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Dr Rebecca Sims
Research Fellow, Division of Psychological Medicine and Clinical Neurosciences
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Identifying Risk Genes for Common Alzheimer's disease
I use large scale genome-wide association and sequencing studies to identify genes that affect an individual's risk of developing late-onset Alzheimer’s disease.
I am a neurogeneticist with over ten years experience in neurodegeneration research. I have a particular interest in the generation of large-scale powerful datasets and data analysis. I have significant experience of International collaboration, maintaining networks and producing high quality publications. My recent work has included leading genome-wide association projects, such as exome chip array studies. My current work focuses on the translation of genetic findings to disease relevant induced pluripotent cell models, and utilizes Next Generation Sequencing (NGS) technology to identify novel risk loci for early-onset Alzheimer’s disease.
Cyhoeddiad
2024
- Le Borgne, J. et al. 2024. Association of MGMT and BIN1 genes with Alzheimer's disease risk across sex and APOE ε4 status. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 20(3), pp. 2282-2284. (10.1002/alz.13550)
2023
- Ray, N. R. et al. 2023. The early-onset Alzheimer's disease whole-genome sequencing project: Study design and methodology. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 19(9), pp. 4187-4195. (10.1002/alz.13370)
- Le Guen, Y. et al. 2023. Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes. Proceedings of the National Academy of Sciences 120(36), article number: e2302720120. (10.1073/pnas.2302720120)
- Veteleanu, A. et al. 2023. Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels. Journal of Neuroinflammation 20(1), article number: 169. (10.1186/s12974-023-02850-6)
- Luo, J. et al. 2023. Genetic associations between modifiable risk factors and Alzheimer disease. Jama Network Open 6(5), article number: e2313734. (10.1001/jamanetworkopen.2023.13734)
- Somogyi, A. et al. 2023. The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system. Journal of Cell Science 136(6), article number: jcs259875. (10.1242/jcs.259875)
- Stevenson-Hoare, J. et al. 2023. Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease. Brain 146(2), pp. 690-699. (10.1093/brain/awac128)
2022
- Guen, Y. L. et al. 2022. Protective association of HLA-DRB1*04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 18(S3), article number: e060159. (10.1002/alz.060159)
- Guen, Y. L. et al. 2022. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE-ε4. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 18(S4), article number: e060114. (10.1002/alz.060114)
- Stevenson-Hoare, J. O. et al. 2022. Blood plasma biomarkers improve prediction accuracy over and above genetic predictors of Alzheimer's disease [Abstract]. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 18(S6), article number: e064192. (10.1002/alz.064192)
- Coad, B., Ghomroudi, P. A., Sims, R., Aggleton, J., Vann, S. D. and Metzler-Baddeley, C. 2022. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. Neurobiology of Aging 113, pp. 39-54. (10.1016/j.neurobiolaging.2022.02.004)
- Bellenguez, C. et al. 2022. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nature Genetics 54(4), pp. 412-436. (10.1038/s41588-022-01024-z)
- Madrid, L. et al. 2022. Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis. Aging 13(7), pp. 9277-9329. (10.18632/aging.202950)
- Belloy, M. E. et al. 2022. Challenges at the APOE locus: a robust quality control approach for accurate APOE genotyping. Alzheimer's Research and Therapy 14, article number: 22. (10.1186/s13195-022-00962-4)
2021
- Torvell, M., Carpanini, S. M., Daskoulidou, N., Byrne, R. A. J., Sims, R. and Morgan, B. P. 2021. Genetic insights into the impact of complement in Alzheimer's disease. Genes 12(12), article number: 1990. (10.3390/genes12121990)
- Coad, B. M., Ghomroudi, P. A., Sims, R., Aggleton, J. P., Vann, S. D. and Metzler-Baddeley, C. 2021. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. [Online]. bioRxiv. Available at: https://doi.org/10.1101/2021.11.12.468385
