Author Interviews, Brigham & Women's - Harvard, Gender Differences, Genetic Research, Nature / 13.05.2020
Complement Genes May Explain Sex Differences in Lupus and Schizophrenia
MedicalResearch.com Interview with:
Nolan Kamitaki PhD
Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: Previous work from our lab found that the strongest common genetic association to schizophrenia is driven in part by copy number variation of the C4 genes. Given that lupus and Sjogren's syndrome, two autoimmune disorders, have association patterns that span the same region of the human genome, we wondered if part of the signal for these diseases may also arise from variation of C4 given that both have hypocomplementemia as a characterizing trait.
The other main finding is that these associations appear to be sex-biased, where the protection from each additional copy of the C4 gene was greater in men than in women. When we went back to the data used in the previous study from our lab association C4 variation to schizophrenia, we found that the effect was stronger in men there as well. Although the expression of C4 at the RNA level does not appear to differ between men and women, we saw that men had more C4 protein in both cerebrospinal fluid and blood plasma, suggesting that this may explain the greater genetic association in men.
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