Segregation analysis of Parkinson disease

Parkinson disease (PD) is a prevalent movement disorder of unknown cause wh ose incidence rises with increasing age. Nearly 20% of PD is familial, a sm all subset of which exhibits autosomal dominant transmission. However, in m ost families, the inheritance is not clear, To determine the most likely mo de of inheritance of PD, we performed complex segregation analyses using ki ndreds of 136 PD patients randomly ascertained from a clinic population, Th e hypotheses of a nontransmissible environmental factor, no major gene or t ype (sporadic), and all Mendelian inheritance (dominant, recessive, additiv e, decreasing) were rejected (P <0.001). Familial clustering of PD in this data set is best explained by a rare familial factor which a) is transmitte d in a non-Mendelian fashion, and b) influences the age at onset of PD, If confirmed, our results have immediate implications in gene-mapping studies which often search for genes that behave in a Mendelian fashion that affect susceptibility rather than age at onset and long term implications in unde rstanding the pathogenesis of PD. Am. J. Med. Genet. 80:410-417, 1998. (C) 1998 Wiley-Liss, Inc.