To our best knowledge, this is the first evidence that GRN variability decreases the risk to develop BPD and schizophrenia. In addition, progranulin plasma levels are significantly decreased in patients as compared with controls. Despite both the SNPs and progranulin levels were associated with the target phenotypes, no association between such SNPs and progranulin levels were observed. This could be due to a number of reasons, including the possible regulation of translation by microRNA, the interaction of additional variants not included in this study, or the effect of medications taken at time of plasma sampling. Unfortunately, at time of DNA sampling, no matched plasma samples were taken from German controls. Therefore, these preliminary results need a further confirmation in a larger and ethnically matched population.
Progranulin and the various granulin peptides derived by elastase cleavage are implicated in a range of biological functions, including development, wound repair, inflammation and tumorigenesis 
. Whereas progranulin has anti-inflammatory properties, granulins display pro-inflammatory actions 
. Our observation that progranulin levels are low in plasma from patients with schizophrenia and BPD could imply that the balance between progranulin and granulins is altered in favour of granulins, that increase the degree of inflammation. A number of findings suggest a role for inflammatory factors in schizophrenia and BPD pathogenesis. Suvisaari et al., 
analyzed inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood, showing that mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms. In addition, Interleukin (IL)-6 serum levels were significantly increased in patients with schizophrenia as compared with controls, whereas IL-10 concentration was increased in both patients with schizophrenia and BPD 
To date, a number of Genome Wide Association Study (GWAS) have been performed in patients with either schizophrenia or BPD 
. Among these, an association with 17q21, the locus containing GRN
, has been shown in Latino populations with schizophrenia 
and in patients with BPD 
. Notably, this locus has been implicated in several other neurological and psychiatric pathologies of the central nervous system, including FTLD (see 
for review), PSP 
, and autism 
, supporting the hypothesis of common pathogenic mechanisms among these diseases. Regarding the occurrence of FTLD and schizophrenia, in support of the hypothesis that these diseases share a common aetiology, Schoder et al. 
demonstrated that the morbid risk for schizophrenia is significantly higher in relatives of FTD probands than in relatives of Alzheimer's disease probands. In three mixed families, a causal GRN
mutation was found, even in family members diagnosed with schizophrenia 
. In addition, TDP43 pathology was found in patients whose first clinical presentation was consistent with schizophrenia or BPD 
. Regarding our population, we did not have the opportunity to follow up patients and their families to ascertain the development of dementia.
In our study, the association observed in the whole population was maintained after stratifying in patients with BPD and schizophrenia, suggesting common pathogenic pathways. In line with this hypothesis, two large GWAS in BPD and schizophrenia patients, respectively, lead to the identification of the same susceptibility genes 
. Nevertheless, a replication analysis should be carried out to confirm data described here.
Regarding progranulin levels, we acknowledge that the majority of patients were treated at time of sampling, thus we can't exclude an influence of therapies on progranulin levels.
In conclusion, we demonstrated that GRN variability contributes to schizophrenia and BPD development and that progranulin plasma levels are lower in patients with BPD than in controls, although this findings need a replication in a larger cohort.