McMahon F J, Stine O C, Meyers D A, Simpson S G, DePaulo J R
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Univeristy School of Medicine, Baltimore, MD, USA.
Am J Hum Genet. 1995 Jun;56(6):1277-86.
The mode of inheritance of bipolar affective disorder (BPAD) appears complex, and non-Mendelian models of inheritance have been postulated. Two non-Mendelian phenomena, genomic imprinting and mitochondrial inheritance, may contribute to the complex inheritance pattern seen in BPAD. Both imprinting and mitochondrial inheritance share the feature of differential expression of the phenotype, depending on the parent of origin. In this study we tested the hypothesis of a parent-of-origin effect on the transmission of BPAD. We examined the frequency and risk of affective disorder among relatives in a sample of 31 families ascertained through treated probands with BPAD and selected for the presence of affected phenotypes in only one parental lineage. Three specific comparisons were performed: (1) the observed frequency of transmitting mothers versus transmitting fathers; (2) the observed frequency and lifetime risk of BPAD among the maternal versus the paternal relatives of probands; and (3) the observed frequency and lifetime risk of BPAD for the offspring of affected mothers compared with the offspring of affected fathers. We observed a higher than expected frequency of affected mothers (P < .04), a 2.3-2.8-fold increased risk of illness for maternal relatives (P < .006), and a 1.3- 2.5-fold increased risk of illness for the offspring of affected mothers (P < .017). In seven enlarged pedigrees, fathers repeatedly failed to transmit the affected phenotype to daughters or sons. Taken together, these findings indicate a maternal effect in the transmission of BPAD susceptibility and suggest that molecular studies of mtDNA and imprinted DNA are warranted in patients with BPAD.
双相情感障碍（BPAD）的遗传模式似乎很复杂，人们已经提出了非孟德尔遗传模型。两种非孟德尔现象，即基因组印记和线粒体遗传，可能导致了BPAD中所见的复杂遗传模式。印记和线粒体遗传都具有表型差异表达的特征，这取决于亲本来源。在本研究中，我们检验了亲本来源对BPAD传递有影响这一假设。我们在一个由31个家庭组成的样本中，研究了亲属中情感障碍的发生率和风险，这些家庭是通过接受治疗的BPAD先证者确定的，并且仅在一个亲本谱系中存在受影响的表型。进行了三项具体比较：（1）传递疾病的母亲与传递疾病的父亲的观察频率；（2）先证者的母系亲属与父系亲属中BPAD的观察频率和终生风险；（3）患病母亲的后代与患病父亲的后代中BPAD的观察频率和终生风险。我们观察到患病母亲的频率高于预期（P <.04），母系亲属的患病风险增加了2.3至2.8倍（P <.006），患病母亲的后代患病风险增加了1.3至2.5倍（P <.017）。在七个扩大的家系中，父亲多次未能将受影响的表型传递给女儿或儿子。综上所述，这些发现表明在BPAD易感性传递中存在母系效应，并提示对BPAD患者进行线粒体DNA和印记DNA的分子研究是有必要的。
