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Lindsay A. Farrer, Ph.D.
Chief, Genetics Program
Professor, Depts. of Medicine, Neurology, and Genetics and Genomics, Boston University School of Medicine and Depts. of Epidemiology and Biostatistics, Boston University School of Public Health

Education
1985-87 NIH Postdoctoral Fellow, Dept of Human Genetics, Yale University School of Medicine
1985 Ph.D., Indiana University School of Medicine (Medical Genetics)
1981 B.A., University of North Carolina (Population Genetics)

Other Appointments
Director, Genetic Epidemiology Center, Boston University School of Medicine
Genetic Epidemiologist, ENRVA Hospital, Bedford, Massachusetts
Research Interests

In collaboration with other laboratories worldwide, Dr. Farrer has localized genes causing a variety of rare and common disorders including Alzheimer disease (AD), Wilson disease, Machado-Joseph disease, Waardenburg syndrome, hypertension, sensorineural deafness, and osteoarthritis. Dr. Farrer's team is developing genetic mapping methods for locating genetic modifiers for disorders whose primary defects are already known, but account for only a small portion of the phenotypic variation. Such modifier genes will probably be more amenable than the primary structural genes to strategies for delaying or modulating expression. Under Dr. Farrer's leadership, the MIRAGE Project, a multi center study of AD funded since 1991 by the National Institute on Aging, has made several important contributions to our understanding of the interactions between genetic and environmental factors for the disorder. This study has a particular emphasis on the genetics of AD in African Americans. Dr. Farrer and his colleagues in the Genetics Program have an integral role developing new multi disciplinary research programs. They are working with other BUSM researchers on the Hypertension SCOR Program which is dedicated to identifying genes for hypertension and blood pressure regulation disorders; on the Atherosclerosis SCOR Program, part of which is focused on genetic modulators of endothelial dysfunction; the genetics of severe asthma; with the Hematology/Oncology section on projects aimed at identifying genes influencing severity and expression of sickle cell anemia; and the New England Centenarian Study on the genetic basis of exceptional longevity. In collaboration with researchers at several other institutions, Dr. Farrer is conducting a genome scan to search for genes conveying susceptibility to cocaine and opioid dependence. His laboratory is also coordinating an extremely large international study to identify genes for metabolic syndrome, a common disorder characterized by atherosclerosis, insulin resistance, hypertension and central obesity.

Dr. Farrer is a graduate of the University of North Carolina in Chapel Hill, received his Ph.D. from the Indiana University School of Medicine and gained additional training in genetic epidemiology at Yale University.

Selected Publications

Erlich PM, Lunetta KL, Cupples LA, Huyck M, Green RC, Baldwin CT, Farrer LA.  Polymorphisms in the PON gene cluster are associated with Alzheimer disease.  Hum Mol Genet 2006; 15:77-85.

Gelernter J, Panhuysen C, Wilcox M, Hesselbrock V, Rounsaville B, Poling J, Weiss R, Sonne S, Farrer LA, Kranzler HR.  Genomewide linkage scan for opioid dependence and related traits.  Am J Hum Genet  2006;78:759-769.

Meng Y, Baldwin CT, Bowirrat A, Waraska K, Inzelberg R, Friedland RP, Farrer LA.  Association of polymorphisms in the angiotensin-converting enzyme gene and Alzheimer disease in an Israeli-Arab community.  Am J Hum Genet  2006; 78:871-877.

Nolan VG, Adewoye A, Baldwin CT, Wang L, Ma Q, Wyszynski DF, Farrell JJ, Sebastiani P, Farrer LA, Steinberg MH.  Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-ß/BMP pathway.  Br J Hematol 2006;133:570-578.

Yu Y, Panhuysen C, Kranzler HR, Hesselbrock V, Rounsaville B, Poling J, Wilcox M, Weiss R, Brady K, Farrer LA, Gelernter J.  Intronic variants in the dopa decarboxylase (DDC) gene are associated with smoking behavior in European-Americans and African-Americans.  Hum Mol Genet 2006;15:2192-2199.

