Newman Dina L, Hoffjan Sabine, Bourgain Catherine, Abney Mark, Nicolae Raluca I, Profits Elle T, Grow Michael A, Walker Karen, Steiner Lori, Parry Rodney, Reynolds Rebecca, McPeek Mary Sara, Cheng Suzanne, Ober Carole
Department of Human Genetics, University of Chicago, Chicago, IL, USA.
Eur J Hum Genet. 2004 Jul;12(7):584-90. doi: 10.1038/sj.ejhg.5201191.
Founder populations have been the subjects of complex disease studies because of their decreased genetic heterogeneity, increased linkage disequilibrium and more homogeneous environmental exposures. However, it is possible that disease alleles identified in founder populations may not contribute significantly to susceptibility in outbred populations. In this study we examine the Hutterites, a founder population of European descent, for 103 polymorphisms in 66 genes that are candidates for cardiovascular or inflammatory diseases. We compare the frequencies of alleles at these loci in the Hutterites to their frequencies in outbred European-American populations and test for associations with cardiovascular disease-associated phenotypes in the Hutterites. We show that alleles at these loci are found at similar frequencies in the Hutterites and in outbred populations. In addition, we report associations between 39 alleles or haplotypes and cardiovascular disease phenotypes (P<0.05), with five loci remaining significant after adjusting for multiple comparisons. These data indicate that this founder population is informative and offers considerable advantages for genetic studies of common complex diseases.
奠基者群体一直是复杂疾病研究的对象，因为它们的遗传异质性降低、连锁不平衡增加且环境暴露更为均质。然而，在奠基者群体中鉴定出的疾病等位基因可能对非近亲繁殖群体的易感性贡献不大。在本研究中，我们对一个欧洲裔的奠基者群体哈特派进行了研究，检测了66个可能与心血管或炎症性疾病相关的基因中的103个多态性位点。我们将哈特派这些位点的等位基因频率与其在非近亲繁殖的欧美人群中的频率进行比较，并检测它们与哈特派中心血管疾病相关表型的关联性。我们发现，这些位点的等位基因在哈特派和非近亲繁殖群体中的频率相似。此外，我们报告了39个等位基因或单倍型与心血管疾病表型之间的关联（P<0.05），在进行多重比较校正后，有5个位点仍然显著。这些数据表明，这个奠基者群体提供了丰富信息，为常见复杂疾病的遗传学研究提供了相当大的优势。
