Combined haplotype relative risk (CHRR): a general and simple genetic association test that combines trios and unrelated case-controls.

@article{citeulike:3041762, abstract = {In some genetic association studies, samples contain both parental and unrelated controls. Under such scenarios, instead of analyzing only trios using family-based association tests or only unrelated subjects using a case-control study design, Nagelkerke et al. ([2004] Eur. J. Hum. Genet. 12:964-970) and Epstein et al. ([2005] Am. J. Hum. Genet. 76:592-608) proposed methods that implemented a likelihood ratio test to combine the two different types of data. In this article, we put forward a more powerful and simplified strategy to combine trios with unrelated subjects based on the haplotype relative risk (HRR) (Falk and Rubinstein [1987] Ann. Hum. Genet. 51:227-233). The HRR compares parental marker alleles transmitted to an affected offspring to those not transmitted as a test for association, a strategy that is similar to a case-control study that compares allele frequencies in diseased cases to those of unrelated controls. We prove that affected offspring can be pooled with diseased cases and that parental controls can be treated as unrelated controls when the trios and unrelated subjects are randomly sampled from the same population. Therefore, unrelated subjects can be incorporated into the HRR intuitively and effortlessly. For trios without complete parental genotypes, we adopted the strategy proposed by (Guo et al. [2005a] BMC Genet. 6:S90; [2005b] Hum. Hered. 59: 125-135), which is more feasible than the one proposed by Weinberg ([1999] Am. J. Hum. Genet. 64:1186-1193). In addition, simulation results suggest that the combined haplotype relative risk is more powerful than Epstein et al.'s method regardless of the disease prevalence in a homogeneous population. Genet. Epidemiol. 2008. (c) 2008 Wiley-Liss, Inc.}, address = {Clinical Research Program, Children's Hospital Boston, Boston, Massachusetts.}, author = {Guo, Chao-Yu Y. and Lunetta, Kathryn L L. and Destefano, Anita L L. and Cupples, L Adrienne A. }, citeulike-article-id = {3041762}, doi = {http://dx.doi.org/10.1002/gepi.20356}, issn = {1098-2272}, journal = {Genetic epidemiology}, keywords = {family, haplotype, sibpair, software, trio, unrelated}, month = {July}, posted-at = {2008-07-25 06:26:41}, priority = {2}, title = {Combined haplotype relative risk (CHRR): a general and simple genetic association test that combines trios and unrelated case-controls.}, url = {http://dx.doi.org/10.1002/gepi.20356}, year = {2008} }

TY - JOUR ID - citeulike:3041762 L3 - citeulike-article-id:3041762 TI - Combined haplotype relative risk (CHRR): a general and simple genetic association test that combines trios and unrelated case-controls. JF - Genetic epidemiology AD - Clinical Research Program, Children's Hospital Boston, Boston, Massachusetts. SN - 1098-2272 N2 - In some genetic association studies, samples contain both parental and unrelated controls. Under such scenarios, instead of analyzing only trios using family-based association tests or only unrelated subjects using a case-control study design, Nagelkerke et al. ([2004] Eur. J. Hum. Genet. 12:964-970) and Epstein et al. ([2005] Am. J. Hum. Genet. 76:592-608) proposed methods that implemented a likelihood ratio test to combine the two different types of data. In this article, we put forward a more powerful and simplified strategy to combine trios with unrelated subjects based on the haplotype relative risk (HRR) (Falk and Rubinstein [1987] Ann. Hum. Genet. 51:227-233). The HRR compares parental marker alleles transmitted to an affected offspring to those not transmitted as a test for association, a strategy that is similar to a case-control study that compares allele frequencies in diseased cases to those of unrelated controls. We prove that affected offspring can be pooled with diseased cases and that parental controls can be treated as unrelated controls when the trios and unrelated subjects are randomly sampled from the same population. Therefore, unrelated subjects can be incorporated into the HRR intuitively and effortlessly. For trios without complete parental genotypes, we adopted the strategy proposed by (Guo et al. [2005a] BMC Genet. 6:S90; [2005b] Hum. Hered. 59: 125-135), which is more feasible than the one proposed by Weinberg ([1999] Am. J. Hum. Genet. 64:1186-1193). In addition, simulation results suggest that the combined haplotype relative risk is more powerful than Epstein et al.'s method regardless of the disease prevalence in a homogeneous population. Genet. Epidemiol. 2008. (c) 2008 Wiley-Liss, Inc. KW - family KW - haplotype KW - sibpair KW - software KW - trio KW - unrelated AU - Guo, Chao-Yu AU - Lunetta, Kathryn L AU - Destefano, Anita L AU - Cupples, L Adrienne PY - 2008/07/17/ UR - http://dx.doi.org/10.1002/gepi.20356 ER -