Klein Nadja, Entwistle Andrew, Rosenberger Albert, Kneib Thomas, Bickeböller Heike
Humboldt University of Berlin, Berlin, Germany.
University Medical Centre Göttingen, Göttingen, Germany.
J Appl Stat. 2019 Dec 19;47(11):2066-2080. doi: 10.1080/02664763.2019.1704226. eCollection 2020.
In this paper, we propose the class of generalized additive models for location, scale and shape in a test for the association of genetic markers with non-normally distributed phenotypes comprising a spike at zero. The resulting statistical test is a generalization of the quantitative transmission disequilibrium test with mating type indicator, which was originally designed for normally distributed quantitative traits and parent-offspring data. As a motivational example, we consider coronary artery calcification (CAC), which can accurately be identified by electron beam tomography. In the investigated regions, individuals will have a continuous measure of the extent of calcium found or they will be calcium-free. Hence, the resulting distribution is a mixed discrete-continuous distribution with spike at zero. We carry out parent-offspring simulations motivated by such CAC measurement values in a screening population to study statistical properties of the proposed test for genetic association. Furthermore, we apply the approach to data of the Genetic Analysis Workshop 16 that are based on real genotype and family data of the Framingham Heart Study, and test the association of selected genetic markers with simulated coronary artery calcification.
在本文中，我们针对包含零处尖峰的非正态分布表型，提出了用于位置、尺度和形状的广义相加模型类，以检验遗传标记与这类表型的关联性。由此产生的统计检验是对带有交配型指标的定量传递不平衡检验的推广，该检验最初是为正态分布的数量性状和亲子数据设计的。作为一个启发性例子，我们考虑冠状动脉钙化（CAC），它可通过电子束断层扫描准确识别。在研究区域，个体要么对所发现的钙含量有连续测量值，要么体内无钙。因此，所得分布是一种在零处有尖峰的混合离散 - 连续分布。我们在一个筛查人群中，基于此类CAC测量值进行亲子模拟，以研究所提出的基因关联检验的统计特性。此外，我们将该方法应用于遗传分析研讨会16的数据，这些数据基于弗雷明汉心脏研究的真实基因型和家系数据，并检验所选遗传标记与模拟冠状动脉钙化的关联性。
