Genetics of psychiatric disorders in latino populations

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Genetics of psychiatric disorders in latino
populations

• Virginia Rodriguez Funes, MD, FACS
• El Salvador

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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.

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• 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.

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• 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.

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• 3. Key obstacles to mapping PD gene loci
• Ethiological heterogeneity
• Imprecision in the definition of affected
  phenotypes
• Uncertainty regarding mode of genetic transmission

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• Psychiatric investigators, health care providers
  and government officials have all identified
  ethnic disparities in mental health treatment as
  a significant US public health problems.

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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

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• 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.

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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.

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• 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.

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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

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• 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.

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• 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

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• All subjects affected and non-affected will
• Give samples of DNA
• MRI tests
• 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

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• 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.

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• 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.

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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?

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Second question

• How would you categorize the potential population
  to the sponsor, and the principal researchers.

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Third question

• Do you think the rational for population
  selection is free of bias (descrimination)?

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Fourth question

• How would you classify the risk of participation
  of this population?

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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?