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Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identify 143 independent loci in 112 1-Mb regions, providing insights into the physiology of vitamin D and implicating genes involved in lipid and lipoprotein metabolism, dermal tissue properties, and the sulphonation and glucuronidation of 25OHD. Mendelian randomization models find no robust evidence that 25OHD concentration has causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes have (direct or indirect) causal effects on 25OHD concentration, clarifying the epidemiological relationship between 25OHD status and the health outcomes examined in this study.
Vitamin D, genetics, and the risk of schizophrenia
To explore the association between vitamin D concentrations, polygenic risk scores for schizophrenia and other brain-related outcomes in a population based sample. We will also explore the links between vitamin D and a range of brain outcomes (cognition, mental disorders). A better understanding of the etiology (both genetic and environmental) of schizophrenia will aid in improving prevention, diagnosis and treatment of this detrimental disease. Vitamin D has been shown to be a risk factor for schizophrenia, it is modifiable and can be addressed safely, simply, and cheaply via public health intervention. Low concentrations of vitamin D during early life has been shown to be associated with increased risk of schizophrenia. At the same time, schizophrenia is a highly heritable disease. We will study whether genetic factors that have been associated with increased risk of schizophrenia are also associated with low concentrations of vitamin D. We will analyze genetic risk profile scores for schizophrenia (generated from independent case-control studies) and measures of vitamin D concentration to detect the hypothesized association. We believe that the genetic risk profile score for schizophrenia includes common variants that also influence vitamin D concentration.