The power of linkage analysis of a disease-related endophenotype using asymmetrically ascertained sib pairs.
The power of linkage analysis of a disease-related endophenotype using asymmetrically ascertained sib pairs.
复制标题
使用不对称确定的同胞对对疾病相关内表型进行连锁分析的能力。
DOI：
10.1016/j.csda.2008.08.030
复制
发表时间：
2009
影响因子：
1.8
通讯作者：
Mendell,NancyRole
中科院分区：
文献类型：
--
作者：
Sung,Heejong;Ji,Fei;Levy,DeborahL;Matthysse,Steven;Mendell,NancyRole
A linkage study of a qualitative disease endophenotype in a sample of sib pairs, consisting of one disease affected proband and one sibling is considered. The linkage statistic compares marker allele sharing with the proband in siblings with an abnormal endophenotype to siblings with the normal endophenotype. Expressions for the distribution of this linkage statistic, in terms of the recombination fraction are derived and (1) the genetic parameter values (allele frequency and endophenotype and disease penetrance) and (2) the abnormal endophenotype rates in the population and in classes of relatives of disease affected probands. It is then shown that when either the disease or the abnormal endophenotype has additive penetrance, the expressions simplify to a monotonic function of the difference between abnormal endophenotype rates in siblings and in the population. Thought disorder is considered as a putative schizophrenia endophenotype. Forty sets of genetic parameter values that correspond to the known prevalence values for thought disorder in schizophrenic patients, siblings of schizophrenics and the general population are evaluated. For these genetic parameter values, numerical results show that the test statistic has >70% power (α=0.0001) in general with a sample of 200 or more proband-sibling pairs to detect the linkage between a marker (θ=0.01), and a locus pleiotropic for schizophrenia and thought disorder.