Gelernter J, Panhuysen C, Weiss R, Brady K, Hesselbrock V, Rounsaville B, Poling J, Wilcox M, Farrer LA , Kranzler HR.  Genomewide linkage scan for cocaine dependence and related traits: Significant linkages for a cocaine-related trait and for cocaine-induced paranoia.  Am J Med Genet 2005; 136:45-52.

Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C, Farrer LA .  Complement factor H polymorphism and age-related macular degeneration.  Science 2005; 308:421-424.

Yu Y, Wyszynski DF, Waterworth DM, Wilton SD, Barter PJ, Kesäniemi YA,, Mahley RW, McPherson R, Waeber G, Bersot TP, Ma Q, Sharma SS, Middleton LT, Sundseth SS, Mooser V, Grundy SM, Farrer LA .  Multiple QTLs influencing triglyceride and HDL cholesterol levels identified in families with atherogenic dyslipidemia.  J Lip Research 2005; 46:2202-2213.

Yip AG, McKee AC, Green RC, Wells J, Young H, Cupples LA, Farrer LA .  APOE, vascular pathology and the AD brain.  Neurology 2005; 65:259-265.

Saleh M, Vaillancourt JP, Graham RK, Huyck M, Srinivasula SM, Alnmeri ES, Steinberg MH, Nolan V, Baldwin CT, Hotchkiss RS, Buchman TG, Zehnbauer BA, Hayden MR, Farrer LA, Roy S, Nicholoson DW. Differential modulation of endotoxin responsiveness by human caspase-12 polymorphs. Nature. 2004 May 6;429(6987):75-9.

Wyszynski DF, Baldwin CT, Cleves MA, Amirault Y, Nolan VG, Farrell JJ, Bisbee A, Kutlar A, Farrer LA, Steinberg MH. Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. Cell Mol Biol (Noisy-le-grand). 2004 Feb;50(1):23-33.

Roberts JS, Barber M, Brown TM, Cupples LA, Farrer LA, LaRusse SA, Post SG, Quaid KA, Ravdin LD, Relkin NR, Sadovnick AD, Whitehouse PJ, Woodard JL, Green RC. Who seeks genetic susceptibility testing for Alzheimer's disease? Findings from a multisite, randomized clinical trial. Genet Med. 2004 Jul-Aug;6(4):197-203.

Farrer LA, Bowirrat A, Friedland RP, Waraska K, Korczyn AD, Baldwin CT. Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab Community. Hum Molec Genet 2003; 12; 415-422.

Graff-Radford N, Green RC, Go RCPG, Hutton ML, Edeki T, Bachman D, Adamson JL, Griffith P, Willis FB, Williams M, Hipps Y, Haines JL, Cupples LA, Farrer LA. Association between APOE genotype and Alzheimer disease in African Americans. Arch Neurol 2002; 59:594-600.

Green RC, Cupples LA, Go RCPG, Benke KS, Edeki T, Griffith PA, Wiliiams M, Hipps Y, Graff-Radford N, Bachman D, Farrer LA, for the MIRAGE Study Group. Risk of dementia among white and African American relatives of patients with Alzheimer's disease. JAMA 2002; 287:329-336.

Farrer LA. Intercontinental epidemiology of Alzheimer disease: global approach to gene hunting. JAMA 2001; 285:796-798.

St. George-Hyslop PH, Farrer LA, Goedert M. Alzheimer disease and the fronto-temporal dementias: diseases with cerebral deposition of fibrillar proteins. In Molecular and Metabolic Basis of Inherited Disease, 8th edition. 2000, McGraw-Hill, Inc., volume 4, chapter 234, pages 5785-5899.

Guo Z, Cupples LA, Kurz A, Auerbach SH, Volicer L, Chui H, Green RC, Sadovnick AD, Duara R, DeCarli C, Johnson K, Go RC, Growdon JH, Kukull WA, Farrer LA. Head injury and the risk of Alzheimer disease in the MIRAGE Study. Neurology 2000; 54:1316-1323.

Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song Y-Q, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang D-S, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LA, Sorbi S, Bruni A, Fraser P, St. George-Hyslop P. A novel protein (nicastrin) modulates presenilin-mediated notch/glp-1 and betaAPP processing. Nature 2000; 407: 48-54.

