Carlos Cruchaga, Ph.D.

Associate Professor

Human and Statistical Genetics Program
Neurosciences Program

  • 314-286-0546

  • 314-362-2244

  • 8134

  • BJC Institute of Health (9th floor). 425 S Euclid Ave.

  • CCruchaga@WUSTL.EDU


  • Alzheimer’s disease, Parkinson disease, Next-generation sequencing, complex disease, computational biology, gene expression, genetics

  • We are using the next-generation sequencing technology to identify novel genetic variants implicated in neurodegeneration

Research Abstract:

My research interests are focused on the in the identification of genetic variants implicated in Alzheimer’s disease (AD). The identification of such factors will help to a better understanding of the pathobiology of the disease and to the identification of new therapeutic targets. The cumulative impact of rare variants on common diseases is currently unknown, but recent studies have implicated rare genetic variants in many complex diseases. Consequently, it has been suggested that the combined effect of rare deleterious mutations could explain a substantial fraction of genetic susceptibility to many common diseases. Genome-wide association studies (GWAS) can interrogate the association of up to 1 million common single nucleotide polymorphisms (SNPs) with risk for disease or other phenotypes. However, the GWAS approach can only identify common variation; it is not designed to detect multiple rare variants in the same gene. Only by resequencing candidate genes in a large population these variants can be identified. In the lab we are using the second-generation sequencing technology to identify rare variants implicated in Alzheimer’s and Parkinson’s disease. We are using both, targeted and whole-exome sequencing to identify novel pathogenic variants and sequences variants that influence age at onset and disease progression.

Selected Publications:

Jin SC, Benitez BA, Karch CM, Cooper B, Skorupa T, Carrell D, Norton J, Hsu S, Harari O, Cai Y, Bertelsen S, Goate AM and Cruchaga C. Coding variants in TREM2 increase risk for Alzheimer’s disease. Human Mol. Genet. 2014 Jun 4. pii: ddu277. PMID: 24899047

Cruchaga C, Ebbert MT, Kauwe JS. Genetic discoveries in AD using CSF amyloid and tau. Curr Genet Med Rep. 2014 Mar 1;2(1):23-29. PMID: 24729949. PMC3979575

Deming Y, Cruchaga C. TMEM106B: a strong FTLD disease modifier. Acta Neuropathol. 2014 Feb 1. PMID: 24488309

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 Dec 21. pii: S0197-4580(13)00649-0. doi: 10.1016/j.neurobiolaging.2013.12.010. [Epub ahead of print] PMID: 24439484. PMC3961557

Cruchaga C*, Karch CM, Jin SC, Harari O, , Cai Y , Benitez B, Jeng AT, Skorupa T, Carrell D, Bertelsen S, Bailey M, McKean D, Shulman JM, De Jager PL, Chibnik L, Bennett DA, Fagan AN, Holtzman DM, Morris JC, Kauwe JSK, and Goate AM. Rare coding variants in Phospholipase D3 (PLD3) confer risk for Alzheimer’s disease. Nature. 2014 Jan 23;505(7484):550-4. doi: 10.1038/nature12825. Epub 2013 Dec 11.PMID: 24336208. PMC4050701 (*Corresponding author)

Benitez BA, and Cruchaga C. TREM2 p.R47H variant increases risk for Parkinson’s Disease. N Engl J Med.. 2013;369(16):1564-70. PMID: 24131187. PMCID:

Benitez BA, Karch CM, Cai Y, Jin SC, Cooper B, Carrell D, Bertelsen S, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Genetic and Environmental Risk for Alzheimer`s Disease Consortium (GERAD), Hotlzman D, Morris JC, Goate AM, Cruchaga C. The PSEN1, p.E318G Variant Increases the Risk of Alzheimer`s Disease in APOE-ε4 Carriers. PLoS Genetics. 10.1371/journal.pgen.1003685. PMID: 23990795. PMCID: PMC3750021

Harms M, Benitez B, Cairns N, Cooper B, Cooper P, Mayo K, Carrell D, Faber K, Williamson J, Bird T, Diaz-Arrastia R, Foroud T.M, Boeve B.F, Graff-Radford N.R, Mayeux R, Chakraverty S, Goate AM., and Cruchaga C, for the NIA-LOAD/NCRAD Family Study Consortium. C9ORF72 hexanucleotide repeat expansions in clinical Alzheimer’s disease. JAMA Neurol. 2013 Apr 15:1-6. PMID: 23588422. PMCID: PMC3681841

Cruchaga C, Kauwe JSK, Harari O, Jin SC, Cai Y, Karch CM, Benitez B, Jeng AT, Skorupa T, Carrell D, Bertelsen S, Bailey M, McKean D, Shulman JM, De Jager PL, Chibnik L, Bennett DA, Fagan AN, Holtzman DM, Morris JC, the Alzheimer Disease Genetic Consortium (ADGC), Alzheimer’s Disease Neuroimaging Initiative (ADNI), the GERAD Consortium, and Alison M. Goate. GWAS of cerebrospinal fluid tau levels identifies novel risk variants for Alzheimer’s disease. Neuron. 2013 Apr 24;78(2):256-68. PMID: 23562540. PMCID: PMC3664945

Last Updated: 7/24/2014 11:53:41 AM

Back To Top

Follow us: