Abstract
During the initial stages of the genome revolution human genetics was hugely successful in discovering the underlying genes for monogenic diseases. Over 3,000 monogenic diseases have been discovered with simple patterns of inheritance. The unravelling and identification of the genetic variants underlying complex or multifactorial traits, however, is proving much more elusive. There have been over 1,000 significant variants found for many quantitative and binary traits yet they explain very little of the estimated genetic variance or heritability evident from family analysis. There are many hypotheses as to why this might be the case. This apparent lack of information is holding back the clinical application of genetics and shedding doubt on whether more of the same will reveal where the remainder of the variation lies. Here we explore the current state of play, the types of variants we can detect and how they are currently exploited. Finally we look at the future challenges we must face to persuade the human genome to yield its secrets.