Causal associations between niacin bluntness and schizophrenia: a GWAS and Mendelian randomization study
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background and Hypothesis
Niacin skin bluntness is a promising biomarker for schizophrenia, especially in precision medicine, as it helps identify a distinct subgroup (around 1/3) of patients with schizophrenia who experience severe functional impairment. However, research has not clarified if this phenotype is just a byproduct of the onset of the disease or is involved in the etiology of schizophrenia. We hypothesize that niacin bluntness reflects causal alterations in schizophrenia.
Study Design
We firstly conducted a quasi-genome-wide association analysis within schizophrenia patients to identify instrumental SNPs for niacin response. Then a two-sample bi-directional Mendelian randomization (MR) analysis was implemented to estimate the potential causal effects between niacin response and schizophrenia.
Study Results
25 independent SNPs showed a trend of genome-wide significant association (p<E-05) with niacin response in schizophrenia. In the MR analysis, the F statistics of the two instrumental SNPs for niacin response is 30.77, indicating a proper strength. As heterogeneity of the SNPs was detected (p<0.05), the result of inverse variance weighted method for multiplicative random effects was adopted for evaluation of the detected causal effect (OR=1.272, p=9.46E-03). In reverse MR analysis, none of the methods supported a causal effect of schizophrenia on niacin response (all p>0.05).
Conclusions
Our results revealed that the attenuated niacin response caused schizophrenia but not vice versa. Etiological studies on niacin bluntness in schizophrenia are needed and will pave the way for biomarker-guided personalized treatment in future.
