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Introduction 107

Table 6.2 An Overview of Published Association Studies for Candidate
Genes and Neurological Diseases in Latin American Countries (cont.)
Disease Country Genes Reference
Attention deficit and Brazil GAD1 Bruxel et al. (2016)
hyperactivity disorder
Attention deficit and Brazil SNAP25, NOS1 Salatino-Oliveira et al.
hyperactivity disorder (2016a)
Attention deficit and Brazil SYT1 Cupertino et al. (2017)
hyperactivity disorder
Ischemic stroke Mexico MTHFR Isordia-Salas et al. (2010)
Parkinson’s disease Colombia A2M, ACE, BDNF, Benitez et al. (2010)
COMT, MAPT,
SLC6A3,
SLC6A4, UCHL1
Parkinson’s disease Colombia LRRK2 (Mutations) Duque et al. (2015)

LRRK2, among others) for hereditary forms of NDs (Duque et al., 2015; Lalli
et al., 2014; Muchnik et al., 2015). In Colombia, there is the largest familial clus-
ter of Alzheimer’s disease around the world, and it is caused by a mutation in the
PSEN1 gene (p.E280A) that leads to an autosomal-dominant hereditary type of
early-onset Alzheimer’s disease (Sepulveda-Falla et al., 2012). Venezuela has the
largest familial cluster of Huntington’s disease, caused by a polyglutamine muta-
tion in the HTT gene (Castilhos et al., 2016). In a small city from the northwest-
ern of Colombia, there are around 25 multigenerational families affected with
Huntington’s disease (De Castro and Restrepo, 2015). These clusters of families
with genetic disorders are usually the result of high levels of consanguinity, in
the context of genetic isolates, which are quite useful for studying major genes
(Dahdouh et al., 2016). Some of these isolated populations have been studied
in genome-wide linkage and association studies (carried out in collaboration
with research groups in high-income countries) focused on several NPDs, such
as ADHD (Arcos-Burgos et al., 2010), bipolar disorder (Kremeyer et al., 2010),
and Tourette syndrome (Scharf et al., 2013). Some epileptic syndromes, such
as juvenile myoclonic epilepsy, have a well-defined genetic background. Studies
have shown that mutations in EFHC1 gene are found in 9% of consecutive juve-
nile myoclonic epilepsy cases from neurology clinics in Mexico and Honduras
(Medina et al., 2008).
There are very few studies that have analyzed DNA methylation markers for
NDs in Latin America (Hernandez et al., 2014). Several meta-analyses for can-
didate genes and telomere length have been carried out in Latin American
countries for AD, PD, and stroke (Forero et al., 2009; Forero et al., 2016a,b;
Gonzalez-Giraldo et al., 2016a), in addition to computational analyses of the
functional pathways for candidate genes for some of these disorders (Forero
et al., 2016c; Guio-Vega and Forero, 2017).