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In Scientific reports ; h5-index 158.0

Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using the largest existing genomic dataset in the lithium response literature (n = 2210 across 14 international sites; 29% responders), we evaluated the degree to which lithium response could be predicted based on 47,465 genotyped single nucleotide polymorphisms using a supervised ML approach. Under appropriate cross-validation procedures, lithium response could be predicted to above-chance levels in two constituent sites (Halifax, Cohen's kappa 0.15, 95% confidence interval, CI [0.07, 0.24]; and Würzburg, kappa 0.2 [0.1, 0.3]). Variants with shared importance in these models showed over-representation of postsynaptic membrane related genes. Lithium response was not predictable in the pooled dataset (kappa 0.02 [- 0.01, 0.04]), although non-trivial performance was achieved within a restricted dataset including only those patients followed prospectively (kappa 0.09 [0.04, 0.14]). Genomic classification of lithium response remains a promising but difficult task. Classification performance could potentially be improved by further harmonization of data collection procedures.

Stone William, Nunes Abraham, Akiyama Kazufumi, Akula Nirmala, Ardau Raffaella, Aubry Jean-Michel, Backlund Lena, Bauer Michael, Bellivier Frank, Cervantes Pablo, Chen Hsi-Chung, Chillotti Caterina, Cruceanu Cristiana, Dayer Alexandre, Degenhardt Franziska, Del Zompo Maria, Forstner Andreas J, Frye Mark, Fullerton Janice M, Grigoroiu-Serbanescu Maria, Grof Paul, Hashimoto Ryota, Hou Liping, Jiménez Esther, Kato Tadafumi, Kelsoe John, Kittel-Schneider Sarah, Kuo Po-Hsiu, Kusumi Ichiro, Lavebratt Catharina, Manchia Mirko, Martinsson Lina, Mattheisen Manuel, McMahon Francis J, Millischer Vincent, Mitchell Philip B, Nöthen Markus M, O’Donovan Claire, Ozaki Norio, Pisanu Claudia, Reif Andreas, Rietschel Marcella, Rouleau Guy, Rybakowski Janusz, Schalling Martin, Schofield Peter R, Schulze Thomas G, Severino Giovanni, Squassina Alessio, Veeh Julia, Vieta Eduard, Trappenberg Thomas, Alda Martin