Spurious association

One major concern of the association study is that spurious associations may occur if the genetic background in cases is different from that in controls. Genetic heterogeneity in a population can be a result of population structure and recent admixture. In this chapter, we review the problem of population structure, demonstrate how that structure affects association study, and discuss solutions to this problem. 

Subheading 3.4.2) can correct for spurious association. These methods were recommended to adjust for population stratification even when a genetically homogeneous population is used in association studies. 

Redden, D.T., and Allison, D.B. (2006) The effect of assortative mating upon genetic association studies spurious associations and population substructure in the absence of admixture. Behav. Genet. 36, 678-686. 

The recent emphasis on use of only family based association/linkage tests has ignored the readily available resource of case/control data (57), where sampling and then study of many thousands of samples are feasible with new techniques. Provided the patient and control groups are carefully matched for ethnicity, population stratification effects creating spurious associations are eliminated. The large collections of multiplex families now available for linkage studies in many complex diseases are obviously also a valuable resource for association screens (65,80). 

A review of the data generated in the last 4 years has amply described the continued efforts of the scientific community to monitor and understand true measles vaccine-associated adverse events (6). The rapidity and clarity of this same community s debunking of the spurious associations with Crohn s disease and autism suggests that those charged with vaccination programs have learned from past mistakes. 

Without considering the stability of a PM model in an independent sample, it is possible to be unaware of the fact that some factors represent spurious associations with the outcome because of noise in the data or multiple comparisons. Furthermore, minor changes in the data set may result in the selection of different covariates. This might leave one in a quandary as to which covariates actually are of predictive importance. When statistical significance is the sole criterion for... 

Such data is often not available in the field for patterns of disease in human populations, and thus spurious associations may be made when a cluster is encountered. In reality, it often is only due to chance, an event analogous to coin flipping and getting four heads in a row. 

Sample heterogeneity (population stratification) Study subjects come from diverse genetic backgrounds. The presence of sample heterogeneity can introduce spurious associations between disease and genetic markers. 

Careful delineation of the clinical cases. A specific defect or syndrome, if present, is very helpful. If the teratogen is associated only to one or a few specific birth defects, the possibility of a spurious association becomes smaller. In this meta-analysis, the malformations were variable with no specific trend apparent. 

Most of our subjects are middle to upper-middle class white infants, for whom socioeconomic status and quality of caregiving are at most only weakly associated with prenatal or postnatal blood lead levels (Bellinger et al, 1985b, 1986b). They do not display the typical association between demographic/ economic risk factors and increased lead exposure seen in most samples. As a consequence, the likelihood of observing a spurious association between elevated lead exposure and poor outcome is lower in this sample than it is in most samples recruited to study the developmental impact of lead. 

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