Aree Widya Witoelar

Forsker - Gruppe for Neural Computation

English version of this page

E-post a.w.witoelar@medisin.uio.no

Rom 0300

Brukernavn

Besøksadresse Sognsvannsveien 9 Domus Medica 0372 Oslo

Postadresse Postboks 1103 Blindern 0317 Oslo

Last ned visittkort

Faglige interesser

I am interested in (1) modelling neural processes in the cerebral cortex and (2) developing statistical machine learning to uncover structures in neural data.

Undervisning

2018-present Forsker, University of Oslo
2017-2018 Forsker, Oslo University Hospital
2014-2017 Postdoc, University of Oslo
2010-2014 Postdoc, Kavli Institute for Systems Neuroscience, NTNU
2005-2010 Ph.D., Machine Learning, University of Groningen
2002-2005 M.Sc., Physics, University of Groningen

Priser

Marie Curie Career Development of Researchers (2016)
Ubbo Emmius scholarship for doctoral studies (2005)

Emneord: Machine learning, Neuroscience, Statistics, Computational Biology

Hennestad, Eivind; Witoelar, Aree Widya; Chambers, Anna Ruth & Vervaeke, Koen Gerard Alois (2021). Mapping vestibular and visual contributions to angular head velocity tuning in the cortex. Cell reports. ISSN 2211-1247. 37(12). doi: 10.1016/j.celrep.2021.110134. Fulltekst i vitenarkiv
Rongve, Arvid; Witoelar, Aree; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla & Clarimon, Jordi [Vis alle 40 forfattere av denne artikkelen] (2019). GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study. Scientific Reports. ISSN 2045-2322. 9. doi: 10.1038/s41598-019-43458-2. Fulltekst i vitenarkiv
Drange, Ole Kristian; Smeland, Olav Bjerkehagen; Shadrin, Alexey A.; Finseth, Per Ivar; Witoelar, Aree & Frei, Oleksandr [Vis alle 52 forfattere av denne artikkelen] (2019). Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. Frontiers in Neuroscience. ISSN 1662-4548. 13. doi: 10.3389/fnins.2019.00220. Fulltekst i vitenarkiv Vis sammendrag
Background: Alzheimer’s disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer’s Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.
Jansen, Iris E.; Savage, Jeanne E.; Watanabe, Kyoko; Bryois, Julien; Williams, Dylan M. & Steinberg, Stacy [Vis alle 53 forfattere av denne artikkelen] (2019). Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk. Nature Genetics. ISSN 1061-4036. 51(3), s. 404–413. doi: 10.1038/s41588-018-0311-9. Fulltekst i vitenarkiv
Broce, Iris J.; Tan, Chin Hong; Fan, CC; Jansen, Iris E.; Savage, Jeanne E. & Witoelar, Aree [Vis alle 34 forfattere av denne artikkelen] (2018). Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer's disease. Acta Neuropathologica. ISSN 0001-6322. doi: 10.1007/s00401-018-1928-6.
Witoelar, Aree; Rongve, Arvid; Almdahl, Ina Selseth; Ulstein, Ingun; Engvig, Andreas & White, Linda Rosemary [Vis alle 33 forfattere av denne artikkelen] (2018). Meta-analysis of Alzheimer’s disease on 9,751 samples from Norway and IGAP study identifies four risk loci. Scientific Reports. ISSN 2045-2322. 8. doi: 10.1038/s41598-018-36429-6. Fulltekst i vitenarkiv
Bettella, Francesco; Brown, AA; Smeland, Olav Bjerkehagen; Wang, Yunpeng; Witoelar, Aree & Buil Demur, AA [Vis alle 11 forfattere av denne artikkelen] (2018). Cross-tissue eQTL enrichment of associations in schizophrenia. PLOS ONE. ISSN 1932-6203. 13(9). doi: 10.1371/journal.pone.0202812. Fulltekst i vitenarkiv
Srinivasan, Saurabh; Bettella, Francesco; Frei, Oleksandr; Hill, W. David; Wang, Yunpeng & Witoelar, Aree [Vis alle 17 forfattere av denne artikkelen] (2018). Enrichment of genetic markers of recent human evolution in educational and cognitive traits. Scientific Reports. ISSN 2045-2322. 8:12585, s. 1–9. doi: 10.1038/s41598-018-30387-9. Fulltekst i vitenarkiv