- DeMichele-Sweet, M. A. A. et al. 2021. Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Molecular Psychiatry 26(10), pp. 5797-5811. (10.1038/s41380-021-01152-8)
- Maguire, E. et al. 2021. PIP2 depletion and altered endocytosis caused by expression of Alzheimer's disease-protective variant PLCγ2 R522. EMBO Journal 40(17), article number: e105603. (10.15252/embj.2020105603)
- de Rojas, I. et al. 2021. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nature Communications 12(1), article number: 3417. (10.1038/s41467-021-22491-8)
- Harwood, J., Leonenko, G., Sims, R., Escott-Price, V., Williams, J. and Holmans, P. 2021. Defining functional variants associated with Alzheimer's disease in the induced immune response. Brain Communications 3(2), article number: fcab083. (10.1093/braincomms/fcab083)
- Carpanini, S. M., Harwood, J. C., Baker, E., Torvell, M., Sims, R., Williams, J. and Morgan, B. P. 2021. The impact of complement genes on the risk of late-onset Alzheimer's disease. Genes 12(3), article number: 443. (10.3390/genes12030443)
- Raybould, R. and Sims, R. 2021. Searching the dark genome for Alzheimer's disease risk variants. Brain Sciences 11(3), article number: 332. (10.3390/brainsci11030332)
- Katzourou, I. et al. 2021. Cognitive decline in Alzheimer’s disease is not associated with APOE. Journal of Alzheimer's Disease 84(1), pp. 141-149. (10.3233/jad-210685)
2020
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Hamilton, D. A., Kidd, E. and Metzler-Baddeley, C. 2020. Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults. Neurobiology of Aging 94, pp. 298-310. (10.1016/j.neurobiolaging.2020.06.014)
- Hannon, E. et al. 2020. Genetic risk for Alzheimer’s disease influences neuropathology via multiple biological pathways. Brain Communications 2(2), article number: fcaa167. (10.1093/braincomms/fcaa167)
- Holstege, H. et al. 2020. Exome sequencing identifies novel AD-associated genes. [Online]. medRxiv. (10.1101/2020.07.22.20159251) Available at: http://dx.doi.org/10.1101/2020.07.22.20159251
- Sims, R., Hill, M. and Williams, J. 2020. The multiplex model of the genetics of Alzheimer’s disease. Nature Neuroscience 23, pp. 311-322. (10.1038/s41593-020-0599-5)
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Kidd, E., Aggleton, J. and Metzler-Baddeley, C. 2020. APOE-e4-related differences in left thalamic microstructure in cognitively healthy adults. Scientific Reports 10, article number: 19787. (10.1038/s41598-020-75992-9)
2019
- Leonenko, G. et al. 2019. Genetic risk for Alzheimer's disease is distinct from genetic risk for amyloid deposition. Annals of Neurology 86(3), pp. 427-435. (10.1002/ana.25530)
- Baker, E. et al. 2019. Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease. PLoS ONE 14(7), article number: e0218111. (10.1371/journal.pone.0218111)
- Lancaster, T. M., Hill, M. J., Sims, R. and Williams, J. 2019. Microglia - mediated immunity partly contributes to the genetic association between Alzheimer's disease and hippocampal volume. Brain, Behavior, and Immunity 79, pp. 267-273. (10.1016/j.bbi.2019.02.011)
- Metzler-Baddeley, C. et al. 2019. Sex-specific effects of central adiposity and inflammatory markers on limbic microstructure. NeuroImage 189, pp. 793-803. (10.1016/j.neuroimage.2019.02.007)
- Kunkle, B. W. et al. 2019. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nature Genetics 51(3), pp. 414-430. (10.1038/s41588-019-0358-2)
- Leonenko, G. et al. 2019. Polygenic risk and hazard scores for Alzheimer's disease prediction. Annals of Clinical and Translational Neurology 6(3), pp. 456-465. (10.1002/acn3.716)
- Grozeva, D., Saad, S., Menzies, G. E. and Sims, R. 2019. Benefits and challenges of rare genetic variation in Alzheimer's disease. Current Genetic Medicine Reports 7(1), pp. 53-62. (10.1007/s40142-019-0161-5)
- Metzler-Baddeley, C. et al. 2019. Fornix white matter glia damage causes hippocampal gray matter damage during age-dependent limbic decline. Scientific Reports 9, article number: 1060. (10.1038/s41598-018-37658-5)
- Hodgetts, C. J. et al. 2019. Increased posterior default mode network activity and structural connectivity in young adult APOE-ε4 carriers: a multi-modal imaging investigation. Neurobiology of Aging 73, pp. 82-91. (10.1016/j.neurobiolaging.2018.08.026)
