Population stratification in European South-American subjects and its importance to psychiatric genetics research in Brazil

Estratificação populacional em sul-americanos de origem européia e sua importância para a pesquisa genética psiquiátrica no Brasil

LETTERS TO THE EDITORS

Population stratification in European South-American subjects and its importance to psychiatric genetics research in Brazil

Estratificação populacional em sul-americanos de origem européia e sua importância para a pesquisa genética psiquiátrica no Brasil

Dear Editors,

It is really very exciting to know that another Brazilian group is working with molecular investigation in the field of psychiatric genetics.¹ When we decided to write a paper about the particularities, advantages and difficulties of conducting psychiatric genetic studies in the Brazilian population, we were aware of the possible biases of a narrative review.² However, that kind of approach seemed to be a more appropriate method in terms of our proposal because we believe that, by describing the history, development, and management of psychiatric genetic investigations in Brazil, we would be contemplating several contextual, cultural and political aspects and integrating different and independent fields of research in order to acquire a wider and multidisciplinary view of the subject at hand.

There is also another important point raised by Salum et al.¹ that needs to be addressed. Differently from what they claim, the use of "more homogenous samples like the Caucasians" does not "avoid stratification" in association studies on complex disorders such as neuropsychiatric disorders.²

Nowadays, it is well known that even when studying samples from a specific continental population such as the European, ethnic stratification can produce false associations at markers whose frequency differs across subpopulations.³ For example, in a recent whole genome association study of rheumatoid arthritis in European Americans, markers in the LCT and IRF4 genes could have been falsely implicated as being associated with the disease had no control method been applied to for the population's stratification.⁴ Certain studies have suggested that angiotensin I converting enzyme (ACE) gene polymorphism is associated with an increased risk of late onset Alzheimer's disease. However, when studying this, Panza et al. have found inconsistent findings within European studies.⁵ Interestingly, there is a statistically significant decreasing trend of the ACE*I/*D genotype frequency from northern to southern regions of Europe, which may contribute to explain the different patterns of associations found between such polymorphism and Alzheimer's disease across Europe.⁵ Recent investigations have suggested that genetic association studies in European Americans should use ancestry informative markers for examining north-south, Ashkenazi Jewish, and Irish ancestry.³

Several statistical methods have been developed to control for population stratification. Some studies have proposed that, considering that a small number of candidate markers may not be sufficiently informative and that genotyping a large number of markers can be expensive, the use of microarrays for ancestry estimation and correction has to be considered as a valuable tool when attempting to identify genes for complex traits through association studies involving European and European American populations. However, while studying subjects from European ancestry in Rio Grande do Sul, which is also Mr. Salum and his colleagues´ home state, a group of Brazilian researchers found a hidden ethnic admixture and proposed an interesting and cheap genomic control that can be used at the individual level, thus correcting for stratification by removing certain individuals from the sample without losing any statistical power due to statistical corrections.⁶

Quirino Cordeiro, Homero Vallada

Program of Genetics and Pharmacogenetics, Department

and Institute of Psychiatry, Universidade de São Paulo (USP)

Medical School, São Paulo (SP), Brazil

Bruno Rezende Souza, Humberto Correa, Marco Aurélio Romano-Silva

Department of Mental Health, Medical School,

Universidade Federal de Minas Gerais (UFMG),

Belo Horizonte (MG), Brazil

Camila Guindalini

Interdisciplinary Laboratory of Clinical Neuroscience,

Department of Psychiatry, Universidade Federal de São Paulo

(UNIFESP), São Paulo (SP), Brazil

Mara Helena Hutz

Department of Genetics, Universidade Federal do Rio

Grande do Sul (UFRGS), Porto Alegre (RS), Brazil

Click to extend

• 1. Salum GA, Blaya C, Segal J, Manfro GG, Leistner-Segal S. Emerging research groups in Brazilian psychiatric genetic studies. Rev Bras Psiquiatr. In press 2009.
• 2. Cordeiro Q, Souza BR, Correa H, Guindalini C, Hutz MH, Vallada H, Romano-Silva MA. A review of psychiatric genetics research in the Brazilian population. Rev Bras Psiquiatr 2009;31(2):154-62.
• 3. Seldin MF, Price AL. Application of ancestry informative markers to association studies in European Americans. PLoS Genet 2008;4(1):e5.
• 4. Tian C, Plenge RM, Ransom M, Lee A, Villoslada P, Selmi C, Klareskog L, Pulver AE, Gregersen PK, Seldin MF. Analysis and application of European genetic substructure using 300K SNP information. PLoS Genet 2008;4(1):e4.
• 5. Panza F, Solfrizzi V, D'Introno A, Colacicco AM, Capurso C, Capurso A, Kehoe PG. Shifts in angotensin I converting enzyme insertion allele frequency across Europe: implications for Alzheimer's disease risk. J Neurol Neurosurg Phychiatry 2003;74(8):1159-61.
• 6. Zembrzuski VM, Callegari-Jacques SM, Hutz MH. Application of an African Ancestry Index as a genomic control approach in a Brazilian population. Ann Hum Genet 2006;70(6):822-8.

Publication Dates

• Publication in this collection
  22 Mar 2010
• Date of issue
  Mar 2010