Zuber, Verena; Jönsson, Erik Gunnar; Frei, Oleksandr; Witoelar, Aree; Thompson, Wesley Kurt & Schork, Andrew J. [Vis alle 18 forfattere av denne artikkelen] (2018). Identification of shared genetic variants between schizophrenia and lung cancer. Scientific Reports. ISSN 2045-2322. 674(8), s. 1–8. doi: 10.1038/s41598-017-16481-4. Fulltekst i vitenarkiv
Shadrin, Alexey A.; Smeland, Olav Bjerkehagen; Zayats, Tetyana; Schork, Andrew J; Frei, Oleksandr & Bettella, Francesco [Vis alle 19 forfattere av denne artikkelen] (2017). Novel loci associated with attention-deficit/hyperactivity disorder are revealed by leveraging polygenic overlap with educational attainment. Journal of the American Academy of Child and Adolescent Psychiatry. ISSN 0890-8567. 57(2), s. 86–95. doi: 10.1016/j.jaac.2017.11.013. Fulltekst i vitenarkiv
Winsvold, Bendik K S; Bettella, Francesco; Witoelar, Aree; Anttila, Verneri; Gormley, Padhraig & Kurth, Tobias [Vis alle 18 forfattere av denne artikkelen] (2017). Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants. PLOS ONE. ISSN 1932-6203. s. 1–15. doi: 10.1371/journal.pone.0185663. Fulltekst i vitenarkiv
Smeland, Olav Bjerkehagen; Wang, Yunpeng; Frei, Oleksandr; Li, Wen; Hibar, Derrek P & Franke, Barbara [Vis alle 13 forfattere av denne artikkelen] (2017). Genetic overlap between schizophrenia and volumes of hippocampus, putamen, and intracranial volume indicates shared molecular genetic mechanisms. Schizophrenia Bulletin. ISSN 0586-7614. 44(4), s. 854–864. doi: 10.1093/schbul/sbx148.
Smeland, Olav Bjerkehagen; Frei, Oleksandr; Kauppi, Karolina; Hill, W. David; Li, Wen & Wang, Yunpeng [Vis alle 22 forfattere av denne artikkelen] (2017). Identification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive function. JAMA psychiatry. ISSN 2168-6238. 74(10), s. 1065–1075. doi: 10.1001/jamapsychiatry.2017.1986. Fulltekst i vitenarkiv
Zuber, Verena; Bettella, Francesco; Witoelar, Aree; Andreassen, Ole Andreas; Mills, Ian Geoffrey & Urbanucci, Alfonso (2017). Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer. BMC Genomics. ISSN 1471-2164. 18:270, s. 1–11. doi: 10.1186/s12864-017-3620-y. Fulltekst i vitenarkiv
Desikan, Rahul S.; Fan, Chun Chieh; Wang, Yunpeng; Schork, Andrew J; Cabral, Howard J & Cupples, L. Adrienne [Vis alle 34 forfattere av denne artikkelen] (2017). Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score. Nature Methods. ISSN 1548-7091. 14(3:e1002258), s. 1–17. doi: 10.1371/journal.pmed.1002258.
Witoelar, Aree; Jansen, Iris E.; Wang, Yunpeng; Desikan, Rahul S.; Gibbs, J. Raphael & Thompson, Wesley Kurt [Vis alle 26 forfattere av denne artikkelen] (2017). Genome-wide pleiotropy between Parkinson disease and autoimmune diseases. JAMA Neurology. ISSN 2168-6149. 74(7), s. 780–792. doi: 10.1001/jamaneurol.2017.0469.
Ferrari, Raffaele; Wang, Yunpeng; Vandrovcova, Jana; Guelfi, Sebastian; Witoelar, Aree & Karch, Celeste M. [Vis alle 22 forfattere av denne artikkelen] (2017). Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimer's and Parkinson's diseases. Journal of Neurology, Neurosurgery and Psychiatry. ISSN 0022-3050. 88(2), s. 152–164. doi: 10.1136/jnnp-2016-314411.