2018
- Gusareva, E. S. et al. 2018. Male-specific epistasis between WWC1 and TLN2 genes is associated with Alzheimer's disease. Neurobiology of Aging 72, pp. e3-e12., article number: 188. (10.1016/j.neurobiolaging.2018.08.001)
- Ahmad, S. et al. 2018. Disentangling the biological pathways involved in early features of Alzheimer's disease in the Rotterdam Study. Alzheimer's and Dementia 14(7), pp. 848-857. (10.1016/j.jalz.2018.01.005)
- Baker, E., Schmidt, K. M., Sims, R., O'Donovan, M. C., Williams, J., Holmans, P. and Escott-Price, V. 2018. POLARIS: polygenic LD-adjusted risk score approach for set-based analysis of GWAS data. Genetic Epidemiology 42(4), pp. 366-377. (10.1002/gepi.22117)
- Rao, S. et al. 2018. An APOE-independent cis-eSNP on chromosome 19q13.32 influences tau levels and late-onset Alzheimer's disease risk. Neurobiology of Aging 66, pp. 178-178., article number: e1-e8. (10.1016/j.neurobiolaging.2017.12.027)
- DeMichele-Sweet, M. A. A. et al. 2018. Genetic risk for schizophrenia and psychosis in Alzheimer disease. Molecular Psychiatry 23, pp. 963-972. (10.1038/mp.2017.81)
- Sims, R. et al. 2018. Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing. [Online]. bioRxiv. (10.1101/294629) Available at: https://doi.org/10.1101/294629
2017
- Blauwendraat, C. et al. 2017. NeuroChip, an updated version of the NeuroX genotyping platform to rapidly screen for variants associated with neurological diseases. Neurobiology of Aging 57, pp. 247-247., article number: e9-e13. (10.1016/j.neurobiolaging.2017.05.009)
- Sims, R. et al. 2017. Rare coding variants in PLCG2, ABI3 and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nature Genetics 49, pp. 1373-1384. (10.1038/ng.3916)
- Morgan, A. et al. 2017. The correlation between inflammatory biomarkers and polygenic risk score in Alzheimer's Disease. Journal of Alzheimer's Disease 56(1), pp. 25-36. (10.3233/JAD-160889)
2016
- Jakobsdottir, J. et al. 2016. Rare functional variant in TM2D3 is associated with late-onset Alzheimer's disease. PLoS Genetics 12(10), article number: e1006327. (10.1371/journal.pgen.1006327)
- Scott, R. A. et al. 2016. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Science Translational Medicine 8(341), article number: 341ra76. (10.1126/scitranslmed.aad3744)
- Sims, R. and Williams, J. 2016. Defining the genetic architecture of Alzheimer's Disease: where next. Neurodegenerative Diseases 16(1-2) (10.1159/000440841)
2015
- Escott-Price, V. et al. 2015. Common polygenic variation enhances risk prediction for Alzheimer's disease. Brain 138(12), pp. 3673-3684. (10.1093/brain/awv268)
- Lancaster, T. M. et al. 2015. Alzheimer's disease risk variant in CLU is associated with neural inefficiency in healthy individuals. Alzheimer's and Dementia 11(10), pp. 1144-1152. (10.1016/j.jalz.2014.10.012)
- Jones, L. et al. 2015. Convergent genetic and expression data implicate immunity in Alzheimer's disease. Alzheimer's and Dementia 11(6), pp. 658-671. (10.1016/j.jalz.2014.05.1757)
- Østergaard, S. D. et al. 2015. Associations between potentially modifiable risk factors and Alzheimer disease: A mendelian randomization study. PLOS MEDICINE 12(6), pp. e1001841., article number: e1001841. (10.1371/journal.pmed.1001841)
- Desikan, R. S. et al. 2015. Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer Disease. Circulation 131(23), pp. 2061-2069. (10.1161/CIRCULATIONAHA.115.015489)
2014
- Proitsi, P. et al. 2014. Alleles that increase risk for type 2 diabetes mellitus are not associated with increased risk for Alzheimer's disease. Neurobiology of Aging 35(12), article number: 2883.e3. (10.1016/j.neurobiolaging.2014.07.023)
- Escott-Price, V. et al. 2014. Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease. PLoS ONE 9(6), article number: e94661. (10.1371/journal.pone.0094661)
- Mok, K. Y. et al. 2014. Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome. Neurobiology of Aging 35(6), pp. 1513.e1-5. (10.1016/j.neurobiolaging.2013.12.022)
- Benitez, B. A. et al. 2014. Missense variant in TREML2 protects against Alzheimer's disease. Neurobiology of Aging 35(6), pp. 1510.e19-26. (10.1016/j.neurobiolaging.2013.12.010)
