Malhotra Alka, Cromer Kevin, Leppert Mark F, Hasstedt Sandra J
Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
Diabetes and Obesity Research Unit, Genetic Basis of Human Disease, Translational Genomics Research Institute, 445 N Fifth Street, Phoenix, AZ, 85004, USA.
J Hum Genet. 2005;50(2):69-75. doi: 10.1007/s10038-004-0222-8. Epub 2005 Jan 29.
Quantitative trait phenotypes and linked marker genotypes were simulated for a range of models with different sets of assumptions based on displacement, prevalence, and heritability of the trait in 30 Utah Centre d'Etude du Polymorphisme Humain (CEPH) families. The gain in power by the addition of 15 families was also estimated by extrapolation. Power was evaluated using both parametric single locus (PSL) models and variance components (VC) methods for two situations: (1) a single marker with 75% heterozygosity and a recombination fraction of 0.05, and (2) a fully informative marker as an approximation to multipoint analysis. When the simulation and analysis models were both dominant with the same prevalence, power > or =80% for lod >3 was estimated when quantitative trait locus variance was > or =40% with a displacement of 2.5 or 3. Power was 5-15% lower for recessive models compared to dominant models. With the addition of 15 families, an average increase in power of 17% and 22% was estimated for the dominant and recessive models, respectively. In PSL analyses, power was estimated at < or =20% when the dominance was misspecified. This investigation delineates parameter conditions under which this unique sample affords adequate power to detect linkage using both PSL and VC methods.
基于犹他州30个人类多态性研究中心(CEPH)家庭中某一性状的移位、患病率和遗传力,针对一系列具有不同假设集的模型模拟了数量性状表型和连锁标记基因型。还通过外推法估计了增加15个家庭后检验效能的提高情况。在两种情况下,使用参数单基因座(PSL)模型和方差成分(VC)方法评估检验效能:(1)一个杂合度为75%、重组率为0.05的单个标记,以及(2)一个完全信息性标记作为多点分析的近似。当模拟模型和分析模型均为显性且患病率相同时,当数量性状基因座方差≥40%且移位为2.5或3时,估计对数优势比分(lod)>3时检验效能≥80%。与显性模型相比,隐性模型的检验效能低5 - 15%。增加15个家庭后,估计显性模型和隐性模型的检验效能平均分别提高17%和22%。在PSL分析中,当显性指定错误时,检验效能估计≤20%。本研究描述了在此独特样本中使用PSL和VC方法检测连锁时具有足够检验效能的参数条件。