Research in our laboratory focuses on dementia (Alzheimer’s disease & frontotemporal dementia) and addiction (alcohol dependence). In each of these projects our goal is to understand the molecular basis of disease in order to identify novel targets for therapeutic development. We use genetic and genomic approaches to identify susceptibility alleles, this work includes genome wide association studies and whole genome/exome sequencing in families multiply affected by disease and in case control cohorts. We have also pioneered the use of endophenotypes to uncover both risk and protective alleles in both our Alzheimer’s disease and our alcoholism studies. We have developed induced pluripotent stem cells from individuals with known genetic causes of disease in order to model the effects of these mutations in disease relevant cell types. Functional studies are being undertaken to understand the role of phospholipase D3 variants in Alzheimer’s Disease risk, tau mutations in frontotemporal dementia and alpha 5 nicotinic receptor variants in addiction.
Our lab focuses on transcriptional and epigenetic mechanisms by which drugs of abuse and social stress induce lasting changes in the brain to underlie addiction and depression.
Frontotemporal dementia: observational study of familial frontotemporal
Observational study of familial frontotemporal dementia caused by MAPT mutations
The goal of this project is to integrate clinical, biomarker, and neuropathological findings from subjects carrying the disease causing mutations, MAPT P301L and MAPT R406W. We wish to take advantage of the scientific opportunity presented by the recent development of tau PET imaging agents that will enable the detection of tau aggregates in the living human brain in individuals at high-risk for development of frontotemporal dementia (FTD). We hypothesize that tau aggregates will be detected at least a decade before the onset of clinical symptoms and that the spread of disease will be slower in R406W family members compared with P301L family members. By recruiting members of MAPT P301L and R406W families, we will develop a well-characterized cohort of autosomal dominantly inherited FTD, providing a resource for future clinical trials of anti-tauopathy therapies. Furthermore, by developing induced pluripotent stem cells (IPSC) from this cohort we will be able to study cellular pathologies associated with these mutations and to compare them with physiological changes in fluid and imaging biomarkers seen in human subjects. In future we plan to perform similar assessments in asymptomatic MAPT A152T risk variant carriers
Karch CM, Jeng AT, Goate AM. Extracellular Tau levels are influenced by variability in Tau that is associated with tauopathies. J Biol Chem. 2012 Dec 14;287(51):42751-62. doi: 10.1074/jbc.M112.380642. Epub 2012 Oct 26.
Addiction: Collaborative study on the genetics of alcoholism (COGA)
Collaborative Study on the Genetics of Alcoholism
The Collaborative Study on the Genetics of Alcoholism (COGA) is a tightly integrated, multifaceted and interdisciplinary project, with three overarching goals: to identify and characterize genes in which variations confer risk for (or protection from) the development of alcohol use disorders (AUDs) and related phenotypes; to understand the mechanisms by which these variants work at the molecular and cellular level; and to understand how genetic, environmental, and neurocognitive factors interact to influence the developmental trajectories of alcohol use and AUDs through an ongoing prospective study of at-risk individuals.
To accomplish these goals, COGA has assembled a team spanning a broad range of expertise, recruited a unique sample of large, ethnically diverse families densely affected by AUDs and a set of comparison families, and is carrying out a Prospective Study of adolescents and young adults from these families to elucidate how genetic risk unfolds across development against a background of documented environmental factors. We will continue our successful efforts to study a wide range of alcohol-related phenotypes, including neurophysiological endophenotypes, to maximize our power to detect novel variants/genes across the allelic spectrum. We will study the mechanism of action of newly identified genes to better understand how they affect risk and examine how the variants identified in one generation affect important precursor phenotypes and developmental trajectories during the critical adolescent/young adult phase of the next generation. At the same time, we will also explore how gender, ethnicity and environmental factors interact with these variants to moderate their effect on outcomes.
The overarching specific aims of the molecular genetics component for the next five years of COGA are:
- To identify additional genes that contribute to the risk for AUD and related phenotypes
- To explore mechanisms of action of key genes
- To examine the effects of genes and environmental factors on clinical and neurophysiological phenotypes related to the vulnerability for risky drinking, AUDs and SUDs across adolescence and young adulthood.