- Hinney, A. et al. 2014. Genetic variation at theCELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 165(4), pp. 283-293. (10.1002/ajmg.b.32234)
- Ruiz, A. et al. 2014. Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene. Translational Psychiatry 4, article number: e358. (10.1038/tp.2014.2)
2013
- Lambert, J. et al. 2013. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease [Letter]. Nature Genetics 45(12), pp. 1452-1458. (10.1038/ng.2802)
- Zou, F. et al. 2013. Linking protective GAB2 variants, increased cortical GAB2 expression and decreased Alzheimer's Disease pathology. PLoS ONE 8(5), article number: e64802. (10.1371/journal.pone.0064802)
- Cruchaga, C. et al. 2013. GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease. Neuron 78(2), pp. 256-268. (10.1016/j.neuron.2013.02.026)
- Lambert, J. C. et al. 2013. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease [Correction]. Molecular Psychiatry 18(4), pp. 521. (10.1038/mp.2012.75)
- Chapman, J. et al. 2013. A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer's disease risk. Human Molecular Genetics 22(4), pp. 816-824. (10.1093/hmg/dds476)
- Jones, E. L., Mok, K., Hanney, M., Harold, D., Sims, R., Williams, J. and Ballard, C. 2013. Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome. Neurobiology of Aging 34(10), pp. 2441. (10.1016/j.neurobiolaging.2013.03.018)
2012
- Hollingworth, P. et al. 2012. Genome-wide association study of Alzheimer's disease with psychotic symptoms. Molecular Psychiatry 17(12), pp. 1316-1327. (10.1038/mp.2011.125)
- Hamilton, G. et al. 2012. The role of ECE1 variants in cognitive ability in old age and Alzheimer's disease risk. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 159B(6), pp. 696-709. (10.1002/ajmg.b.32073)
- Shi, H. et al. 2012. Genetic variants influencing human aging from late-onset Alzheimer's disease (LOAD) genome-wide association studies (GWAS). Neurobiology of Aging 33(8), article number: 1849.e5. (10.1016/j.neurobiolaging.2012.02.014)
- Hamilton, G. et al. 2012. Functional and genetic analysis of haplotypic sequence variation at the nicastrin genomic locus. Neurobiology of Aging 33(8), article number: 1848.e1. (10.1016/j.neurobiolaging.2012.02.005)
- Hudson, G. et al. 2012. No consistent evidence for association between mtDNA variants and Alzheimer disease. Neurology 78(14), pp. 1038-1042. (10.1212/WNL.0b013e31824e8f1d)
- Lambert, J. C. et al. 2012. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. Molecular Psychiatry 18, pp. 461-470. (10.1038/mp.2012.14)
- Gerrish, A. et al. 2012. The role of variation at AβPP, PSEN1, PSEN2, and MAPT in late onset Alzheimer's Disease. Journal of Alzheimer's Disease 28(2), pp. 377-387. (10.3233/JAD-2011-110824)
2011
- Hollingworth, P. et al. 2011. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease. Nature Genetics 43(5), pp. 429-435. (10.1038/ng.803)
- Sims, R. et al. 2011. No evidence that extended tracts of homozygosity are associated with Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156(7), pp. 764-771. (10.1002/ajmg.b.31216)
- Green, E. K. et al. 2011. DISC1 exon 11 rare variants found more commonly in schizoaffective spectrum cases than controls. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156B(4), pp. 490-492. (10.1002/ajmg.b.31187)
2010
- Jones, L. et al. 2010. Genetic evidence implicates the immune system and cholesterol metabolism in the aetiology of Alzheimer's disease. PLoS ONE 5(11), article number: e13950. (10.1371/journal.pone.0013950)
- Lupton, M. K. et al. 2010. Education, occupation and retirement age effects on the age of onset of Alzheimer's disease. International Journal of Geriatric Psychiatry 25(1), pp. 30-36. (10.1002/gps.2294)
2009
- Harold, D. et al. 2009. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease [Letter]. Nature Genetics 41(10), pp. 1088-1093. (10.1038/ng.440)
- Harold, D. et al. 2009. Erratum: Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease [Corrigendum]. Nature Genetics 41(10), pp. 1156. (10.1038/ng1009-1156d)
- Sims, R. 2009. Searching for susceptibility genes for psychosis in late-onset Alzheimer's disease. PhD Thesis, Cardiff University.
