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  • Konte, B, et al. (author)
  • HLA-DQB1 6672G>C (rs113332494) is associated with clozapine-induced neutropenia and agranulocytosis in individuals of European ancestry
  • 2021
  • In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1, s. 214-
  • Journal article (peer-reviewed)abstract
    • The atypical antipsychotic clozapine is the only effective medication for treatment-resistant schizophrenia. However, it can also induce serious adverse drug reactions, including agranulocytosis and neutropenia. The mechanism by which it does so is largely unknown, but there is evidence for contributing genetic factors. Several studies identified HLA-DQB1 variants and especially a polymorphism located in HLA-DQB1 (6672G>C, rs113332494) as associated with clozapine-induced agranulocytosis and neutropenia. We analysed the risk allele distribution of SNP rs113332494 in a sample of 1396 controls and 178 neutropenia cases of which 60 developed agranulocytosis. Absolute neutrophil counts of 500/mm3 and 1500/mm3 were used for defining agranulocytosis and neutropenia cases, respectively. We also performed association analyses and analysed local ancestry patterns in individuals of European ancestry, seeking replication and extension of earlier findings. HLA-DQB1 (6672G>C, rs113332494) was associated with neutropenia (OR = 6.20, P = 2.20E−06) and agranulocytosis (OR = 10.49, P = 1.83E−06) in individuals of European ancestry. The association signal strengthened after including local ancestry estimates (neutropenia: OR = 10.38, P = 6.05E−08; agranulocytosis: OR = 16.31, P = 1.39E−06), with effect sizes being considerably larger for agranulocytosis. Using local ancestry estimates for prediction, the sensitivity of rs113332494 increased from 11.28 to 55.64% for neutropenia and from 16.67 to 53.70% for agranulocytosis. Our study further strengthens the evidence implicating HLA-DQB1 in agranulocytosis and neutropenia, suggesting components of the immune system as contributing to this serious adverse drug reaction. Using local ancestry estimates might help in identifying risk variants and improve prediction of haematological adverse effects.
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  • Van Der Weide, R.Y., et al. (author)
  • Innovation in mechanical weed control in crop rows
  • 2008
  • In: Weed research (Print). - : Wiley. - 0043-1737 .- 1365-3180. ; 48:3, s. 215-224
  • Journal article (peer-reviewed)abstract
    • Weed control within crop rows is one of the main problems in organic farming. For centuries, different weed removal tools have been used to reduce weeds in the crop rows. Stimulated by the demand from organic farmers, research in several European countries over the last decade has focused on mechanisation using harrowing, torsion finger weeding and weeding with compressed air (Pneumat). Intelligent weeders are now being developed which offer more advanced ways to control weeds, including larger ones and to leave the crop plants unharmed. One of the first commercially available intelligent weeders, the Sarl Radis from France, has a simple crop detection system based on light interception, which guides a hoe in and out of the crop row, around the crop plants. The inclusion of innovative technologies, including advanced sensing and robotics, in combination with new cropping systems, might lead to a breakthrough in physical weed control in row crops leading to significant reductions, or even elimination, of the need for hand weeding. © 2008 The Authors.
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