We have recruited 2,255 families and 17,682 individuals, many from extended families denselyaffected with AUDs. This is the largest available family resource to develop novel endophenotypes and couple them with extensive genotyping and sequencing to identify novel allelic variants across the genome.
Kapoor M, Wang JC, Wetherill L, Le N, Bertelsen S, Hinrichs AL, Budde J, Agrawal A, Almasy L, Bucholz K, Dick DM, Harari O, Xiaoling X, Hesselbrock V, Kramer J, Nurnberger JI Jr, Rice J, Schuckit M, Tischfield J, Porjesz B, Edenberg HJ, Bierut L, Foroud T, Goate A.Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families. Drug Alcohol Depend. 2014 Sep 1;142:56-62. doi: 10.1016/j.drugalcdep.2014.05.023. Epub 2014 Jun 11. PMID: 24962325
Wang JC, Foroud T, Hinrichs AL, Le NX, Bertelsen S, Budde JP, Harari O, Koller DL, Wetherill L, Agrawal A, Almasy L, Brooks AI, Bucholz K, Dick D, Hesselbrock V, Johnson EO, Kang S, Kapoor M, Kramer J, Kuperman S, Madden PA, Manz N, Martin NG, McClintick JN, Montgomery GW, Nurnberger JI Jr, Rangaswamy M, Rice J, Schuckit M, Tischfield JA, Whitfield JB, Xuei X, Porjesz B, Heath AC, Edenberg HJ, Bierut LJ, Goate AM. v A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. Mol Psychiatry. 2013 Nov;18(11):1218-24. doi: 10.1038/mp.2012.143. Epub 2012 Oct 23. PMID: 23089632
Genetic studies of Alzheimer's disease
Use of Endophenotypes in the Search for Alzheimer’s Disease (AD) Risk Genes
The goal of this study is to combine data for gene expression quantitative trait loci (eQTL), with genetic data for cerebrospinal fluid (CSF) biomarkers and case control GWAS data to identify the functional alleles that influence risk for late onset AD. Using this approach we have identified novel genes that influence levels of tau protein in the cerebrospinal fluid and risk for AD. We have demonstrated that APOE genotype influences tau levels in the CSF independently of their effects on abeta levels suggesting that APOE has pleiotropic effects on AD risk. Combining eQTL and CSF biomarker data we seeking to identify the the AD susceptibility genes within each GWAS identified locus.
Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM, Benitez BA, Jeng AT, Skorupa T, Carrell D, Bertelsen S, Bailey M, McKean D, Shulman JM, De Jager PL, Chibnik L, Bennett DA, Arnold SE, Harold D, Sims R, Gerrish A, Williams J, Van Deerlin VM, Lee VM, Shaw LM, Trojanowski JQ, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD, Peskind ER, Galasko D, Fagan AM, Holtzman DM, Morris JC; GERAD Consortium; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Genetic Consortium (ADGC), Goate AM. GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease. Neuron. 2013; 78(2):256-68. PMCID: PMC3664945; PMID: 23562540
Modifier Genes that influence age at onset or protect against development of AD
Although most cases of Alzheimer’s disease (AD) have an age at onset above age 80yrs the range in age at onset is huge with the earliest ages at onset occurring in individuals as young as the third decade of life while other individuals may live beyond one hundred years and remain cognitively normal. Even within specific risk groups, such as presenilin (PSEN) mutation carriers or apolipoportein E4 (APOE4) carriers, the range in age at onset can vary by several decades. For example individuals from an extended Colombian kindred who develop AD all carry the PSEN1E280A variant but the range in age at onset in this family has been reported to span three decades (35-62yrs. Similarly, individuals who carry an APOE4 allele may develop AD as early as 50 yrs while other individuals with this risk factor may be cognitively normal and older than 80yrs of age We hypothesize that in human populations there are both risk and protective alleles that influence the age at onset of AD. We will use GWAS data, exome chip data and whole genome/exome sequence data to identify common, low frequency and rare variants that influence age at onset of AD. Discovery analyses will focus on subjects of European ancestry but follow up analyses will also examine these variants/genes in minority populations, including family members from the PSEN1E280A Colombian kindred. Follow up of replicated genes/variants will include genetic studies to test whether these novel variants influence cerebrospinal fluid levels of beta-amlyoid or tau, implicating specific pathogenic mechanisms in AD. This project will use data generated by AD consortia including ADSP, ADGC, ADNI, CHARGE and GERAD. All data from this project will be deposited in NIAGADS and dbGAP to be used by the research community.