- Abraham, R. A., Sims, R., Carroll, L. S., Hollingworth, P., O'Donovan, M. C., Williams, J. and Owen, M. J. 2009. An association study of common variation at theMAPTlocus with late-onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 150B(8), pp. 1152-1155. (10.1002/ajmg.b.30951)
- Sims, R. et al. 2009. Evidence that variation in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene is associated with psychosis in Alzheimer's disease. Neuroscience Letters 461(1), pp. 54-59. (10.1016/j.neulet.2009.05.051)
2008
- Abraham, R. et al. 2008. A genome-wide association study for late-onset Alzheimer's disease using DNA pooling. BMC Medical Genomics 1(1), article number: 44. (10.1186/1755-8794-1-44)
2007
- Hollingworth, P. et al. 2007. Increased familial risk and genomewide significant linkage for Alzheimer's disease with psychosis. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144B(7), pp. 841-848. (10.1002/ajmg.b.30515)
Articles
- Le Borgne, J. et al. 2024. Association of MGMT and BIN1 genes with Alzheimer's disease risk across sex and APOE ε4 status. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 20(3), pp. 2282-2284. (10.1002/alz.13550)
- Ray, N. R. et al. 2023. The early-onset Alzheimer's disease whole-genome sequencing project: Study design and methodology. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 19(9), pp. 4187-4195. (10.1002/alz.13370)
- Le Guen, Y. et al. 2023. Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes. Proceedings of the National Academy of Sciences 120(36), article number: e2302720120. (10.1073/pnas.2302720120)
- Veteleanu, A. et al. 2023. Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels. Journal of Neuroinflammation 20(1), article number: 169. (10.1186/s12974-023-02850-6)
- Luo, J. et al. 2023. Genetic associations between modifiable risk factors and Alzheimer disease. Jama Network Open 6(5), article number: e2313734. (10.1001/jamanetworkopen.2023.13734)
- Somogyi, A. et al. 2023. The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system. Journal of Cell Science 136(6), article number: jcs259875. (10.1242/jcs.259875)
- Stevenson-Hoare, J. et al. 2023. Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease. Brain 146(2), pp. 690-699. (10.1093/brain/awac128)
- Guen, Y. L. et al. 2022. Protective association of HLA-DRB1*04 subtypes in neurodegenerative diseases implicates acetylated tau PHF6 sequences. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 18(S3), article number: e060159. (10.1002/alz.060159)
- Guen, Y. L. et al. 2022. Rare missense variant (R251G) on APOE counterbalances the Alzheimer’s disease risk associated with APOE-ε4. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 18(S4), article number: e060114. (10.1002/alz.060114)
- Stevenson-Hoare, J. O. et al. 2022. Blood plasma biomarkers improve prediction accuracy over and above genetic predictors of Alzheimer's disease [Abstract]. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 18(S6), article number: e064192. (10.1002/alz.064192)
- Coad, B., Ghomroudi, P. A., Sims, R., Aggleton, J., Vann, S. D. and Metzler-Baddeley, C. 2022. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. Neurobiology of Aging 113, pp. 39-54. (10.1016/j.neurobiolaging.2022.02.004)
- Bellenguez, C. et al. 2022. New insights into the genetic etiology of Alzheimer's disease and related dementias. Nature Genetics 54(4), pp. 412-436. (10.1038/s41588-022-01024-z)
- Madrid, L. et al. 2022. Multiomics integrative analysis identifies APOE allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis. Aging 13(7), pp. 9277-9329. (10.18632/aging.202950)
- Belloy, M. E. et al. 2022. Challenges at the APOE locus: a robust quality control approach for accurate APOE genotyping. Alzheimer's Research and Therapy 14, article number: 22. (10.1186/s13195-022-00962-4)
