Causal associations between niacin bluntness and schizophrenia: a GWAS and Mendelian randomization study

Background and HypothesisNiacin 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 DesignWe 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 Results25 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). ConclusionsOur 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.