Pfeiffer Ruth M, Gail Mitchell H
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-7244, USA.
Genet Epidemiol. 2003 Sep;25(2):136-48. doi: 10.1002/gepi.10245.
Most previous sample size calculations for case-control studies to detect genetic associations with disease assumed that the disease gene locus is known, whereas, in fact, markers are used. We calculated sample sizes for unmatched case-control and sibling case-control studies to detect an association between a biallelic marker and a disease governed by a putative biallelic disease locus. Required sample sizes increase with increasing discrepancy between the marker and disease allele frequencies, and with less-than-maximal linkage disequilibrium between the marker and disease alleles. Qualitatively similar results were found for studies of parent offspring triads based on the transmission disequilibrium test (Abel and Müller-Myhsok, 1998, Am. J. Hum. Genet. 63:664-667; Tu and Whittemore, 1999, Am. J. Hum. Genet. 64:641-649). We also studied other factors affecting required sample size, including attributable risk for the disease allele, inheritance mechanism, disease prevalence, and for sibling case-control designs, extragenetic familial aggregation of disease and recombination. The large sample-size requirements represent a formidable challenge to studies of this type.
以往大多数用于病例对照研究以检测疾病与基因关联的样本量计算，都假定疾病基因位点是已知的，而实际上使用的是标记物。我们计算了非匹配病例对照研究和同胞病例对照研究的样本量，以检测双等位基因标记物与假定的双等位基因疾病位点所控制疾病之间的关联。所需样本量会随着标记物与疾病等位基因频率差异的增大以及标记物与疾病等位基因之间连锁不平衡程度低于最大值而增加。基于传递不平衡检验（Abel和Müller-Myhsok，1998年，《美国人类遗传学杂志》63:664 - 667；Tu和Whittemore，1999年，《美国人类遗传学杂志》64:641 - 649）对亲子三联体的研究也发现了定性相似的结果。我们还研究了影响所需样本量的其他因素，包括疾病等位基因的归因风险、遗传机制、疾病患病率，以及对于同胞病例对照设计而言，疾病的非遗传家族聚集性和重组情况。如此大的样本量需求对这类研究构成了巨大挑战。