- Torvell, M., Carpanini, S. M., Daskoulidou, N., Byrne, R. A. J., Sims, R. and Morgan, B. P. 2021. Genetic insights into the impact of complement in Alzheimer's disease. Genes 12(12), article number: 1990. (10.3390/genes12121990)
- DeMichele-Sweet, M. A. A. et al. 2021. Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Molecular Psychiatry 26(10), pp. 5797-5811. (10.1038/s41380-021-01152-8)
- Maguire, E. et al. 2021. PIP2 depletion and altered endocytosis caused by expression of Alzheimer's disease-protective variant PLCγ2 R522. EMBO Journal 40(17), article number: e105603. (10.15252/embj.2020105603)
- de Rojas, I. et al. 2021. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. Nature Communications 12(1), article number: 3417. (10.1038/s41467-021-22491-8)
- Harwood, J., Leonenko, G., Sims, R., Escott-Price, V., Williams, J. and Holmans, P. 2021. Defining functional variants associated with Alzheimer's disease in the induced immune response. Brain Communications 3(2), article number: fcab083. (10.1093/braincomms/fcab083)
- Carpanini, S. M., Harwood, J. C., Baker, E., Torvell, M., Sims, R., Williams, J. and Morgan, B. P. 2021. The impact of complement genes on the risk of late-onset Alzheimer's disease. Genes 12(3), article number: 443. (10.3390/genes12030443)
- Raybould, R. and Sims, R. 2021. Searching the dark genome for Alzheimer's disease risk variants. Brain Sciences 11(3), article number: 332. (10.3390/brainsci11030332)
- Katzourou, I. et al. 2021. Cognitive decline in Alzheimer’s disease is not associated with APOE. Journal of Alzheimer's Disease 84(1), pp. 141-149. (10.3233/jad-210685)
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Hamilton, D. A., Kidd, E. and Metzler-Baddeley, C. 2020. Genetic risk of dementia modifies obesity effects on white matter myelin in cognitively healthy adults. Neurobiology of Aging 94, pp. 298-310. (10.1016/j.neurobiolaging.2020.06.014)
- Hannon, E. et al. 2020. Genetic risk for Alzheimer’s disease influences neuropathology via multiple biological pathways. Brain Communications 2(2), article number: fcaa167. (10.1093/braincomms/fcaa167)
- Sims, R., Hill, M. and Williams, J. 2020. The multiplex model of the genetics of Alzheimer’s disease. Nature Neuroscience 23, pp. 311-322. (10.1038/s41593-020-0599-5)
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Kidd, E., Aggleton, J. and Metzler-Baddeley, C. 2020. APOE-e4-related differences in left thalamic microstructure in cognitively healthy adults. Scientific Reports 10, article number: 19787. (10.1038/s41598-020-75992-9)
- Leonenko, G. et al. 2019. Genetic risk for Alzheimer's disease is distinct from genetic risk for amyloid deposition. Annals of Neurology 86(3), pp. 427-435. (10.1002/ana.25530)
- Baker, E. et al. 2019. Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer’s disease. PLoS ONE 14(7), article number: e0218111. (10.1371/journal.pone.0218111)
- Lancaster, T. M., Hill, M. J., Sims, R. and Williams, J. 2019. Microglia - mediated immunity partly contributes to the genetic association between Alzheimer's disease and hippocampal volume. Brain, Behavior, and Immunity 79, pp. 267-273. (10.1016/j.bbi.2019.02.011)
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- Baker, E., Schmidt, K. M., Sims, R., O'Donovan, M. C., Williams, J., Holmans, P. and Escott-Price, V. 2018. POLARIS: polygenic LD-adjusted risk score approach for set-based analysis of GWAS data. Genetic Epidemiology 42(4), pp. 366-377. (10.1002/gepi.22117)
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- Sims, R. et al. 2017. Rare coding variants in PLCG2, ABI3 and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nature Genetics 49, pp. 1373-1384. (10.1038/ng.3916)
