Methods for diagnosing, preventing, and treating developmental disorders due to a combination of genetic and environmental factors
View Patent ↗The present invention discloses a novel method for identifying an individual who may be susceptible to develop a developmental disorder. In one particular example, an individual is identified who is genetically susceptible to becoming schizophrenic. In addition, the present invention discloses a novel method for identifying individuals who are genetically susceptible to have offspring with a developmental disorder. Methods of diagnosing, preventing and treating developmental disorders such as schizophrenia are also provided.
1. A method of estimating the susceptibility of an individual to have offspring that develop a developmental disorder comprising:
(a) collecting a biological sample from one or more participants; wherein a participant is either the individual or a blood relative of the individual; and wherein the biological sample contains nucleic acids and/or proteins of the participant;
(b) analyzing the nucleic acids and/or proteins from the biological sample; wherein said analyzing results in a partial or full genotype for the alleles of two or more genes involved in folate, pyridoxine, and/or cobalamin metabolism; and wherein said partial or full genotype forms a dataset of genetic explanatory variables for the participants;
(c) adding the datasets of genetic explanatory variables obtained from steps (a) and (b) to a genetic reference dataset therein forming a combined genetic dataset;
(d) formulating a model comprising the genetic explanatory variables obtained from the participants; and
(e) analyzing the combined genetic dataset by binary logistic regression;
wherein a predicted probability for the individual to have offspring that develop a developmental disorder is determined; and wherein the genetic and environmental susceptibility of an individual to have offspring that develop a developmental disorder is estimated, and wherein the individual is a pregnant woman.
2. The method of claim 1 further comprising the step of:
(f) modifying the model by adding or subtracting a genetic explanatory variable;
and re-analyzing the combined genetic dataset by binary logistic regression; wherein a model is chosen that best fits the data.
3. The method of claim 2 further comprising the step of:
(g) testing the model for goodness of fit.
4. A method of treating an asymptomatic individual determined by the method of claim 3 to be susceptible to have offspring that develop a developmental disorder comprising administering methylfolate, cobalamin or pyridoxine.
5. A method of lowering the risk of a pregnant woman who has been determined by the method of claim 3 to be susceptible to have offspring that develop a developmental disorder comprising administering methylfolate, cobalamin or pyridoxine to the pregnant woman, wherein said administering lowers the risk of the pregnant woman of giving birth to offspring with a developmental disorder.
6. A method of determining if any treatment is advisable for a pregnant woman who has been determined by the method of claim 3 to be susceptible to having offspring that develop a developmental disorder comprising determining the concentration of a risk factor from a tissue sample or body fluid from the pregnant woman; wherein when the concentration of the risk factor is statistically above or below an accepted normal range, treatment is advisable.
7. A method of monitoring the effect of the administration of methylfolate, cobalamin or pyridoxine to the pregnant woman of claim 6 , comprising determining the concentration of a risk factor from a tissue sample or body fluid from the pregnant woman; and wherein when the concentration of the risk factor is statistically within an accepted normal range, the treatment is effective.
8. The method of claim 7 wherein the risk factor is selected from the group consisting of homocysteine, folate, and cobalamin.