Benitez BA, Jin SC, Guerreiro R, Graham R, Lord J, Harold D, Sims R, Lambert JC, Gibbs JR, Bras J, Sassi C, Harari O, Bertelsen S, Lupton MK, Powell J, Bellenguez C, Brown K, Medway C, Haddick PC, van der Brug MP, Bhangale T, Ortmann W, Behrens T, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD, Haines JL, Turton J, Braae A, Barber I, Fagan AM, Holtzman DM, Morris JC; The 3C Study Group, the EADI consortium, the Alzheimer’s Disease Genetic Consortium (ADGC), Alzheimer’s Disease Neuroimaging Initiative (ADNI), the GERAD Consortium, Williams J, Kauwe JS, Amouyel P, Morgan K, Singleton A, Hardy J, Goate AM, Cruchaga C. Missense variant in TREML2 protects against Alzheimer’s disease. Neurobiol Aging 2014; 35(6):1510.e19-26. PMCID: PMC3750021; PMID: 24439484
Resources: Alzheimer’s Disease Sequencing Project
The identification of mutations causing Alzheimer’s disease in amyloid-β precursor protein, presenilin 1 and presenilin 2 led to a better understanding of the pathobiology of the condition. Read More.
Oni EN, Halikere A, Li G, Toro-Ramos AJ, Swerdel MR, Verpeut JL, Moore JC, Bello TN, Beirut LJ, Goate, A, Tischfield JA, Pang ZP, Hart RP. Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele. Sci Rep. 2016 Oct 4; 6:34341. Doi: 10.1038/srep34341. PMID: 27698409.
Lim YY, Hassenstab J, Cruchaga C, Goate A, Fagan AM, Benzinger TL, Maruff P, Snyder PJ, Masters CL, Allegri R, Chhatwal J, Farlow MR, Graff-Radford NR, Laske C, Levin J, McDade E, Ringman JM, Rossor M, Salloway S, Schofield PR, Holtzman DM, Morris JC, Bateman RJ; Dominantly Inherited Alzheimer Network. BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease. Brain 2016;139(Pt 10):2766-2777. PMID 27521573.
Olfson E, Saccone NL, Johnson EO, Chen LS, Culverhouse R, Doheny K, Foltz SM, Fox L, Gogarten SM, Hartz S, Hetrick K, Laurie CC, Marosy B, Amin N, Arnett D, Barr RG, Bartz TM, Bertelsen S, Borecki IB, Brown MR, Chasman DI, van Duijn CM, Feitosa MF, Fox ER, Franceschini N, Franco OH, Grove ML, Guo X, Hofman A, Kardia SL, Morrison AC, Musani SK, Psaty BM, Rao DC, Reiner AP, Rice K, Ridker PM, Rose LM, Schick UM, Schwander K, Uitterlinden AG, Vojinovic D, Wang JC, Ware EB, Wilson G, Yao J, Zhao W, Breslau N, Hatsukami D, Stitzel JA, Rice J, Goate A, Bierut LJ. Rare, low frequency and common coding variants in CHRNA5 and their contribution to nicotine dependence in European and African Americans. Mol Psychiatry. 2016 May;21(5)601-7. doi:10.1038/mp.2015.105. PMID: 26239294.
Kapoor M, Chou YL, Edenberg HJ, Foroud T, Martin NG, Madden PA, Wang JC, Bertelsen S, Wetherill L, Brooks A, Chan G, Hesselbrock V, Kuperman S, Medland SE, Montgomery G, Tischfield J, Whitfield JB, Bierut LJ, Heath AC, Bucholz KK, Goate AM, Agrawal A. Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures. Transl Psychiatry. 2016 Mar 22; 6:e761. doi: 10.1038/tp.2016.27. PMID: 27003187.