- Morgan, A. et al. 2017. The correlation between inflammatory biomarkers and polygenic risk score in Alzheimer's Disease. Journal of Alzheimer's Disease 56(1), pp. 25-36. (10.3233/JAD-160889)
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- Sims, R. and Williams, J. 2016. Defining the genetic architecture of Alzheimer's Disease: where next. Neurodegenerative Diseases 16(1-2) (10.1159/000440841)
- Escott-Price, V. et al. 2015. Common polygenic variation enhances risk prediction for Alzheimer's disease. Brain 138(12), pp. 3673-3684. (10.1093/brain/awv268)
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- Desikan, R. S. et al. 2015. Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer Disease. Circulation 131(23), pp. 2061-2069. (10.1161/CIRCULATIONAHA.115.015489)
- Proitsi, P. et al. 2014. Alleles that increase risk for type 2 diabetes mellitus are not associated with increased risk for Alzheimer's disease. Neurobiology of Aging 35(12), article number: 2883.e3. (10.1016/j.neurobiolaging.2014.07.023)
- Escott-Price, V. et al. 2014. Gene-wide analysis detects two new susceptibility genes for Alzheimer's Disease. PLoS ONE 9(6), article number: e94661. (10.1371/journal.pone.0094661)
- Mok, K. Y. et al. 2014. Polymorphisms in BACE2 may affect the age of onset Alzheimer's dementia in Down syndrome. Neurobiology of Aging 35(6), pp. 1513.e1-5. (10.1016/j.neurobiolaging.2013.12.022)
- Benitez, B. A. et al. 2014. Missense variant in TREML2 protects against Alzheimer's disease. Neurobiology of Aging 35(6), pp. 1510.e19-26. (10.1016/j.neurobiolaging.2013.12.010)
- Hinney, A. et al. 2014. Genetic variation at theCELF1 (CUGBP, elav-like family member 1 gene) locus is genome-wide associated with Alzheimer's disease and obesity. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 165(4), pp. 283-293. (10.1002/ajmg.b.32234)
- Ruiz, A. et al. 2014. Follow-up of loci from the International Genomics of Alzheimer's Disease Project identifies TRIP4 as a novel susceptibility gene. Translational Psychiatry 4, article number: e358. (10.1038/tp.2014.2)
- Lambert, J. et al. 2013. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease [Letter]. Nature Genetics 45(12), pp. 1452-1458. (10.1038/ng.2802)
- Zou, F. et al. 2013. Linking protective GAB2 variants, increased cortical GAB2 expression and decreased Alzheimer's Disease pathology. PLoS ONE 8(5), article number: e64802. (10.1371/journal.pone.0064802)
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- Lambert, J. C. et al. 2013. Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease [Correction]. Molecular Psychiatry 18(4), pp. 521. (10.1038/mp.2012.75)
- Chapman, J. et al. 2013. A genome-wide study shows a limited contribution of rare copy number variants to Alzheimer's disease risk. Human Molecular Genetics 22(4), pp. 816-824. (10.1093/hmg/dds476)
- Jones, E. L., Mok, K., Hanney, M., Harold, D., Sims, R., Williams, J. and Ballard, C. 2013. Evidence that PICALM affects age at onset of Alzheimer's dementia in Down syndrome. Neurobiology of Aging 34(10), pp. 2441. (10.1016/j.neurobiolaging.2013.03.018)
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- Sims, R. et al. 2011. No evidence that extended tracts of homozygosity are associated with Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156(7), pp. 764-771. (10.1002/ajmg.b.31216)
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- Abraham, R. A., Sims, R., Carroll, L. S., Hollingworth, P., O'Donovan, M. C., Williams, J. and Owen, M. J. 2009. An association study of common variation at theMAPTlocus with late-onset Alzheimer's disease. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 150B(8), pp. 1152-1155. (10.1002/ajmg.b.30951)
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Thesis
- Sims, R. 2009. Searching for susceptibility genes for psychosis in late-onset Alzheimer's disease. PhD Thesis, Cardiff University.
