Lipid Science & Technology

Biography

Biography: Srdjan Djurovic

Abstract

Several lines of evidence suggest that genome-wide association studies (GWAS) have the potential to explain more of the ‘missing heritability’ of common complex phenotypes. However, reliable methods to identify a larger proportion of single        nucleotide        polymorphisms (SNPs) are currently lacking. Here, we present a genetic pleiotropy-informed method to improve gene discovery using GWAS summary statistics data. We apply this methodology to identify new loci associated with       schizophrenia       (SCZ), a highly heritable disorder with significant missing heritability.      Epidemiological      and clinical studies suggest co-morbidity between SCZ and     cardiovascular disease     (CVD) risk factors, including systolic blood pressure,    triglycerides   , low and hi    gh-density lipoprotein, body mass index, waist-hip-ratio, immunological parameters, and    type 2 diabetes   . We validate this ‘pleiotropic enrichment’ by demonstrating increased replication rate across independent SCZ sub-studies. We have recently replicated these findings in larger sample. The majority of  the loci are associated with both SCZ and CVD risk factors, mainly triglycerides, low and high-density   lipoproteins  . Together, these findings suggest the feasibility of using genetic pleiotropy-informed methods to impr ove gene discovery in SCZ and identify potential mechanistic relationships with various CVD risk factors. The larger part of the pleiotropic signal was found with lipid levels, suggesting that lipid biology may be involved in schizophrenia   pathophysiology  . As such, genetically determined  dyslipidemia  in schizophrenia is in line with evidence for white matter abn ormalities and myelin dysfunction and supports the neurodevelopmental hypothesis of schizophrenia.