Genetics of psychiatric disorders in latino populations

1. Virginia RodriguezFunes, MD, FACS El Salvador Genetics of psychiatricdisorders in latino populations

2. 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.

3. Thisstudyproposesthesamplecollection, genotyping and analysisnecessarytolocalize genes thatcontributeto PD genesis and quantitativetraitsassociatedwith PD in thispopulation. • Thelongtermgoals, beyondthescope of thisstudy are to fine map and identifymutations in specific genes associatedwithlociidentified in thecourse of thiscurrentproject.

4. 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.

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

6. Psychiatricinvestigators, healthcareproviders and governmentofficialshaveallidentifiedethnicdisparities in mental healthtreatment as a significant US publichealthproblems.

7. 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

8. 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.

9. Howtoidentifyendophenotypes • 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.

10. 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.

11. Methodology • Local researchersfromMexico and Central Americawillbetrained in the US withspecifictoolsforaccuratepsychiatric diagnosis • Local researcherswillcollectthefamilies in 6 mesoamericancountries: recruiterswillidentify PD diagnosedsubjects in inpatient and outpatientunits in psychiatrichospitals and with media advertisement

12. 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.

13. 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

14. 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

15. Cellcultureswillbemaintained in this central bank in the US and willbemadeavailabletoqualifiedresearchers at theend of thisproject. Genes willbedissociatiedfrom ID. Familyrelationshipinformation, ethnicity, and allclinical and genotype data willbeincluded in thedatabase. DNA willbe placed in thepublicdomain, theywillbeavailabletoinvestigatorsto use in projectsthat are unrelatedtothepresentone and mayevenbeputtocommercial use.

16. Theparticipantswillbeinformed of thesepossibilities in thenarrativesummary and willbemadeawarethattheywillhave no rightstoanysubsequent use of thematerials.

17. 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?

18. Second question How would you categorize the potential population to the sponsor, and the principal researchers.

19. Third question Do you think the rational for population selection is free of bias (descrimination)?

20. Fourth question How would you classify the risk of participation of this population?

21. 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?