Devor, Anna; Andreassen, Ole Andreas; Wang, Yunpeng; Mäki-Marttunen, Tuomo; Smeland, Olav Bjerkehagen & Fan, Chun Chieh [Vis alle 18 forfattere av denne artikkelen] (2017). Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia. Molecular Psychiatry. ISSN 1359-4184. 22(6), s. 792–801. doi: 10.1038/mp.2017.33. Fulltekst i vitenarkiv
Smeland, Olav Bjerkehagen; Wang, Yunpeng; Lo, Min-Tzu; Li, Wen; Frei, Oleksandr & Witoelar, Aree [Vis alle 13 forfattere av denne artikkelen] (2017). Identification of genetic loci shared between schizophrenia and the Big Five personality traits. Scientific Reports. ISSN 2045-2322. 7:2222(1), s. 1–9. doi: 10.1038/s41598-017-02346-3. Fulltekst i vitenarkiv
Srinivasan, Saurabh; Bettella, Francesco; Hassani, Sahar; Wang, Yunpeng; Witoelar, Aree & Schork, Andrew J. [Vis alle 13 forfattere av denne artikkelen] (2017). Probing the association between early evolutionary markers and schizophrenia. PLOS ONE. ISSN 1932-6203. 12:e0169227(1), s. 1–15. doi: 10.1371/journal.pone.0169227.
Le Hellard, Stephanie; Wang, Yunpeng; Witoelar, Aree; Zuber, Verena; Bettella, Francesco & Hugdahl, Kenneth [Vis alle 15 forfattere av denne artikkelen] (2017). Identification of gene loci that overlap between schizophrenia and educational attainment. Schizophrenia Bulletin. ISSN 0586-7614. 43(3), s. 654–664. doi: 10.1093/schbul/sbw085.
Yokoyama, Jennifer S.; Wang, Yunpeng; Schork, Andrew J.; Thompson, Wesley K.; Karch, Celeste M. & Cruchaga, Carlos [Vis alle 28 forfattere av denne artikkelen] (2016). Association between genetic traits for immune-mediated diseases and Alzheimer disease. JAMA Neurology. ISSN 2168-6149. 73(6), s. 691–697. doi: 10.1001/jamaneurol.2016.0150.
Wang, Yunpeng; Bos, Steffan Daniel; Harbo, Hanne Flinstad; Thompson, Wesley K.; Schork, Andrew J. & Bettella, Francesco [Vis alle 14 forfattere av denne artikkelen] (2016). Genetic overlap between multiple sclerosis and several cardiovascular disease risk factors. Multiple Sclerosis. ISSN 1352-4585. 22(14), s. 1783–1793. doi: 10.1177/1352458516635873.
Holland, Dominic; Wang, Yunpeng; Thompson, Wesley K.; Schork, Andrew J.; Chen, Chi-Hua & Lo, Min-Tzu [Vis alle 11 forfattere av denne artikkelen] (2016). Estimating effect sizes and expected replication probabilities from GWAS summary statistics. Frontiers in Genetics. ISSN 1664-8021. 7(15). doi: 10.3389/fgene.2016.00015.
Wang, Yunpeng; Thompson, Wesley K.; Schork, Andrew J.; Holland, Dominic; Chen, Chi-Hua & Bettella, Francesco [Vis alle 22 forfattere av denne artikkelen] (2016). Leveraging Genomic Annotations and Pleiotropic Enrichment for Improved Replication Rates in Schizophrenia GWAS. PLoS Genetics. ISSN 1553-7390. doi: 10.1371/journal.pgen.1005803. Fulltekst i vitenarkiv
Mäki-Marttunen, Tuomo; Halnes, Geir; Devor, Anna; Witoelar, Aree; Bettella, Francesco & Djurovic, Srdjan [Vis alle 10 forfattere av denne artikkelen] (2016). Functional effects of schizophrenia-linked genetic variants on intrinsic single-neuron excitability: a modeling study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. ISSN 2451-9022. 1(1), s. 49–59. doi: 10.1016/j.bpsc.2015.09.002. Vis sammendrag