Jun G, Ibrahim-Verbaas C, Vronskaya M, Lambert JC, Chung J, Naj AC, Kunkle BW, Wang LS, Bis JC, Bellenguez C, Harold D, Lunetta KL, Destefano AL, Grenier-Bloey B, Sims R, Beecham GW, Smith AV, , Chouraki V< Hamilton-Nelsoin KL, Ikram MA. Fievet N, Denning N, Martin ER, Schmidt H, Kamatani Y, Dunstan ML, Valladares O, Laza AR, Zelenika D, Rairez A, Foroud TM, Choi SH, Baland A, Becker T, Kukull WA, van der Lee SJ, Pasquier F, Chruchaga C, Beekly D, Fitzpatrick AL, Hanon O, Gill M, Barber R, Gudnason V, Campion D, Love S, Bennett DA, Amin N, Berr C, Tsolaki M, Buxbaum JD, Lopez OL, Deramecourt V, Fox NC, Cantwell LB, Tarraga L, Dufouil C, Hardy J, Crane PK, Eiriksdottir G, O’Donovan MC, Montine TJ, Nalls MA, Mead S Reiman EM, Johnsson PV, Holmes C, St George-Hoslop PH, Boada M, Passmore P, Wendland JR, Schmidt R, Morgan K, Winslow AR, Powell JR, Carasquaillo M, Younkin SG, Jakobsdottir J, Kauwe JS, Wilhelmsen KC, Rujescu D, Nothern MM, Hofman A, Jones L; IGAP Consortiu, Haines JL, Psaty BM, Van Broeckhoven C, Holmans P, Launer LJ, Mayeux R, Lathrop M, Goate AM, Escott-rice V, Seshadri S, Pericak-Vance MA, Amouyel P, Williams J, van Duijn CM, Schellenberg GC, Farrer LA. A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry. 2016 Jan;21(1):108-17. Doi: 10.1038/mp.2015.23. PMID: 25778476.
Escott-Price V, Sims R, Bannister C, Harold D, Vronskaya M, Majounie E, Badarinarayan N; GERAD/PERADES; IGAP consortia, Morgan K, Passmore P, Holmes C, Powell J, Brayne C, Gill M, Mead S, Goate A, Cruchaga C, Lambert JC, van Duijn C, Maier W, Ramirez A, Holmans P, Jones L, Hardy J, Seshadri, Schellenberg GD, Amouyel P, Williams J. Common polygenic variation enhances risk prediction for Alzheimer’s disease. Brain. 2015 Dec;138(Pt 12):3673-84. doi: 10.1093/brain/awy268. PMID: 26490334.
Sadler B, Haller G, Edenberg H, Tischfield J, Brooks A, Kramer J, Schuckit M, Nurnberger J, Goate A. Positive Selection on Loci Associated with Drug and Alcohol Dependence. PLoS One. 2015 Aug 13;10(8):e0134393. doi: 10.1371/journal.pone.0134393. eCollection 2015. PMID: 26270548.
Hancock DB, Wang JC, Gaddis NC, Levy JL, Saccone NL, Stitzel JA, Goate A, Bierut LJ, Johnson EO. A multiancestry study identifies novel genetic associations with CHRNA5 methylation in human brain and risk of nicotine dependence. Hum Mol Genet. 2015 Oct 15;24(20):5940-54. doi: 10.1093/hmg/ddv303. Epub 2015 Jul 28.
Jin SC, Carrasquillo MM, Benitez BA, Skorupa T, Carrell D, Patel D, Lincoln S, Krishnan S, Kachadoorian M, Reitz C, Mayeux R, Wingo TS, Lah JJ, Levey AI, Murrell J, Hendrie H, Foroud T, Graff-Radford NR, Goate AM, Cruchaga C, Ertekin-Taner N. TREM2 is associated with increased risk for Alzheimer’s disease in African Americans. Mol Neurodegener. 2015 Apr 10;10:19. doi: 10.1186/s13024-015-0016-9. PMID: 25886450.
