NEALE, B. M., Sham, P. C., Purcell, S., Banaschewski, T., Buitelaar, J., Franke, B., Sonuga-Barke, E. J. S., Ebstein, R., Eisenberg, J., Mulligan, A., Gill, M., Manor, I., Miranda, A., Mulas, F., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J. A., Steinhausen, H-C., Taylor, E. A., Thompson, M., Zhou, K., Asherson, P., & Faraone, S. V.
Population Differences in the International Multi-Centre ADHD Gene Project. Genetic Epidemiology, 32, 98-107 (2008). DOI: 10.1002/gepi.20265. (request a copy): view article

Introduction: The IMAGE sample consists of 674 families from 8 countries (Belgium, England, Germany, Holland, Ireland, Israel, Spain, & Switzerland) ascertained from clinics for combined-type attention deficit hyperactivity disorder in an offspring. 863 SNPs were successfully genotyped across 47 autosomal genes implicated in psychiatric disorders yielding an SNP density of about one SNP per 2.5 kb.

Results:
1) A global test of heterogeneity showed 269 SNPs nominally significant (expected 43). Inclusion of the Israeli population accounted for approximately 70% of these nominally significant tests.
2) Hardy-Weinberg equilibrium tests suggest that combining all these populations would induce stratification, BUT that the Northern European populations (Belgium, England, Germany, Holland, & Ireland) could be appropriate.
3) Tag SNPs were generated using pair-wise & aggressive tagging from Carlson ea [2004] & de Bakker ea [2005], respectively, in each population & applied to the other populations. Cross-population performance across Northern Europe was consistent with within population comparisons.
4) Smaller sample size for each population tended to yield more problems for the generation of aggressive tags & the application of pair-wise tags.
5) Any case-control sample employing an Israeli sample with Northern Europeans must consider stratification.
Conclusion - A Northern European tag set, however, appears to be appropriate for capturing the variation across populations.
Support: NIH.