NeuroImage: Clinical (Jan 2021)

Multisite schizophrenia classification by integrating structural magnetic resonance imaging data with polygenic risk score

  • Ke Hu,
  • Meng Wang,
  • Yong Liu,
  • Hao Yan,
  • Ming Song,
  • Jun Chen,
  • Yunchun Chen,
  • Huaning Wang,
  • Hua Guo,
  • Ping Wan,
  • Luxian Lv,
  • Yongfeng Yang,
  • Peng Li,
  • Lin Lu,
  • Jun Yan,
  • Huiling Wang,
  • Hongxing Zhang,
  • Dai Zhang,
  • Huawang Wu,
  • Yuping Ning,
  • Tianzi Jiang,
  • Bing Liu

Journal volume & issue
Vol. 32
p. 102860

Abstract

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Previous brain structural magnetic resonance imaging studies reported that patients with schizophrenia have brain structural abnormalities, which have been used to discriminate schizophrenia patients from normal controls. However, most existing studies identified schizophrenia patients at a single site, and the genetic features closely associated with highly heritable schizophrenia were not considered. In this study, we performed standardized feature extraction on brain structural magnetic resonance images and on genetic data to separate schizophrenia patients from normal controls. A total of 1010 participants, 508 schizophrenia patients and 502 normal controls, were recruited from 8 independent sites across China. Classification experiments were carried out using different machine learning methods and input features. We tested a support vector machine, logistic regression, and an ensemble learning strategy using 3 feature sets of interest: (1) imaging features: gray matter volume, (2) genetic features: polygenic risk scores, and (3) a fusion of imaging features and genetic features. The performance was assessed by leave-one-site-out cross-validation. Finally, some important brain and genetic features were identified. We found that the models with both imaging and genetic features as input performed better than models with either alone. The average accuracy of the classification models with the best performance in the cross-validation was 71.6%. The genetic feature that measured the cumulative risk of the genetic variants most associated with schizophrenia contributed the most to the classification. Our work took the first step toward considering both structural brain alterations and genome-wide genetic factors in a large-scale multisite schizophrenia classification. Our findings may provide insight into the underlying pathophysiology and risk mechanisms of schizophrenia.

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