The genetics of kidney transplantation

Over the last decade, the search for gene variants with the potential to influence transplant outcomes or predispose individuals to host-recipient-related phenotypes has generated a considerable number of studies with conflicting results. Thousands of genotypes have been associated with complex traits related to transplant medicine, including acute rejection, immunosuppressive drug metabolism and side effects, infections, long-term outcomes, and cardiovascular complications. However, these efforts have given disappointing results, both in terms of gaining understanding of the biological basis of disease and in patient management. The methodological weaknesses that constitute the major limitations of most of these studies have been discussed widely. A new generation of approaches is needed to understand the relationship between gene variants and complex kidney transplantation traits. These approaches should be global, to generate original pathophysiological hypotheses, and should rely on advanced genomic tools, including Genome Wide Association studies and Whole Genome Sequencing technologies. Such enterprises will only be successful with the creation of international consortiums that connect partners in clinical, industrial, and academic transplant medicine.