BDNF genetic variants are associated with onset age of familial Parkinson disease: Gene PD Study

Abstract

When more really means more: WGS standards and quality control Next-generation sequencing (NGS) is reshaping the landscape of modern genetic diagnostic laboratories and their operational standards. NGS is gradually replacing the single-gene Sanger sequencing with targeted multigene panel-based resequencing for genes with variants implicated in any number of common diseases, from cardiovascular or neurological disorders to cancers or drug treatment response. Further advances in technology are positioning whole exome and ultimately whole genome sequencing (WES and WGS) for common diagnostic use. In a rapidly changing environment, quality control considerations are crucial. In this issue, Stephan White et al. (Hum Mutat 38: 912-921, 2017) discuss the critical steps that are required to properly perform WGS. They emphasize the key differences between WGS and WES, the important variables that need to be taken into serious consideration when performing NGS for both germline and somatic variants, the necessary quality control measures to monitor the entire process, and the standard operation procedures to ensure that NGS services will always be provided in a standardized manner. It is obvious that further technological advances in massively parallel DNA sequencing technology, accompanied by concomitant price reductions, will make WES and WGS more affordable and hence easier to become the ultimate genetic test in molecular diagnosis. Such advances must undoubtedly be accompanied with the necessary health technology assessment and economic evaluation analyses, demonstrating that such approaches are indeed cost-effective so that they can be adopted sooner and, most importantly, are covered by national healthcare systems. The points discussed in White et al., combined with those from recently published guidelines for variant calling, genomic databases, genomic data sharing and translational tools, should facilitate implementation of NGS services into the molecular diagnostic setting for routine clinical care.

No Association between Brain-Derived Neurotrophic Factor G196A Polymorphism and Clinical Features of Parkinson's Disease

“…Also, according to our data, the G196A polymorphism did not seem to modify motor and nonmotor clinical features and treatment complications in PD patients. It did not influence age of onset and was uniformly distributed among sporadic and familial cases, which is in contrast to the report by Karamohamed et al [27] which showed the G196A polymorphism was associated with an older onset of the disease. Similar to our study, a meta-analysis did not support the hypothesis that this variation was a risk factor for idiopathic PD [11].…”

Nuclear receptor NR4A2 IVS6 +18insG and brain derived neurotrophic factor (BDNF) V66M polymorphisms and risk of Taiwanese parkinson's disease

“…These results suggest that the genotype and allele frequencies of this polymorphism differ between ethnics. Homozygosity M/M for the BDNF V66M variant associated with a 5.3-year older onset age was shown recently in a large cohort of familiar PD [Karamohamed et al, 2005]. However, in the present study, the onset age of Taiwanese PD is not influenced by BDNF V66M.…”

BDNF polymorphism associates with decline in set shifting in Parkinson's disease

“…However, these studies are sparse and have provided conflicting results. The BDNF Met/Met genotype was, for instance, associated with a higher risk of developing dyskinesias earlier in the course of treatment with dopaminergic agents (Foltynie et al, 2009) and an older age of onset (Karamohamed et al, 2005), whereas other studies were unable to find any association with clinical characteristics, including dyskinesias or age at onset (Gao et al, 2010;Karakasis et al, 2011). As these studies used different outcome measures, have individually not been replicated, and were all cross sectional, it is difficult to establish the exact role, if any, of BDNF in explaining the clinical variability of PD.…”