Baima J, Nicolaou M, Schwartz F, DeStefano AL, Manolis A, Gavras I, Farrer LA, Baldwin C, Gavras H. Evidence for linkage between essential hypertension and a putative locus on human chromosome 17. Hypertension 1999; 34:4-7.

Rogaeva EA, PremkumarS, Grubber J, Serneels L, Scott W, Kawarai T, Yu G, Hill D, Aboudonia S, Martin E, Claxton C, Song Y, Roberge B, Saunders A, Roses AD, Schmechel D, Crane A, Small G, Conneally PM, Haines JL, Van Leuven F, St. George-Hyslop P, Farrer LA, Pericak-Vance MA. An alpha-2-macroglobulin insertion-deletion polymorphism in Alzheimer disease. Nature Genetics 1999; 22:19-22.

Farrer LA. Locating genetic modifiers for inherited neurodegenerative diseases. In Peters A, Morrison JH, (eds). Cerebral Cortex, volume 14. Neurodegenerative and Age-Related Changes in Structure and Function of the Cerebral Cortex. New York: Plenum Publishing Co., 1999; Chapter 12, pp. 433-459.

Farrer LA, Cupples LA. Determining the genetic component of a disease. In: Haines JL, Pericak-Vance MA (eds). Approaches to Gene Mapping Studies in Complex Human Diseases. New York, John Wiley & Sons, 1998; Chapter 5, pp. 93-130.

DeStefano AL, Baldwin CT, Burzstyn M, Gavras I, Handy DE, Joost O, Martel T, Nicolaou M, Schwartz F, Streeten DHP, Farrer LA, Gavras H. Autosomal dominant orthostatic hypotensive disorder maps to chromosome 18q. Am J Hum Genet 1998; 63:1425-1430.

Rogaeva E, Premkumar S, Song Y, Sorbi S, Brindle N, Psyche MRC, Paterson A, Duara R, Levesque G, Yu G, Nishimura M, Ikeda M, O’Tooke C, Kawarai T, Jorge R, Vilarino D, Bruni AC, Farrer LA, St. George-Hyslop PH. Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA. 1998; 280:614-618.

DeStefano AL, Cupples LA, Arnos KS, Asher JH, Baldwin CT, Carey M, da Silva EO, Friedman TB, Greenberg J, Landa B, Milunsky A, Morell R, Nance WE, Pandya A, Ramesar R, Read A, Tassebejhi M, Wilcox ER, Farrer LA. Correlation between Waardenburg syndrome phenotype and genotype in a population of individuals with identified PAX3 mutations. Hum Genet 1998; 102:499-506.

Kalinsky H, Funes A, Maron H, Zeldin A, Pel-Or Y, Korostishevsky M, Gershoni-Baruch R, Farrer LA, Bonné-Tamir B. Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups. Human Mutat. 1998; 11:145-151.

Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 1997; 278: 1349-1356.

Rao VS, Cupples LA, van Duijn CM, Kurz A, Green RC, Chui H, Duara R, Auerbach SA, Volicer L, Wells J, van Broeckhoven C, Growdon JH, Haines JL, Farrer LA. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4. Am J Hum Genet 1996; 59:664-675.
Farrer LA. Genetics and the dementia patient. Neurologist. 1997; 3:13-30.

DeStefano AL, Cupples LA, Maciel P, Gaspar C, Radvany J, Dawson DM, Sudarsky L, Corwin L, Coutinho P, MacLeod P, Sequeiros J, Rouleau G, Farrer LA. Familial factor independent of CAG repeat length influences age at onset of Machado-Joseph disease. Am J Hum Genet 1996; 59:119-127.

Lautenschlager NT, Cupples LA, Rao VS, Auerbach SA, Becker R, Burke J, Chui H, Duara R, Foley EJ, Glatt S, Green RC, Jones R, Karlinsky H, Kukull W, Kurz A, Larson EB, Martelli K, Sadovnick AD, Smith GE, Volicer L, Waring SC, Growdon JH, Farrer LA. Risk of dementia among relatives of Alzheimer disease patients in the MIRAGE study: What is in store for The "Oldest Old"? Neurology 1996; 46:641-650.

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