Lu Yi

About me

I am a Principal Researcher at Karolinska Institutet (KI), Sweden. I lead a research group conducting psychiatric genetics research, especially in major depressive disorder (MDD). I am co-directing the KI Psychiatric Genomics Institute and the Nordic Tryggve consortium with Professor Patrick Sullivan. 

My research involves integrating large-scale genomic data and nationwide electronic healthcare records to investigate depression subtypes, as a way to reduce the substantial heterogeneity in this disorder. My long-term research vision is to promote targeted drug development and treatment optimization for MDD patient subgroups to achieve precision psychiatry. 

My research excellence has been recognised nationally and internationally, for which I have been awarded many prestigious grants including a recent award of €1.5 million from European Research Council (ERC). I am also the Sweden PI on major funding from US-NIMH and EU-Horizon2020.

Research description

1.         Genetics of major depressive disorder and its subtypes

MDD is heterogeneous; however, the extent to which genetic factors distinguish patient subgroups (genetic heterogeneity) remains uncertain. We therefore seek evidence for genetic heterogeneity in MDD by studying patient subgroups. In particular, we focus on patients who are most severely ill ("extreme MDD"). I am also a key analyst in the Psychiatric Genomics Consortium MDD working group. 

Selected publications:

1. Harder A, Nguyen TD, Pasman J, Mosing MA, Hägg S, Lu Y. Genetics of age-at-onset in major depression. Translational Psychiatry 2022 12;1 124-. PMID: 35347114.
2. Nguyen TD, Harder A, Xiong Y, Kowalec K, Hägg S, Cai N, Kuja-Halkola R, Dalman C, Sullivan PF, Lu Y. (2022) Genetic heterogeneity and subtypes of major depression. Molecular Psychiatry, Epub 08 January 2022. PMID: 34997191.
3. Kendall KM, Van Assche E, Andlauer TFM, Choi KW, Luykx JJ, Schulte EC, Lu Y. (2021) The genetic basis of major depression. Psychological medicine 2021; 1-14. PMID: 33682643.
4. Clements CC, Karlsson R, Lu Y, Jureus A, Ruck C, Andersson E, Boberg J, Pedersen NL, Bulik CM, Nordenskjold A, Palsson E, Sullivan PF, Landen M. (2021) Genome-wide association study of patients with a severe major depressive episode treated with electroconvulsive therapy. Molecular Psychiatry, 2021. PMID: 33483693.

2.         Trans-Nordic collaboration of “register genomics” in psychiatry

I have co-led the Nordic Tryggve consortium since 2018 (Tryggve: trans-Nordic collaboration on register and genomics research in psychiatry). The Tryggve consortium has enabled integration of genetics in population-based psychiatric studies in Sweden, Denmark, and Norway. We have achieved comprehensive harmonization of software, data processing pipelines, and register phenotype and genomic data using singularity containers. Altogether, these allow us to analyze Nordic register and genomic data in a unified scheme where we ask empirical questions and get rapid, secure, and reproducible answers.

Selected publications:

1. Song J, Yao S, Kowalec K, Lu Y, Sariaslan A, Szatkiewicz JP, Larsson H, Lichtenstein P, Hultman C, Sullivan PF. The impact of common and rare genetic variation on cognition and schizophrenia. Molecular Psychiatry (in press).
2. Kowalec K, Lu Y, Song J, Dalman C, Hultman C, Larsson H, Lichtenstein P, Sullivan PF. (2021) The association between family history and genomic burden with schizophrenia mortality: a Swedish population-based register and genetic sample study. Translational Psychiatry, 2021 Mar 15;11(1):163. PMID: 33723211.
3. Kowalec K, Lu Y, Sariaslan A, Song J, Ploner A, Dalman C, Hultman C, Larsson H, Lichtenstein P, Sullivan PF. (2019) Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia: A Swedish National register and genomic study. Molecular Psychiatry, Epub 12 November 2019. PMID: 31712719.
4. Lu Y, Pouget JG, Andreassen OA, Djurovic S, Esko T, Hultman CM, Metspalu A, Milani L, Werge T, Sullivan PF. (2017) Genetic risk scores and family history as predictors of schizophrenia in Nordic registers. Psychological medicine 2017; 1-9 PMID: 28942743.

3.         Genetic risk factors of other complex disorders

I led and contributed to many genome-wide association studies on complex traits and diseases of medical importance, including cancers, eye diseases, and allergic diseases. These work have been published in leading genetic journals, including three in Nature Genetics.