BACKGROUND: Recent genome-wide association studies have identified a large number of genetic risk factors for schizophrenia (SCZ) featuring ion channels and calcium transporters. For some of these risk factors, independent prior investigations have examined the effects of genetic alterations on the cellular electrical excitability and calcium homeostasis. In the present proof-of-concept study, we harnessed these experimental results for modeling of computational properties on layer V cortical pyramidal cells and identified possible common alterations in behavior across SCZ-related genes. METHODS: We applied a biophysically detailed multicompartmental model to study the excitability of a layer V pyramidal cell. We reviewed the literature on functional genomics for variants of genes associated with SCZ and used changes in neuron model parameters to represent the effects of these variants. RESULTS: We present and apply a framework for examining the effects of subtle single nucleotide polymorphisms in ion channel and calcium transporter-encoding genes on neuron excitability. Our analysis indicates that most of the considered SCZ-related genetic variants affect the spiking behavior and intracellular calcium dynamics resulting from summation of inputs across the dendritic tree. CONCLUSIONS: Our results suggest that alteration in the ability of a single neuron to integrate the inputs and scale its excitability may constitute a fundamental mechanistic contributor to mental disease, alongside the previously proposed deficits in synaptic communication and network behavior. Keywords: Biophysical modeling, Functional genomics, Genome-wide association studies, Layer V pyramidal cell, Neuron excitability, Schizophrenia
Vijayaraghavan, Swetha; Darreh-Shori, Taher; Rongve, Arvid; Berge, Guro; Sando, Sigrid Botne & White, Linda [Vis alle 11 forfattere av denne artikkelen] (2016). Association of Butyrylcholinesterase-K allele and Apolipoprotein E ε 4 allele with cognitive decline in dementia with lewy bodies and Alzheimer's disease. Journal of Alzheimer's Disease. ISSN 1387-2877. 50(2), s. 567–576. doi: 10.3233/JAD-150750.
LeBlanc, Marissa; Zuber, Verena; Kulle, Bettina; Witoelar, Aree; Zeng, Limin & Bettella, Francesco [Vis alle 26 forfattere av denne artikkelen] (2015). Identifying Novel Gene Variants in Coronary Artery Disease and Shared Genes with Several Cardiovascular Risk Factors. Circulation Research. ISSN 0009-7330. 1, s. 83–94. doi: 10.1161/CIRCRESAHA.115.306629.
Srinivasan, Saurabh; Bettella, Francesco; Mattingsdal, Morten; Wang, Yunpeng; Witoelar, Aree & Schork, AJ [Vis alle 17 forfattere av denne artikkelen] (2015). Genetic Markers of Human Evolution Are Enriched in Schizophrenia. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2015.10.009.
Thompson, WK; Wang, Yunpeng; Schork, AJ; Witoelar, Aree; Zuber, Verena & Xu, S [Vis alle 10 forfattere av denne artikkelen] (2015). An Empirical Bayes Mixture Model for Effect Size Distributions in Genome-Wide Association Studies. PLoS Genetics. ISSN 1553-7390. 11(12). doi: 10.1371/journal.pgen.1005717.
Desikan, RS; Schork, AJ; Wang, Yunpeng; Witoelar, Aree; Sharma, M & McEvoy, LK [Vis alle 45 forfattere av denne artikkelen] (2015). Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus. Molecular Psychiatry. ISSN 1359-4184. 20(12), s. 1588–1595. doi: 10.1038/mp.2015.6.
Desikan, Rahul S.; Schork, Andrew J.; Wang, Yunpeng; Thompson, Wesley K.; Dehghan, Abbas & Ridker, Paul M. [Vis alle 47 forfattere av denne artikkelen] (2015). Polygenic overlap between C-reactive protein, plasma lipids, and Alzheimer disease. Circulation. ISSN 0009-7322. 131(23), s. 2061–2069. doi: 10.1161/CIRCULATIONAHA.115.015489. Fulltekst i vitenarkiv
Couey, Jonathan Jay; Witoelar, Aree Widya; Zhang, Sheng Jia; Zheng, Kang; Ye, Jing & Dunn, Benjamin Adric [Vis alle 11 forfattere av denne artikkelen] (2013). Recurrent inhibitory circuitry as a mechanism for grid formation. Nature Neuroscience. ISSN 1097-6256. 16(3), s. 318–324. doi: 10.1038/nn.3310.

