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Research at Mass General
Assistant Professor of Anaesthesia, Harvard Medical School Assistant in Genetics, Dept of Anesthesia, Critical Care and Pain Medicine Member, Center for Human Genetic Research, Massachusetts General Hospital Affiliate, Program in Medical and Population Genetics, Broad Institute
Circadian/sleep genetics and association with common diseaseGenetics of PreeclampsiaMalignant Hyperthermia gene discovery
We study the genetics of circadian rhythms, which regulate diverse physiological processes including the sleep-wake cycle, feeding behavior, hormone secretion, drug metabolism and glucose homeostasis. The lab integrates genome-wide human genetic approaches with focused mechanistic investigation to understand how genetic variation in circadian clock genes impacts normal human physiology, disease pathophysiology and response to therapy. We led genome-wide association studies of type 2 diabetes and related traits that identified over 20 risk loci for type 2 diabetes and 18 loci for glycemic traits including the circadian genes melatonin receptor (MTNR1B) and cryptochrome 2 (CRY2). Interestingly, epidemiologic and laboratory studies have demonstrated that inadequate sleep duration, sleep disorders and circadian mis-alignment such as shift work consistently increase risk of type 2 diabetes, but molecular links between these systems in humans are poorly understood. In collaboration with researchers at the Division of Sleep Medicine at the Brigham and Women’s Hospital, the lab is exploring genetic and mechanistic links between sleep/circadian dysfunction and type 2 diabetes pathogenesis.The other main focus of the lab is gene discovery in preeclampsia, a common disorder in pregnant women that strongly predicts risk of future cardiovascular disease. We investigate the maternal and fetal genetic components of disease and are engaged in identification of a) common variants through participation in international consortia, b) rare variants by sequencing of extreme and familial samples and c) genetic interaction between the maternal and fetal genomes.
In addition we have several rare disease genetics collaborations including large-scale sequencing in malignant hyperthermia.
NIH/NIDDK, Claflin Distinguished Scholar Award, William Randolph Hearst FundSociety for Obstetric Anesthesia and Perinatology
1. Saxena R*, Elbers CC*, et al. Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci. Am J Hum Genet 2012; 90(3):410-425. 2. Dupuis J*, Langenberg C*, Prokopenko I*, Saxena R*, Soranzo N* et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 2010;42:105-16.3. Prokopenko I*, Langenberg C*, Florez JC*, Saxena R*, Soranzo N* et al. Variants in the melatonin receptor 1B gene (MTNR1B) influence fasting glucose levels. Nat Genet 2009;41:77-81.4. Zeggini E*, Scott LJ*, Saxena R*, Voight B* for the Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. Meta-analysis of genome-wide association data and large-scale replication identifies several additional susceptibility loci for type 2 diabetes. Nat Genet 2008;40:638-45.5. The Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University and Novartis Institutes for BioMedical Research, Saxena R et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007;316:1331-1336.*RS led writing, study design & phenotype groups. *Equal contribution
Anesthesia, Critical Care and Pain Medicine
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