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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses.

Rare sequence variants may be important in understanding the biology of common diseases, but clearly establishing their association with disease is often difficult. Association studies of such variants are becoming increasingly common as large-scale sequence analysis of candidate genes has become feasible. A recent report suggested SLITRK1 ( Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS). The statistical evidence for this suggestion came from association analyses of a rare 3'-UTR variant, var321, which was observed in two patients but not observed in more than 2000 controls. We genotyped 307 Costa Rican and 515 Ashkenazi individuals (TS probands and their parents) and observed var321 in five independent Ashkenazi parents, two of whom did not transmit this variant to their affected child. Furthermore, we identified var321 in one subject from an Ashkenazi control sample. Our findings do not support the previously reported association and suggest that var321 is overrepresented among Ashkenazi Jews compared with other populations of European origin. The results further suggest that overrepresentation of rare variants in a specific ethnic group may complicate the interpretation of association analyses of such variants, highlighting the particular importance of precisely matching case and control populations for association analyses of rare variants.[1]


  1. Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses. Keen-Kim, D., Mathews, C.A., Reus, V.I., Lowe, T.L., Herrera, L.D., Budman, C.L., Gross-Tsur, V., Pulver, A.E., Bruun, R.D., Erenberg, G., Naarden, A., Sabatti, C., Freimer, N.B. Hum. Mol. Genet. (2006) [Pubmed]
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