, it is best to examine the difficulties that need to be overcome to move from association to any conclusion about the existence of a causal link. 

Another type of biological evidence that supports a case for causation derives from experimental work with animals if the substance under consideration is carcinogenic in animals, associations seen in epidemiology studies become biologically supportable. Sometimes it is possible to conduct a study after intervening to remove the suspect substance if risk declines following such an intervention, the case for causation strengthens (recall Pott s chimney sweeps). 

Several theories of incident causation exist and each has associated investigation techniques. Incident investigators use their judgment to make adaptations to selected techniques based on the size and complexity of the investigation effort. Judgment based on knowledge and experience is important in determining how and why an incident occurred. 

Theoretical incident concepts and associated models have evolved from investigations into the how and why of case histories. Resulting insights have made it possible to better explain and understand incident causation. There are many other incident causation theories besides the ones presented in this chapter, such as the Process Theory. (See the additional references for this chapter.) Key theories on incident causation discussed in this overview are ... 

Bradford Hill, A. 1965. The environment and diseases association or causation Proc. R. Soc. Med. 58 295-300. BUA. 2007. The Advisory Committee on Existing Chemicals of Environmental Relevance (BUA) website http /www.gdch.de/taetigkeiten/bua e.htm... 

Lucas, R. M. and McMichael, A. J. 2005. Association or causation evaluating hnks between environment and disease. Bull. WHO 83 792-795. http //www.who.int/bulletin/volumes/83/10/792.pdf NCT. 2007. The National Center for Toxicogenomics (NCT) website. http /www.niehs.nih.gov/nct/office.htm OECD. 2002. 3.3 Guidance for the use of structure-activity relationships (SARs) in the HPV chemicals programme. In Manual for Investigation of HPV Chemicals. Paris OECD. http /www.oecd. org/dataoecd/60/24/1947517.pdf... 

When a covariate is affected by the treatment either through direct causation or through association with another factor, the adjustment may hide or exaggerate the treatment effect. It therefore makes the treatment effect difficult to interpret. ... 

Berkovitch, M., Pope, E., Phillips, J., and Koren, G. (1995) Pemoline-associated fulminant liver failure testing the evidence for causation. Clini Pharmacol Ther 57 696—698. 

There are reports of an association between low fish consumption and increased prevalence of depression (Hibbelin, 1998). Some studies have found a reduced level of omega-3 fatty acids in depressed patients. It has also been speculated that EFAs have a role in the causation of schizophrenia and, more recently, ADHD and behavioral problems (Stevens et ah, 1996 Burgess et ah, 2000). 

Nevertheless, depressive episodes among alcohol-dependent men and women are heterogeneous in terms of both causation and clinical course. Studies have shown differences between patients with the onset of major depression before alcohol dependence or during a long abstinence period (i.e., independent major depression) versus those who experience depressive symptoms only in association with alcohol use ( 34). Specifically, the former are more likely to ... 

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