Jun G, Ibrahim-Verbaas CA, Vronskaya M, Lambert JC, Chung J, Naj AC, Kunkle BW, Wang LS, Bis JC, Bellenguez C, Harold D, Lunetta KL, Destefano AL, Grenier-Boley B, Sims R, Beecham GW, Smith AV, Chouraki V, Hamilton-Nelson KL, Ikram MA, Fievet N, Denning N, Martin ER, Schmidt H, Kamatani Y, Dunstan ML, Valladares O, Laza AR, Zelenika D, Ramirez A, Foroud TM, Choi SH, Boland A, Becker T, Kukull WA, van der Lee SJ, Pasquier F, Cruchaga C, Beekly D, Fitzpatrick AL, Hanon O, Gill M, Barber R, Gudnason V, Campion D, Love S, Bennett DA, Amin N, Berr C, Tsolaki M, Buxbaum JD, Lopez OL, Deramecourt V, Fox NC, Cantwell LB, Tárraga L, Dufouil C, Hardy J, Crane PK, Eiriksdottir G, Hannequin D, Clarke R, Evans D, Mosley TH Jr, Letenneur L, Brayne C, Maier W, De Jager P, Emilsson V, Dartigues JF, Hampel H, Kamboh MI, de Bruijn RF, Tzourio C, Pastor P, Larson EB, Rotter JI, O’Donovan MC, Montine TJ, Nalls MA, Mead S, Reiman EM, Jonsson PV, Holmes C, St George-Hyslop PH, Boada M, Passmore P, Wendland JR, Schmidt R, Morgan K, Winslow AR, Powell JF, Carasquillo M, Younkin SG, Jakobsdóttir J, Kauwe JS, Wilhelmsen KC, Rujescu D, Nöthen MM, Hofman A, Jones L; IGAP Consortium, Haines JL, Psaty BM, Van Broeckhoven C, Holmans P, Launer LJ, Mayeux R, Lathrop M, Goate AM, Escott-Price V, Seshadri S, Pericak-Vance MA, Amouyel P, Williams J, van Duijn CM, Schellenberg GD, Farrer LA. A novel Alzheimer disease locus located near the gene encoding tau protein. MMol Psychiatry. 2016 Jan;21(1):108-117. doi: 10.1038/mp.2015.23. Epub 2015 Mar 17. PMID: 25778476
Wetzel-Smith MK, Hunkapiller J, Bhangale TR, Srinivasan K, Maloney JA, Atwal JK, Sa SM, Yaylaoglu MB, Foreman O, Ortmann W, Rathore N, Hansen DV, Tessier-Lavigne M; Alzheimer’s Disease Genetics Consortium, Mayeux R, Pericak-Vance M, Haines J, Farrer LA, Schellenberg GD, Goate A, Behrens TW, Cruchaga C, Watts RJ, Graham RR. Nat Med. 2014 Dec;20(12):1452-7. doi: 10.1038/nm.3736. Epub 2014 Nov 24. A rare mutation in UNC5C predisposes to late-onset Alzheimer’s disease and increases neuronal cell death.
Kauwe JS, Bailey MH, Ridge PG, Perry R, Wadsworth ME, Hoyt KL, Staley LA, Karch CM, Harari O, Cruchaga C, Ainscough BJ, Bales K, Pickering EH, Bertelsen S; Alzheimer’s Disease Neuroimaging Initiative, Fagan AM, Holtzman DM, Morris JC, Goate AM. Genome-wide association study of CSF levels of 59 alzheimer’s disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation. PLoS Genet. 2014 Oct 23;10(10):e1004758. doi: 10.1371/journal.pgen.1004758. eCollection 2014 Oct.
