Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, all studies have been performed in just one population at the time. Here we performed the first large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases, and 2,458,063 controls including individuals of European, East Asian, Latin American, and African ancestry. In a single joint meta-analysis, we identified 78 independent genome-wide significant loci including 12 potentially novel loci (MTF2, RP11-360P21.2, ADD1, SYBU, IRS2, USP8:RP11-562A8.5, PIGL, FASN, MYLK2, AJ006998.2, Y_RNA, PPP6R2) and finemapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 23 genes near these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.

Background: Late onset cases of Huntington disease (HD), with onset ≥60 years, account for up to 20% of HD cases worldwide. Clinical features include mild motor dysfunction with slow progression and cognitive impairment, frequent absence of family history and low number of CAG repeats. The clinical and molecular features of late onset HD is still understudied in Latin America. Objectives: To describe the clinical and molecular characteristics of late onset HD in a Peruvian cohort. Methods: An observational study was carried out by reviewing the HD registry at the Neurogenetics Research Center-INCN from 2000 to 2014. Genotyping of HTT gene was confirmed using standard PCR and PAGE in accordance to protocols previously established.Results: Thirty-one late onset HD cases from 27 pedigrees were identified (9.42% of total HD cases, n = 329), 51.61% were male. Mean age at onset was 64.1 ± 4.2 and CAG repeats mean was 42.5 ± 2.5. We did not find significant correlation between age at onset and CAG repeats. 33.3% of cases were traced back to Cañete valley. Twenty-two cases had a positive family history, 14 of them with paternal transmission. Choreic movements and cognitive impairment were the main existing manifestations reported in this cohort, with lower frequency of psychiatric disturbances. Conclusions: This report of late onset HD affected individuals shows a mild phenotype expression of the disease, associated with low range of CAG repeats and up to 30 % of cases with absence of clear family history. Cañete valley remains the region with more cases.

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Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients from two Latin American countries were analysed, being 16 families from Brazil (29 patients) and 21 families from Peru (27 patients) as well as 49 healthy individuals from Indigenous Quechua population and 51 healthy Brazilian individuals. Four polymorphic markers spanning a region of 5.2 cM harbouring the ATTCT expansion were used to define the haplotypes, which were genotyped by different approaches. Our data have shown that 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both groups are not statistically different from Quechua controls (57%), but they are statistically different from Brazilian controls (12%) (p < 0.001). The most frequent expanded haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients with SCA10. These findings bring valuable evidence that ATTCT expansion may have arisen in a Native American chromosome.

Neurogenetics, the science that studies the genetic basis of the development and function of the nervous system, is a discipline of recent development in Peru, an emerging Latin American country. Herein, we review the clinical, scientific and ethical aspects regarding the development of this discipline, starting with the first molecular diagnosis of neurogenetic diseases, to family and population-based genetic association studies. Neurogenetics in Peru aims to better explain the epidemiology of monogenic and complex neurodegenerative disorders that will help in implementing public health policies for these disorders. The characterization of Peru and its health system, legal issues regarding rare diseases and the historical milestones in neurogenetics are also discussed.Keywords Bioethics . Neurogenetics . Peru . Public policies Neurogenetics in Latin AmericaNeurogenetics studies the genetic basis of the nervous system, exploring its function and development for a better understanding of neurological disorders (Trelles and De los Angeles 1989; Vaillant 2000). Roughly, 80 % of the transcriptome is expressed in the human brain (Hawrylycz et al. 2012), where resident cell types show specific neuroanatomical distributions and molecular signatures that can be associated with neurodegenerative and neuropsychiatric disorders (Lotan et al. 2014;Miller et al. 2010). The development of novel genomic technologies, large-scale genome databases and global collaborations have revolutionized our understanding of the molecular basis and diagnostic and therapeutical approaches in many neurological disorders, especially within highly polygenic disorders (McCarroll et al. 2014).