A team of scientists from the Institute of Human Genetics of the GSF Research Center, the Technical University of Munich and the Max Planck Institute for Psychiatry have now identified risk factors which are involved in the development of Restless Leg Syndrome.

The patients suffer from an urge to move and paresthesia in the legs in the evening and during the night which can only be relieved by moving or walking around. The consequence may be severe sleeping disorders and chronic sleep loss. The frequency of RLS increases with age: up to ten per cent of over 65 year olds are affected, albeit in very different forms though hildren can also contract the disease.

The cause of RLS has so far been completely unknown. More than half of all RLS patients report about other family members who are also affected, so that a genetic component was assumed to be involved in the development of the disease at an early stage. Various groups of scientists have been looking for the genes which might play a role in RLS for years.

Under the guidance of Dr. Juliane Winkelmann and Professor Thomas Meitinger DNA chips were used which make it possible to determine 500,000 of the most common variants of the human genome. The distribution of the variants between 400 RLS patients and 1600 test subjects from the normal population was measured. This genome-wide comparison of frequent variants – also referred to as genome-wide association study – is one of the highlights of genome research this year.

Groups of scientists from Germany, Austria and Canada were involved. In all more than 1500 RLS patients and 2500 test subjects from the KORA Study of the GSF, which is conducted by Professor Erich Wichmann, participated in the study.

The genotyping platform at the GSF was partly funded by the National Genome Research Project (NGFN).

The function of the identified genes MEIS1, BTBD9 and LBXCOR1 surprised everybody involved: they are genes which are known in connection with the embryonic development of an organism. During this activity phase they are involved in the pattern formation of the extremities and the central nervous system. The role of these genes in adults will now have to be examined in greater detail.

How soon the knowledge about the genetic risk factors can be implemented in innovative new therapeutic concepts, remains to be seen. In any case new ways have now been opened up for the elucidation of the whole range of genetic and non-genetic causes of this disease. This offers researchers completely new perspectives for gaining an understanding of the cell-biology involved in the development of RLS.

Winkelmann, J. et al. (2007): Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nature Genetics (in press) (doi:10.1038/ng2099).