been diagnosed with the disease under study, or have the trait under test; the controls, who are either known to be unaffected, or who have been randomly selected from the population. A difference in the frequency of an allele or genotype of the polymorphism under test between the two groups indicates that the genetic marker may increase risk of the disease or likelihood of the trait, or be in linkage disequilibrium with a polymorphism which does. Haplotypes can also show association with a disease or trait. One of the earliest successes in this field was finding a single base mutation in the non-coding region of the APOC3 gene (apolipoprotein C3 gene) that associated with higher risks of hypertriglyceridemia and atherosclerosis using a case-control design. One problem with the case-control design is that genotype and haplotype frequencies vary between ethnic or geographic populations. If the case and control populations are not well matched for ethnicity or geographic origin then false positive association can occur because of the confounding effects of population stratification. Family based designs Family based association designs aim to avoid the potential confounding effects of population stratification by using the parents or unaffected siblings as controls for the case (the affected offspring/sibling). Two similar tests are most commonly used, the transmission disequilibrium test (TDT) and haploid-relative-risk (HRR). Both measure association of genetic markers in nuclear families by transmission from parent to offspring. If an allele increases the risk of having a disease then that allele is expected to be transmitted from parent to offspring more often in populations with the disease. Quantitative trait association A quantitative trait (see quantitative trait locus) is a measurable trait that shows continuous variation, such as height or weight. Quantitative traits often have a 'normal' distribution in the population. In addition to the case control design, quantitative trait association can also be performed using an unrelated population sample or family trios in which the quantitative trait is measured in the offspring. Evidence Evidence of the association is based on MNAs that are usually based on studies that include large sample sizes like genome-wide association studies. With only little empirical data associating study results and study design, bias in genetic association studies are not well understood. Reporting outcomes Based on traits either continuous or binary, heritability (going from 0 to 1 with 0 meaning non-hertiable) outcomes are usually reported respectively by the proportion of phenotypic