Logue M W, Brzustowicz L M, Bassett A S, Chow E W C, Vieland V J
Program for Public Health Genetics, Center for Statistical Genetics Research, Iowa City, IA 52242, USA.
Hum Hered. 2006;62(1):47-54. doi: 10.1159/000096035. Epub 2006 Oct 3.
Linkage analysis using 22 Canadian pedigrees identified a promising schizophrenia candidate region on 1q23 with a maximum 2-point HLOD under a recessive model of 5.8 [Brzustowicz et al. 2000]. In the current study, we revisited this data set using a Bayesian linkage analysis technique, namely the posterior probability of linkage (PPL).
The PPL has been developed as an alternative to traditional linkage analysis. It differs from both LOD scores and 'non-parametric' methods in that it directly measures the probability of linkage given the data, and incorporates prior genomic information.
As expected, PPL results for 1q23 supported the previously observed linkage, with an estimated multipoint PPL of 99.7%. However, the PPL supported two further results: a second peak on chromosome 1 at 1p13 with a multipoint with PPL of 70% and a chromosome 17 marker (D17S784 at 17q25) with a multipoint PPL of 44%.
The PPL-based analysis presented has the advantage over other likelihood-based linkage methods in that it avoids maximization and produces a less complex view of the strength of evidence for linkage.
利用22个加拿大家系进行的连锁分析在1q23上确定了一个有前景的精神分裂症候选区域，在隐性模型下最大两点HLOD为5.8[布祖斯托维茨等人，2000年]。在本研究中，我们使用贝叶斯连锁分析技术，即连锁后验概率（PPL），重新审视了该数据集。
PPL已被开发出来作为传统连锁分析的替代方法。它与LOD评分和“非参数”方法的不同之处在于，它直接测量给定数据时的连锁概率，并纳入了先前的基因组信息。
正如预期的那样，1q23的PPL结果支持了先前观察到的连锁，估计多点PPL为99.7%。然而，PPL还支持另外两个结果：1号染色体上1p13处的第二个峰值，多点PPL为70%，以及17号染色体标记（17q25处的D17S784），多点PPL为44%。
所提出的基于PPL的分析比其他基于似然性的连锁方法具有优势，因为它避免了最大化，并对连锁证据的强度给出了不那么复杂的观点。
