Transcript Genetics of psychiatric disorders in latino populations

Virginia Rodriguez Funes, MD, FACS
El Salvador
Background
The Latin American population it is now the
largest single ethnic group in the United
States, which makes it a timely population for
genetic study,
 It has been largely untapped in previous
genetic studies of PD and,
 It has more individuals per family than other
ethnic groups, and has genetic isolates which
may aid in the fine-mapping of susceptibility
loci identified from initial genome screens.

This study proposes the sample collection,
genotyping and analysis necessary to
localize genes that contribute to PD genesis
and quantitative traits associated with PD in
this population.
 The long term goals, beyond the scope of
this study are to fine map and identify
mutations in specific genes associated with
loci identified in the course of this current
project.

1. Psychiatric disorders (PD):
 Affect quality of life for the individuals and
families
 Contribute to high annual public health costs
 Are of high prevalence in all populations
studied
2. Difficulty finding genetic loci that are involved
in PD derived from the complex nature of
the illness. No study has shown
predominant linkage to just one site in their
sample, even when the sample is drawn
from a more homogenous population.
3. Key obstacles to mapping PD gene loci:
 Ethiological heterogeneity
 Imprecision in the definition of affected
phenotypes
 Uncertainty regarding mode of genetic
transmission
Psychiatric investigators, health care
providers and government officials have
all identified ethnic disparities in mental
health treatment as a significant US
public health problems.
Rationale
1. To overcome this obstacle:
Collect samples from very large families,
consistingly of rigorously diagnosed PD
individuals, drawn from genetically
homogeneous populations.
2. Some studies have shown recent advances
in identifying genes for specific PD in very
narrow diagnostic classification. The PD
studied in this project is currently at a
similar stage
The researchers project enhanced potential
to identify genes involved in the
pathogenesis of PD in the Latino
population, by defining endophenotypes
and quantitative traits that are associated
with PD in the pedigrees which will
constitute this study.
How to identify
endophenotypes

By collecting neuropsychological data
on probands and their families, with an
extension to second and third degree
relatives, in a subset of X number of
pedigrees.
For a cognitive measure or any marker to be
considered, an endophenotype must
show:
 High heritability
 Association with the illness
 Presence independent of the clinical state
 Cosegregate with the illness within a
family
 Non-affected family members must show
impairment on this measure.
Methodology
Local researchers from Mexico and Central
America will be trained in the US with
specific tools for accurate psychiatric
diagnosis
 Local researchers will collect the families in
6 mesoamerican countries:
recruiters will identify PD diagnosed
subjects in inpatient and outpatient units in
psychiatric hospitals and with media
advertisement

Identified patient vital data will be collected in
an Excel database, then will prioritize those
under 40 years of age. Then will contact
them and obtain preliminary informed
consent, to get data, such as, presence of
siblings with the illness and verification that
four grandparents are from mesoamerican
ancestors. When the family meets the
inclusion criteria and agrees to participate,
the psychiatric diagnostic tools will be used
on the patient and the affected sibling and
neuropsychological assessment will be
conducted in all members of the family.
The ideal family to be recruited would be:
 PD sibling pairs
 Parents
 An average of two unaffected siblings.
Unaffected or affected siblings can be from
age 15 up.
X number of pedigrees averaging 20 subjects
per pedigree
All subjects affected and non-affected will:
1. Give samples of DNA
2. MRI tests
3. Perform clinical and neuropsychological
testing.
 Gene samples will be sent to a central
Universities in the US and analyzed with
special softwares
 Then, gene samples will be banked in a
central gene bank in the US and will be
shared with other researchers as an
unfinishible source of DNA
Cell cultures will be maintained in this central
bank in the US and will be made available
to qualified researchers at the end of this
project. Genes will be dissociatied from ID.
Family relationship information, ethnicity,
and all clinical and genotype data will be
included in the database.
DNA will be placed in the public domain, they
will be available to investigators to use in
projects that are unrelated to the present
one and may even be put to commercial
use.
The participants will be informed of these
possibilities in the narrative summary
and will be made aware that they will
have no rights to any subsequent use of
the materials.
First question
Do you find any ethical issues with the
proposed logic for overcoming the failures
in identifying genes loci associated with the
pathogenesis of PD?
Second question
How would you categorize the potential
population to the sponsor, and the
principal researchers.
Third question
Do you think the rational for population
selection is free of bias
(descrimination)?
Fourth question
How would you classify the risk of
participation of this population?
Fifth question
Do you think the whole study shoud be
adjusted to the Universal Declaration of
Genetic data recollection?
How would you classify the autonomy of
this population based on the way they
were identified and recruited?