Tiffany A. Greenwood, Ph.D.
Dr. Greenwood received her B.S. in molecular biology from UCSD and subsequently earned her Ph.D. from the Biomedical Sciences Graduate Program at UCSD in 2002 with a specialization in psychiatric genetics. She augmented her molecular genetic background with training in applied statistical genetics through her postdoctoral work with Dr. Nicholas Schork. Dr. Greenwood joined the Department of Psychiatry faculty in 2007.
Despite the clear contribution of genetics to psychiatric disorders, the mechanisms by which risk variants lead to disease are complex, and little is currently understood regarding the underlying genetic architecture and biological processes involved in illnesses. Some of the difficulty in identifying risk genes may stem from the use of diagnostic systems that group patients into discrete categories, which may have some utility for clinical care but do not adequately reflect the heterogeneous nature of psychiatric illnesses. Dr. Greenwood’s research focuses on the use of dimensional and intermediate phenotypes, as well as clinical subphenotypes, to refine the genetic signal and aid in gene discovery for psychiatric disorders, with an emphasis on bipolar disorder and schizophrenia. By integrating comprehensive clinical information with translational and genomic methods, we are better positioned to identify genetic variants and assess their impact on risk, at both the level of individual variation and through their interactions in pathways. Dr. Greenwood participates in a number of large-scale collaborations aimed at identifying genetic risk variants for psychiatric illness, including the Consortium on the Genetics of Schizophrenia (COGS), the NIMH Bipolar Genome Study (BiGS), and the Psychiatric Genomics Consortium (PGC). Dr. Greenwood’s own research in this area has been funded through a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation in 2008 for the development and utilization of a customized candidate gene array for schizophrenia and related phenotypes. She also received funding in 2010 for a K01 career development award from the National Institute of Mental Health, which is aimed at quantifying and interpreting the overlapping and unique aspects of bipolar disorder and schizophrenia.
In 2014 Dr. Greenwood received a UCSD Health Sciences Academic Senate Grant to explore bipolar disorder and schizophrenia as dimensional phenotypes that exist at the extreme of normal and beneficial population variation in positive traits related to aspects of creativity, temperament, personality, and cognitive flexibility. Recent large genome-wide studies have demonstrated a significant role of common variation in risk for both bipolar disorder and schizophrenia, 68% of which is shared between them as a common risk for psychosis. This suggests that most susceptibility alleles exist in healthy individuals and raises the intriguing possibility that the actual phenotypes being transmitted in the population may be positive traits that modulate behavior in healthy individuals, which may be maintained through balancing selection. The observation of certain positive traits or enhanced abilities in some bipolar and schizophrenia patients and particularly in their unaffected relatives further suggests a model in which large doses of risk variants cause illness but mild or moderate doses hold advantages. The advantages conferred by these positive traits, which we expect to be associated with the same genes involved in illness, may be responsible, at least in part, for the continued existence of bipolar disorder and schizophrenia in the population.
Light G*, Greenwood TA*, Swerdlow NR, Calkins ME, Freedman R, Green MF, Gur RE, Gur RC, Lazzeroni LC, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Sprock J, Stone WS, Sugar CA, Tsuang DW, Tsuang MT, Turetsky BI, Braff DL. Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study. Schizophr Bull 2014 June 5. pii: sbu064. [Epub ahead of print]. *Authors contributed equally
Cross-Disorder Group of the Psychiatric Genomics Consortium: Lee SH, Ripke S, … Greenwood TA… [375 authors], Kendler KS, Wray NR (2013) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 45:984-994
Greenwood TA, Badner JA, Byerley W, Keck PE, McElroy SL, Sadovnick AD, Remick RA, Akiskal HS, Kelsoe JR (2013) Heritability and linkage analysis of temperament in bipolar disorder. J Affective Disord 150:1031-1040. PMC3759543
Greenwood TA, Badner JA, Byerley W, Keck PE, McElroy SL, Sadovnick AD, Remick RA, Kelsoe JR (2013) Heritability and linkage analysis of personality in bipolar disorder. J Affective Disord 151:748-755. PMC3797235
Greenwood TA, Swerdlow NR, Schork NJ, Gur RE, Cadenhead KS, Calkins ME, Dobie DJ, Green MF, Lazzeroni LC, Light GA, Nuechterlein KH, Olincy A, Radant AD, Ray A, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Tsuang DW, Tsuang MT, Turetsky BI, Freedman R, Braff DL (2013) Linkage analysis of twelve endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am J psychiatry 170:521-532. PMC3878873
Greenwood TA, Bipolar Genome Study (BiGS), Kelsoe JR (2013) Genome-wide association study of irritable versus elated mania suggests genetic differences between clinical subforms of bipolar disorder. PLoS ONE 8:e53804. PMC3542199
Greenwood TA, Joo EJ, Shektman T, Sadovnick AD, Remick RA, Keck PE, McElroy SL, Kelsoe JR (2013) Association of dopamine transporter gene variants with ADHD features in bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 162B:137-145. PMC3904300
Greenwood TA, Akiskal HS, Akiskal K, Bipolar Genome Study (BiGS), Kelsoe JR (2012) Genome-wide association study of temperament as an intermediate phenotype for bipolar disorder reveals significant associations to three novel loci. Biol Psychiatry 72:303-310. PMC3925336
Greenwood TA, Light GA, Swerdlow, NR, Geyer MA, Radant AD, Braff DL (2012) Association analysis of 94 candidate genes and schizophrenia-related endophenotypes. PLoS ONE 7:e29630. PMC3258248
Psychiatric GWAS Consortium Bipolar Disorder Working Group: Sklar P, Ripke S, … Greenwood TA… [187 authors], Kelsoe JR, Purcell SM (2011) Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet 43:977-983
Greenwood TA, Beeri MS, Schmeidler J, Valerio D, Raventós H, Mora-Villalobos L, Camacho K, Carrión-Baralt JR, Angelo G, Almasy L, Sano M, Silverman JM (2011) Heritability of cognitive functions in families of successful cognitive aging probands from the Central Valley of Costa Rica. J Alzheimers Dis 27:897-907. PMC3526368
Greenwood TA, Lazzeroni, LC, Murray SS, Cadenhead KS, Calkins ME, Dobie DJ, Green MF, Gur RE, Hardiman G, Kelsoe JR, Leonard S, Light GA, Nuechterlein KH, Olincy A, Radant AD, Schork NJ, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Freedman R, Braff DL (2011) Analysis of 94 candidate genes and twelve endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia. Am J Psychiatry 168:930-946. Comment in Am J Psychiatry 168:879-881. PMC3751972
Greenwood TA, Braff DL, Cadenhead KS, Calkins ME, Dobie DJ, Freedman R, Green MF, Gur RE, Gur RC, Light GA, Mintz J, Nuechterlein KH, Olincy A, Radant AD, Seidman LJ, Siever LJ, Silverman JM, Stone WS, Swerdlow NR, Tsuang DW, Tsuang MT, Turetsky BI, Schork NJ (2007) Initial heritability analyses of endophenotypic measures for schizophrenia: The Consortium on the Genetics of Schizophrenia. Arch Gen Psychiatry 62:1242-1250