RT Journal Article
SR Electronic
T1 Human-genome gut-microbiome interaction in Parkinson’s disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.21.427679
DO 10.1101/2021.01.21.427679
A1 Zachary D. Wallen
A1 William J. Stone
A1 Stewart A. Factor
A1 Eric Molho
A1 Cyrus P. Zabetian
A1 David G. Standaert
A1 Haydeh Payami
YR 2021
UL http://biorxiv.org/content/early/2021/01/22/2021.01.21.427679.abstract
AB The causes of complex diseases remain an enigma despite decades of epidemiologic research on environmental risks and genome-wide studies that have uncovered tens or hundreds of susceptibility loci for each disease. We hypothesize that the microbiome is the missing link. Genetic studies have shown that overexpression of alpha-synuclein, a key pathological protein in Parkinson’s disease (PD), can cause familial PD and variants at alpha-synuclein locus confer risk of idiopathic PD. Recently, dysbiosis of gut microbiome in PD was identified: altered abundances of three microbial clusters were found, one of which was composed of opportunistic pathogens. Using two large datasets, we show that the overabundance of opportunistic pathogens in PD gut is influenced by the host genotype at the alpha-synuclein locus, and that the variants responsible modulate alpha-synuclein expression. This is the first demonstration of interaction between genetic factors in the human genome and the dysbiosis of gut microbiome in PD.Competing Interest StatementThe authors have declared no competing interest.