Genetic variation in DNA sequence influences risk of developing many diseases. Early studies investigated genetic variations underlying rare conditions that showed clear Mendelian segregation patterns through families (e.g. Huntington’s disease 1, cystic fibrosis 2); they were very successful in locating these genetic variations because they carried a 100% risk - and were the sole cause - of the disease. However, the search for genetic variants that underlie common ‘complex diseases’ (e.g. diabetes, cardiovascular disease, many cancers) has proven much more difficult. This is because each variant is only one of many genetic and environmental causal factors, each of which are neither necessary nor sufficient to individually cause the disease. Thus, they predispose to – rather than directly result in - its development. Finding those variants is important, because even a variant that results in a low increased RELATIVE RISK (see Glossary, Box 1) of a common condition may still have major public health importance in terms of the number of people affected because of it; moreover, such findings can uncover novel causal pathways worthy of further exploration.
