Copy number variation profile-based genomic typing of premenstrual dysphoric disorder in Chinese.

Premenstrual dysphoric disorder (PMDD) affects nearly 5% women of reproductive age. Symptomatic heterogeneity, together with largely unknown genetics, have greatly hindered its effective treatment. In the present study, analysis of genomic sequencing-based copy-number-variations (CNVs) called from 100-kb white blood cell DNA sequence windows by means of semi-supervised clustering led to the segregation of patient genomes into the D and V groups, which correlated with the depression and invasion clinical types respectively with 89.0% consistency. Application of diagnostic CNV features selected using the correlation-based machine-learning method enabled the classification of the CNVs obtained into the D group, V group, total-patient group and control group with an average accuracy of 83.0%. The power of the diagnostic CNV features was 0.98 on average, suggesting that these CNV features could be employed for the molecular diagnosis of the major clinical types of PMDD. This demonstrated concordnce between the CNV profiles and clinical types of PMDD supported the validity of symptom-based diagnosis of PMDD for differentiating between its two major clinical types, as well as the predominanly genetic nature of PMDD with a host of overlaps between multiple susceptibility genes/pathways and the diagnostic CNV features as indicators of involvement in PMDD etiology.