Phenotypic characterization and genealogical tracing in an Afrikaner schizophrenia database

Abstract

Founder populations hold tremendous promise for mapping genes for complex traits, as they offer less genetic and environmental heterogeneity and greater potential for genealogical research. Not all founder populations are equally valuable, however. The Afrikaner population meets several criteria that make it an ideal population for mapping complex traits, including founding by a small number of initial founders that likely allowed for a relatively restricted set of mutations and a large current population size that allows identification of a sufficient number of cases. Here, we examine the potential to conduct genealogical research in this population and present initial results indicating that accurate genealogical tracing for up to 17 generations is feasible. We also examine the clinical similarities of schizophrenia cases diagnosed in South Africa and those diagnosed in other, heterogeneous populations, specifically the US. We find that, with regard to basic sample descriptors and cardinal symptoms of disease, the two populations are equivalent. It is, therefore, likely that results from our genetic study of schizophrenia will be applicable to other populations. Based on the results presented here, the history and current size of the population, as well as our previous analysis addressing the extent of background linkage disequilibrium (LD) in the Afrikaners, we conclude that the Afrikaner population is likely an appropriate founder population to map genes for schizophrenia using both linkage and LD approaches.

Cannabis and other variables affecting age at onset in a schizophrenia founder population

“…The findings of this research have thus far has been published elsewhere. 4,5 The clinical database of this ongoing study contains information obtained from the Diagnostic Interview for Genetic Studies (DIGS), a chronological summary report of each subject and other sources of information. 4 This database provided the following information for 341 subjects included in the study thus far:…”

Elucidating the genetic architecture of familial schizophrenia using rare copy number variant and linkage scans

“…To understand the genetic architecture of familial SCZ and the pattern of transmission of rare risk alleles in affected families, we combine high-resolution linkage analysis with studies of fine-level chromosomal variation in families recruited from the Afrikaner population in South Africa, a genetically and environmentally homogeneous population who have descended from mostly Dutch immigrants who settled in South Africa beginning in 1652 (20). In addition to the genetic homogeneity, the Afrikaners are valuable for genetic studies because they present a close-knit family structure and offer the potential to perform detailed genealogical analysis, which affords reliable discrimination of familial and nonfamilial forms of the disease and facilitates family-based genetic studies.…”

Advancing paternal age at birth is associated with poorer social functioning earlier and later in life of schizophrenia patients in a founder population

“…(Karayiorgou et al, 2004) These subjects form part of a cohort of cases enrolled in ongoing genetic research, being conducted collaboratively by the Department of Psychiatry, University of Pretoria and the Laboratory for Human Genetics, Columbia University, New York.…”

“…The Afrikaner population in South Africa is a genetically and environmentally homogeneous population who have descended from mostly Dutch immigrants who settled in South Africa from 1652 onwards (Karayiorgou et al, 2004). In addition to the genetic homogeneity, the Afrikaners are valuable for genetic studies because they present a close-knit family structure and offer the potential to perform detailed genealogical analysis, which affords reliable discrimination of familial and non-familial (sporadic) forms of the disease (Xu et al, 2012).…”

“…The criteria used for being classified as an Afrikaner included: Afrikaans language, typical Afrikaans surname of both parents and grandparents on the paternal and maternal side, and genealogical tracings by a genealogist (Karayiorgou et al, 2004) …”