Genetic Modifiers in Neurodegeneration

Purpose of ReviewTo review the evidence for genetic modifier effects in the neurodegenerative diseases: Huntington's disease (HD), frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and Parkinson's disease (PD).Recent FindingsIncreasingly, we understand human disease genetics less through the lens of single-locus/single-trait effects, and more through that of polygenic contributions to disease risk. In addition, specific examples of genetic modifier effects of the chromosome 7 gene TMEM106B on various target genes including those causal for Mendelian classes of FTLD-GRN and c9orf72-have emerged from both genetic cohort studies and mechanistic examinations of biological pathways.SummaryHere, we summarize the literature reporting genetic modifier effects in HD, FTLD, AD, and PD. We further contextualize reported genetic modifier effects in these diseases in terms of insight they may lend to the concept of a polygenic landscape for the major neurodegenerative diseases.