Haller G, Kapoor M, Budde J, Xuei X, Edenberg H, Nurnberger J, Kramer J, Brooks A, Tischfield J, Almasy L, Agrawal A, Bucholz K, Rice J, Saccone N, Bierut L, Goate A. Rare missense variants in CHRNB3 and CHRNA3 are associated with risk of alcohol and cocaine dependence. Hum Mol Genet 2014; 23(3): 810-9. PMCID: PMC3888263
Kapoor M, Wang JC, Wetherill L, Le N, Bertelsen S, Hinrichs AL, Budde J, Agrawal A, Almasy L, Bucholz K, Dick DM, Harari O, Xiaoling X, Hesselbrock V, Kramer J, Nurnberger JI Jr, Rice J, Schuckit M, Tischfield J, Porjesz B, Edenberg HJ, Bierut L, Foroud T, Goate A. Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families. Drug Alcohol Dependence 2014 Jun pii: S0376-8716(14)00906-5. doi: 10.1016/j.drugalcdep.2014.05.023. PMCID: PMC4127128
Jin SC, Benitez BA, Karch CM, Cooper B, Skorupa T, Carrell D, Norton JB, Hsu S, Harari O, Cai Y, Bertelsen S, Goate AM, Cruchaga C. Coding variants in TREM2 increase risk for Alzheimer’s disease. Hum Mol Genet. 2014 Jun 4. pii: ddu277 NO PMCID yet 6/30/14
JKarch CM, Cruchaga C, Goate AM. Alzheimer’s Disease Genetics: From the Bench to the Clinic. Neuron. 2014 Jul 2;83(1):11-26. doi: 10.1016/j.neuron.2014.05.041. PMCID: PMC4120741
Karch CM, Goate AM. Alzheimer’s Disease Risk Genes and Mechanisms of Disease Pathogenesis. Biol Psychiatry 2014 May 17 pii: S0006-3223(14)00339-4. doi: 10.1016/j.biopsych.2014.05.006.
Cruchaga C, Karch CM, Jin SC, Benitez BA, Cai Y, Guerreiro R, Harari O, Norton J, Budde J, Bertelsen S, Jeng AT, Cooper B, Skorupa T, Carrell D, Levitch D, Hsu S, Choi J, Ryten M; UK Brain Expression Consortium (UKBEC), Hardy J, Ryten M, Trabzuni D, Weale ME, Ramasamy A, Smith C, Sassi C, Bras J, Gibbs JR, Hernandez DG, Lupton MK, Powell J, Forabosco P, Ridge PG, Corcoran CD, Tschanz JT, Norton MC, Munger RG, Schmutz C, Leary M, Demirci FY, Bamne MN, Wang X, Lopez OL, Ganguli M, Medway C, Turton J, Lord J, Braae A, Barber I, Brown K; The Alzheimer’s Research UK (ARUK) Consortium, Passmore P, Craig D, Johnston J, McGuinness B, Todd S, Heun R, Kölsch H, Kehoe PG, Hooper NM, Vardy ER, Mann DM, Pickering-Brown S, Brown K, Kalsheker N, Lowe J, Morgan K, David Smith A, Wilcock G, Warden D, Holmes C, Pastor P, Lorenzo-Betancor O, Brkanac Z, Scott E, Topol E, Morgan K, Rogaeva E, Singleton AB, Hardy J, Kamboh MI, St George-Hyslop P, Cairns N, Morris JC, Kauwe JS, Goate AM. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease. Nature 2014; 505(7484): 550-4. PMCID PMC:4050701
Cruchaga C, Kauwe JS, Harari O, Jin SC, Cai Y, Karch CM, Benitez BA, Jeng AT, Skorupa T, Carrell D, Bertelsen S, Bailey M, McKean D, Shulman JM, De Jager PL, Chibnik L, Bennett DA, Arnold SE, Harold D, Sims R, Gerrish A, Williams J, Van Deerlin VM, Lee VM, Shaw LM, Trojanowski JQ, Haines JL, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD, Peskind ER, Galasko D, Fagan AM, Holtzman DM, Morris JC; GERAD Consortium; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Genetic Consortium (ADGC), Goate AM. GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease. Neuron. 2013; 78(2):256-68. PMCID: PMC3664945
Kapoor M, Wang JC, Wetherill L, Le N, Bertelsen S, Hinrichs AL, Budde J, Agrawal A, Bucholz K, Dick D, Harari O, Hesselbrock V, Kramer J, Nurnberger JI Jr, Rice J, Saccone N, Schuckit M, Tischfield J, Porjesz B, Edenberg HJ, Bierut L, Foroud T, Goate A. A meta-analysis of two genome-wide association studies to identif PMCID: PMC3776011 . Hum Genet. 2013; 132(10):1141-51.