Websites
- Coad, B. M., Ghomroudi, P. A., Sims, R., Aggleton, J. P., Vann, S. D. and Metzler-Baddeley, C. 2021. Apolipoprotein ε4 modifies obesity-related atrophy in the hippocampal formation of cognitively healthy adults. [Online]. bioRxiv. Available at: https://doi.org/10.1101/2021.11.12.468385
- Holstege, H. et al. 2020. Exome sequencing identifies novel AD-associated genes. [Online]. medRxiv. (10.1101/2020.07.22.20159251) Available at: http://dx.doi.org/10.1101/2020.07.22.20159251
- Sims, R. et al. 2018. Meta-analysis of genetic association with diagnosed Alzheimer's disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing. [Online]. bioRxiv. (10.1101/294629) Available at: https://doi.org/10.1101/294629
Ymchwil
My research identifies susceptibility genes for Alzheimer's disease. I have a particular interest in analysing rare frequency genetic variation and my recent work implicates immune cells, specifically microglia in disease development.
Funding
2015-2018 JOINT PROGRAMME FOR NEURODEGENERATIVE DISEASE
"A European AD DNA bank (EADB)" (UK-PI: 1,599,069€)
2016-2018 CENTRES OF EXCELLENCE IN NEURODEGENERATION
"Therapeutic targeting of impaired lysosomal flux in Alzheimer’s disease" (Co-PI: £284,126)
2015 MOONDANCE FOUNDATION
“Moondance Centre for Young-onset Dementia” (Co-PI: £500,00)
2015 WELSH GOVERNMENT STRATEGIC AWARD
“Purchase of MassArray Genotyping Platform” (PI: £115,517)
2012-2016 ALZHEIMER’S SOCIETY RESEARCH FELLOWSHIP.
“Powerful Study of Rare Variants in Alzheimer’s disease” (PI: £200,000).
Bywgraffiad
EMPLOYMENT
2016–ongoing CARDIFF UNIVERSITY, SCHOOL OF MEDICINE.
Tenured Fast Track Fellow
2012–Present CARDIFF UNIVERSITY, SCHOOL OF MEDICINE.
Research Fellow.
Funded by Alzheimer’s Society Fellowship Award.
2010–2012 CARDIFF UNIVERSITY, SCHOOL OF MEDICINE.
Research Associate in the department of Psychological Medicine.
Funded via MRC Programme Grant.
FURTHER EDUCATION
2012-Present CARDIFF UNIVERSITY, SCHOOL OF MEDICINE.
MSc Genetic Epidemiology and Bioinformatics
2005-2009 CARDIFF UNIVERSITY, SCHOOL OF MEDICINE.
PhD “The genetics of Alzheimer’s disease with psychosis.”
2001-2005 CARDIFF UNIVERSITY, SCHOOL OF BIOSCIENCES.
BSc Genetics (2.1)
Anrhydeddau a dyfarniadau
CONFERENCE PRESENTATIONS
Alzheimer’s Society 2015 Oral presentation: Studying Alzheimer’s Genetics using Rare Variant Microarrays
AAIC 2015 Poster presentation: Powerful Study of Rare Variation in Alzheimer’s disease
BNA 2015 Oral presentation: Advances in Alzheimer’s Genetics
AAIC 2012 Poster presentation: Follow up of Alzheimer’s disease with psychosis genome-wide association studies
AAIC 2011 Poster presentation: No consistent evidence for association between mtDNA variants and Alzheimer disease
ESHG 2011 Poster presentation: Investigating Runs of Homozygosity in Alzheimer’s disease
ICAD 2010 Poster presentation: Mitochondrial Genome-Wide Association Study of Alzheimer’s disease
ICAD 2009 Poster presentation: Investigating psychosis candidate genes in Alzheimer’s disease with psychosis using genome-wide association (GWA) studies.
Wellcome Trust 2009 Oral and Poster presentation: Genome Wide Association Study for Alzheimer’s disease with Psychotic Symptoms
ASHG 2008 Poster presentation: Oligodendrocyte Lineage Transcription Factor 2 (OLIG2) and association with Psychosis In Alzheimer’s disease
ICAD 2008 Poster presentation: Testing for association between Alzheimer’s disease with psychosis and variants identified as influencing risk of schizophrenia
Aelodaethau proffesiynol
Member of the Genetics Society
Contact Details
SimsRC@caerdydd.ac.uk
+44 29206 88450
Adeilad Hadyn Ellis, Ystafell 1.03 - Office F, Heol Maendy, Caerdydd, CF24 4HQ
+44 29206 88450
Adeilad Hadyn Ellis, Ystafell 1.03 - Office F, Heol Maendy, Caerdydd, CF24 4HQ