Selected publications:

1. Ferreira MA, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD, Helmer Q, Tillander A, Ullemar V, van Dongen J, Lu Y#, Rüschendorf F, et al. (2017) Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nat Genet 2017 49; 1752–1757. [# Joint first author] PMID: 29083406.
2. Lu Y,  Ek WE,  Whiteman D,  Vaughan TL,  Spurdle AB,  Easton DF,  Pharoah PD,  Thompson DJ,  Dunning AM,  Hayward NK,  Chenevix-Trench G,  Macgregor S,  BEACON Consortium,  Q-MEGA and AMFS Investigators,  ANECS-SEARCH,  UKOPS-SEARCH. Most common 'sporadic' cancers have a significant germline genetic component. Human molecular genetics 2014 23;22 6112-8. PMID: 24943595.
3. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, Edwards SL, Pickett HA, Shen HC, Smart CE, Hillman KM, Mai PL, Lawrenson K, Stutz MD, Lu Y, et al. (2013) Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nature genetics 2013 45;4 371-84. PMID: 23535731.
4. Lu Y, Vitart V, Burdon KP, Khor CC, Bykhovskaya Y, Mirshahi A, Hewitt AW, Koehn D, Hysi PG, Ramdas WD, et al. (2013) Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nature genetics 2013 45;2 155-63. PMID: 23291589.

Teaching portfolio

Supervision

Postdoc Joelle Pasman. 

Research specialist Tong Gong. 

PhD student Thi Thuy Dung Nguyen. “Aetiology and outcomes in psychiatric disorders”, since 2019.11. As main supervisor. 

PhD student Ying Xiong. "Genetic epidemiology of treatment-resistant depression", since 2021. As main supervisor. 

PhD student Arvid Harder. "Genomics and treatment outcomes of major depressive disorder subtypes", since 2023. As main supervisor. 

PhD student Jet Termorshuizen. “Genetic and environmental factors influencing the course and outcome of eating disorder”, since 2020.01. As co-supervisor. 

Former students

PhD student Ashley Thompson. “Prediction of negative life outcomes in children with ADHD”. As co-supervisor. (Defended thesis 2022.02.18)

Bachelor student Alison Baxley, Bachelor Thesis in Medical Science with a Major in Biomedicine, Karolinska Institutet. “Polygenic risk scores for schizophrenia and childhood accidents, injury and self-harm”. Spring 2017.

Teaching

Lecturer: "Psychiatric Genetics" within the Research School of Psychiatry (Forskarskolan inom klinisk psykiatri), Karolinska Institutet and Region Stockholm. Feb 6-10, 2023.

Course: “Molecular genetic psychiatry”. Clinical Psychology program, Karolinska Institutet. 2017, 2018, 2019.

Course: “Molecular epidemiology”. Epidemiology program, Karolinska Institutet. 2018, 2020.

Summer school: “GWAS and imputation”, Brain Imaging Genetics Summer School, Nijmegen, the Netherlands. 2018.

 

Education

PhD: Genetic Association Studies of Complex Traits. 2013. School of Mathematics and Physics, The University of Queensland; Statistical Genetics, QIMR Berghofer Medical Research Institute, Australia

Master, major of Statistics. Uppsala University and Högskolan Dalarna, Sweden

Academic honours, awards and prizes

My research are proudly supported by

European Research Council Starting Grant 2021, PI. 2022-2027.

KI Faculty-funded career position as Senior Researcher. 2022-2024.

Swedish Research Council. PI. 2022-2026.

European Union's Horizon 2020. Grant No 964874. Sub-award PI. 2021-2025.

NIH/NIMH R01 MH123724. Co-PI/Sub-award PI. 2020-2025.

KI Faculty-funded career position as Assistant Professor. 2018-2022.

StratNeuro Start Up Award, KI Neuroscience, 2019-2020. 

2018 NARSAD Young Investigator Award, Brain & Behavior Research Foundation, USA. 2019-2021.

KI Research Foundation. 2018-2019.

Assistant professor, funded by the Department of Medical Epidemiology and Biostatistics (rank #1). 2018-2022

NHMRC Early Career Fellowship (CJ Martin - Overseas Biomedical Fellowship). Australian Government. 2015-2018

Australian delegate of early career researcher at the 64th Nobel Laureates Meeting (Physiology or Medicine). Australian Academy of Science. 2014