Se alle arbeider i Cristin

Rongve, Arvid; Witoelar, Aree Widya; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla & Clarimon, Jordi [Vis alle 40 forfattere av denne artikkelen] (2019). Author Correction: GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study (Scientific Reports, (2019), 9, 1, (7013), 10.1038/s41598-019-43458-2). Scientific Reports. ISSN 2045-2322. 9(1). doi: 10.1038/s41598-019-51827-0.
Smeland, Olav Bjerkehagen; Wang, Yunpeng; Frei, Oleksandr; Li, Wen; Hibar, Derrek & Franke, Barbara [Vis alle 13 forfattere av denne artikkelen] (2017). Conditional false discovery rate analysis of genome-wide association studies uncovers genetic loci shared between schizophrenia and volumes of hippocampus, putamen and intracranial volume.
Smeland, Olav Bjerkehagen; Frei, Oleksandr; Wang, Yunpeng; Fan, Chun Chieh; Shadrin, Alexey A. & Li, Wen [Vis alle 13 forfattere av denne artikkelen] (2017). C-Reactive Protein Levels and Schizophrenia Share Genetic Influences.
Smeland, Olav Bjerkehagen; Frei, Oleksandr; Wang, Yunpeng; Fan, Chun Chieh; Alexey, Shadrin & Li, Wen [Vis alle 13 forfattere av denne artikkelen] (2017). Increased discovery of risk loci for bipolar disorder by leveraging prior probabilities of true associations using the covariate modulated mixture model (CM3).
Zuber, Verena; Marconett, Crystal; Shi, Jianxin; Hua, Xing; Wheeler, William & Yang, Chenchen [Vis alle 41 forfattere av denne artikkelen] (2016). Pleiotropic analysis of lung cancer and blood triglycerides. Journal of the National Cancer Institute. ISSN 0027-8874. 108:djv167(12), s. 1–4. doi: 10.1093/jnci/djw167.
Smeland, Olav Bjerkehagen; Kauppi, Karolina; Wang, Yunpeng; Frei, Oleksandr; Li, Wen & Hill, David W [Vis alle 17 forfattere av denne artikkelen] (2016). Schizophrenia and general cognitive function share genetic influences.
Smeland, Olav Bjerkehagen; Witoelar, Aree; Wang, Yunpeng; Chen, Chi-Hua; Djurovic, Srdjan & Dale, Anders [Vis alle 7 forfattere av denne artikkelen] (2016). Genetic overlap between schizophrenia and brain structural volumes indicates shared molecular genetic mechanisms with potential relevance for antipsychotics .
Smeland, Olav Bjerkehagen; Witoelar, Aree; Lo, Min-Tzu; Tesli, Martin Steen; Wang, Yunpeng & Hinds, David A. [Vis alle 11 forfattere av denne artikkelen] (2016). Genetic overlap between schizophrenia and the Big Five personality traits.
Mäki-Marttunen, Tuomo; Halnes, Geir; Devor, Anna; Witoelar, Aree; Bettella, Francesco & Djurovic, Srdjan [Vis alle 10 forfattere av denne artikkelen] (2015). Towards biophysical psychiatry: A modeling approach for studying effects of schizophrenia-linked gens on single-neuron excitability.
Mäki-Marttunen, Tuomo; Halnes, Geir; Devor, Anna; Witoelar, Aree; Bettella, Francesco & Djurovic, Srdjan [Vis alle 10 forfattere av denne artikkelen] (2015). Towards biophysical psychiatry: A modeling approach for studying effects of schizophrenia-linked genes on single-neuron excitability.
Smeland, Olav Bjerkehagen; Lo, Min-Tzu; Witoelar, Aree; Tesli, Martin; Hinds, David & Hu, Youna [Vis alle 12 forfattere av denne artikkelen] (2015). Genetic overlap between Schizophrenia and the Big Five personality traits.
Dunn, Benjamin Adric; Witoelar, Aree Widya; Couey, Jonathan Jay; Moser, May-Britt; Moser, Edvard Ingjald & Witter, Menno [Vis alle 7 forfattere av denne artikkelen] (2012). 3899. Grid Cells Emerge From A Competitive Network. FENS.
Dunn, Benjamin Adric; Witoelar, Aree Widya; Couey, Jonathan Jay; Bonnevie, Tora; Moser, May-Britt & Moser, Edvard Ingjald [Vis alle 8 forfattere av denne artikkelen] (2012). 702.08/DDD24 - An inhibitory network of grid cells. SFN Abstract Viewer/Itinerary Planner.
Couey, Jonathan Jay; Witoelar, Aree Widya; Zhang, Sheng Jia; Czajkowski, Rafal; Dunn, Benjamin Adric & Ye, Jing [Vis alle 10 forfattere av denne artikkelen] (2012). 702.06/DDD22 - Medial entorhinal cortex layer ii stellate cells are embedded within a recurrent inhibitory network. SFN Abstract Viewer/Itinerary Planner.
Witoelar, Aree Widya & Roudi, Yasser (2011). Neural network reconstruction using kinetic Ising models with memory. BMC Neuroscience. ISSN 1471-2202.