Pamela Sklar

Pamela Sklar (born July 20, 1959 in Baltimore, Maryland) is an American psychiatrist and neuroscientist. She is chief of the Division of Psychiatric Genomics and professor of psychiatry, neuroscience, and genetic and genomic sciences at the Icahn School of Medicine at Mount Sinai.^[1] Sklar is known for her large-scale gene discovery studies in bipolar disorder and schizophrenia and for making some of the first statistically meaningful gene identifications in both mental illnesses.^[2][3]

Education

Sklar completed her bachelor’s degree in classics and philosophy at St. John’s College in 1981. She went on to complete her medical degree and then her PhD in neuroscience, both at Johns Hopkins School of Medicine.

Research

Sklar’s research and clinical work focus on characterizing the biology underlying mental illnesses, in particular schizophrenia and bipolar disorder. Her studies of DNA variation have identified both common and rare genetic changes associated with these disorders.^[4][5] While working at the Broad Institute, Sklar co-founded the Stanley Center for Psychiatric Research and served as its genetics director. By studying thousands of affected individuals and comparing them with thousands of healthy people, she was the first to associate recurrent large deletions of DNA with the onset of schizophrenia and also found the first broadly reproducible genetic variants in schizophrenia as well as bipolar disorder using genome-wide association studies.^[6][7][8][9] Sklar and her colleagues discovered a molecular basis for polygenicity in schizophrenia among both rare and common DNA alterations^[10][11] and that schizophrenia and bipolar disorder are genetically linked through DNA variants that contribute to both illnesses.^[12][13] In 2011, Sklar joined the Icahn School of Medicine at Mount Sinai and became founding chief of the Division of Psychiatric Genomics there.^[14] The division’s scope includes stem cell biology, neurocognition, statistical genetics, and imaging approaches to elucidate the biological variation causing mental illness. While at Mount Sinai, Sklar published papers demonstrating that schizophrenia is linked to many ultra-rare genetic variants.^[15][16] Sklar serves as a principal investigator for the Psychiatric Genomics Consortium, the largest international collaboration in the psychiatric community.^[17] She has helped lead the consortium’s working group on bipolar disorder. She also co-founded the International Schizophrenia Consortium.

Sklar edited the textbook Neurobiology of Mental Illness,^[18] and has published more than 140 peer-reviewed scientific papers.

She was elected to the Institute of Medicine of the National Academies in 2013.^[19]

Selected publications

• Ferreira MAR, O’Donovan MC, Meng YA, Jones IR, et al. Purcell SP, Sklar P and Craddock N (2008) Collaborative genome-wide association analysis of 10,596 individuals support a role for Ankyrin-G (ANK3) and the alpha-1C subunit of the L-type voltage-gated calcium channel (CACNA1C) in bipolar disorder. Nat Genet 40:1056-8.^[9]
• International Schizophrenia Consortium, Stone JL, O'Donovan MC, Gurling H, Kirov GK, et al., Sklar P (2008) Rare chromosomal deletions and duplications increase risk of schizophrenia. Nature 455:237-41.^[6]
• International Schizophrenia Consortium. Purcell SM, Wray NR, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P (2009) Common polygenic variation contributes to risk of schizophrenia that overlaps with bipolar disorder. Nature 460:748-52.^[8]
• Psychiatric GWAS Consortium Bipolar Disorder Working Group. (2011) Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet. 43:977-83.^[7]
• Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P, Georgieva L, Rees E, Palta P, Ruderfer DM, Carrera N, Humphreys I, Johnson JS, Roussos P, Barker DD, Banks E, Milanova V, Grant SG, Hannon E, Rose SA, Chambert K, Mahajan M, Scolnick EM, Moran JL, Kirov G, Palotie A, McCarroll SA, Holmans P, Sklar P, Owen MJ, Purcell SM, O'Donovan MC. De novo mutations in schizophrenia implicate synaptic networks. Nature. 2014 506:179-84.^[20]
• Purcell SM, Moran JL, Fromer M, Ruderfer D, Solovieff N, Roussos P, O'Dushlaine C, Chambert K, Bergen SE, Kähler A, Duncan L, Stahl E, Genovese G, Fernández E, Collins MO, Komiyama NH, Choudhary JS, Magnusson PK, Banks E, Shakir K, Garimella K, Fennell T, DePristo M, Grant SG, Haggarty SJ, Gabriel S, Scolnick EM, Lander ES, Hultman CM, Sullivan PF, McCarroll SA, Sklar P. A polygenic burden of rare disruptive mutations in schizophrenia. Nature. 2014 506:185-90^[21]

References