Wang JC, Spiegel N, Bertelsen S, Le N, McKenna N, Budde JP, Harari O, Kapoor M, Brooks A, Hancock D, Tischfield J, Foroud T, Bierut LJ, Steinbach JH, Edenberg HJ, Traynor BJ, Goate AM. Cis-Regulatory Variants Affect CHRNA5 mRNAExpression in Populations of African and European Ancestry. PloS One 2013; 8(11): e80204. PMCID: PMC3841173
Benitez BA, Jin SC, Guerreiro R, Graham R, Lord J, Harold D, Sims R, Lambert JC, Gibbs JR, Bras J, Sassi C, Harari O, Bertelsen S, Lupton MK, Powell J, Bellenguez C, Brown K, Medway C, Haddick PC, van der Brug MP, Bhangale T, Ortmann W, Behrens T, Mayeux R, Pericak-Vance MA, Farrer LA, Schellenberg GD, Haines JL, Turton J, Braae A, Barber I, Fagan AM, Holtzman DM, Morris JC; The 3C Study Group, the EADI consortium, the Alzheimer’s Disease Genetic Consortium (ADGC), Alzheimer’s Disease Neuroimaging Initiative (ADNI), the GERAD Consortium, Williams J, Kauwe JS, Amouyel P, Morgan K, Singleton A, Hardy J, Goate AM, Cruchaga C. Missense variant in TREML2 protects against Alzheimer’s disease. Neurobiol Aging 2013; 9(8):e1003685. PMCID: PMC3750021
Karch CM, Jeng AT, Goate AM. Extracellular tau levels are influenced by variability in tau that is associated with tauopathies. J Biol Chem. 2012; 287(51);42751-62. PMCID: PMC3522274
Meet the Team
Manav Kapoor, PhD
Assistant Professor Neuroscience, Genetics & Genomics
Kathryn Bowles, PhD
Associate Professor, Neuroscience
Jen Chyong Wang, PhD
Associate Professor Neuroscience, Genetics & Genomics
Associate Researcher I
Sarah Bertelsen, M.A., JD
Merck’s Director of Neuroscience Matthew Kennedy shares why these early results have him feeling hopeful. He is joined by Alison Goate, the director of the Ronald M. Loeb Center for Alzheimer’s Disease at Mount Sinai. Read More
As the director of the Ronald M. Loeb Center on Alzheimer’s Disease at Mount Sinai, Dr. Alison Goate specializes in researching the disease’s basic mechanisms to improve our treatment options. November is National Alzheimer’s Disease Awareness Month. Read More
Alzheimer's Association recognizes four scientists with Lifetime Achievement Awards at AAIC 2015 — July 21, 2015
The Alzheimer’s Association recognizes four leading scientists for their contributions to advancing Alzheimer’s disease and dementia research. The awards were presented during the opening session at the Alzheimer’s Association International Conference® 2015 (AAIC® 2015) in Washington, D.C. Read More
Scientists have identified early genetic markers that can potentially predict who is at an increased risk for developing Alzheimer’s, Medical Daily reported.Currently, in order to determine if someone will develop Alzheimer’s disease, doctors use tests that analyze the amount of Tau protein buildup in the central nervous system. The more Tau in an individual’s system, the more likely he or she will progress towards dementia. Read More
Postdoctoral positions are available to work on the genetics and molecular neurobiology of Alzheimer’s disease in the laboratory of Dr. Alison Goate, Director of the new Center on Alzheimer’s disease at Icahn School of Medicine at Mount Sinai, a multidisciplinary center focused on understanding the molecular mechanisms underlying genetic risk for Alzheimer’s disease and related disorders. Positions are available to work on several projects including whole genome sequencing to identify variants that protect APOE4 carriers from developing AD and whole exome sequencing in late onset AD families to identify novel genetic risk factors. Other projects use induced pluripotent stem cells and genome engineering to understand the mechanisms associated with risk or protection from AD associated with these novel genes. We have recently initiated studies on the role of PLD3 in risk for AD.
Applicants should hold a PhD in genetics, genomics, bioinformatics, computer science, statistical genetics or molecular neurobiology/stem cell biology. Please send a cover letter, curriculum vitae, and the names, phone numbers and e-mail addresses of three people who could provide letters of reference. Please submit your application materials online.