Jonathan Flint

A Short Biography:

Jonathan Flint trained in medicine and psychiatry in London and Oxford before moving to UCLA at the beginning of 2016 to become one of the leaders of UCLA's Depression Grand Challenge, a campus wide initiative to find the causes of depression and use that knowledge to develop new, effective, therapies

Work Titles
UCLA Professor, Psychiatry and Biobehavioral Sciences Member, Neuroscience GPB Home Area

Contact Information:

Email Address:

Research Interest:

How genes influence behavior

My laboratory is undertaking a series of studies to find out how genetic variants alter behavior, with a particular focus on anxiety and depresson. We do this through genetic engineering and genetic mapping studies in mice, and through the analysis of large cohorts of human subjects, working to identify the relevant genetic variants and the genes upon which they act, as a starting point to exploring how genes influence behavior.

Genes, circuits, behavior


1- Over the last 20 years many thousands of genetic loci that contribute to behavioral variation have been identified in mice and rats.  This is the first step towards discovering genes, which in turn are expected to provide new insights into the biology of behavior, and, when the behavior is related to psychiatric disease, to aid the development of new therapies. Yet remarkably few genes have been unequivocally identified as causal. This project applies resources and techniques my laboratory developed, in particular the use of outbred animals for high resolution mapping and catalogs of genetic variants, to deliver an efficient and robust method, the knockout-interaction test, to identity genes at loci contributing to behavioral variation, particularly anxiety and depression.


2- There is a remarkable gap in our knowledge in the relationship between genes and behavior. On one hand we know the position in the genomes of thousands of genetic variants that alter the risk of psychiatric disease, or alter human personality and behavior (including our sleeping and coffee preferences); on the other we have powerful tools to identify and activate neuronal circuits in mammalian brains - we know, and can see, that activity in those circuits results in behavior. But no one knows how genes affect circuit funtion. By taking advantage of the wide-ranging effects of genetic variation on neural circuits and behavior, we aim to test the effect of genetic variation on circuit mechanism and hence develop new theories as to how the brain controls behavior

3- Major depressive disorder is the commonest psychiatric disorder and is recognized as the leading cause of disability worldwide. Yet depression has not benefited from the genetic advances that have begun to transform our understanding of other conditions. We work with colleagues around the world to identify genetic variants that alter the risk of depression, using large cohorts of patients with recurrent depression. 

Detailed Biography:

Jonathan Flint has been a pioneer in the genetics of behaviour. He showed that behaviour, and psychiatric diseases are genetically tractable targets, and he has made key advances in identifying their molecular underpinnings, particularly with his work on structural variants.   His genome-wide analyses of behaviour in rodents, precursors to GWAS in humans, revealed the polygenic architecture of behavior, arising from the joint action of many loci of small effect, a key insight for the design and interpretation of genetic studies in psychiatry. 

His work has had clinical relevance: probes developed in his laboratory are now part of standard screening protocols for intellectual disability across the world; his work on determining the causal pathway from mutation to behavioural phenotype resulted in the discovery of an important and unexpected cause of a human genetic disorder (neuronal migration defects), again with benefits for patients and families. 

He developed and pioneered novel approaches in mouse genetics, championing the use of multi-parental lines and outbred mice. Together with the widely used sequence data of classical inbred strains, these ideas and resources have transformed complex trait analysis in rodents.  

His insistence on the importance of careful delineation of phenotypes in psychiatric genetics resulted in his successful genetic analysis of major depression, and has opened new avenues to understanding the origins of the world’s leading cause of disability. Such work is necessary to develop new ways of treating patients.


A selected list of publications:

Jonathan Flint, Ralph J. Greenspan, Kenneth S. Kendler   How genes influence behaviour, Oxford University Press, 2020; Second Edition: .
Cai Na, Revez Joana A, Adams Mark J, Andlauer Till F M, Breen Gerome, Byrne Enda M, Clarke Toni-Kim, Forstner Andreas J, Grabe Hans J, Hamilton Steven P, Levinson Douglas F, Lewis Cathryn M, Lewis Glyn, Martin Nicholas G, Milaneschi Yuri, Mors Ole, Müller-Myhsok Bertram, Penninx Brenda W J H, Perlis Roy H, Pistis Giorgio, Potash James B, Preisig Martin, Shi Jianxin, Smoller Jordan W, Streit Fabien, Tiemeier Henning, Uher Rudolf, Van der Auwera Sandra, Viktorin Alexander, Weissman Myrna M, Weissman Myrna M, Kendler Kenneth S, Flint Jonathan   Minimal phenotyping yields genome-wide association signals of low specificity for major depression Nature genetics, 2020; 52(4): 437-447.
Nicod Jérôme, Davies Robert W, Cai Na, Hassett Carl, Goodstadt Leo, Cosgrove Cormac, Yee Benjamin K, Lionikaite Vikte, McIntyre Rebecca E, Remme Carol Ann, Lodder Elisabeth M, Gregory Jennifer S, Hough Tertius, Joynson Russell, Phelps Hayley, Nell Barbara, Rowe Clare, Wood Joe, Walling Alison, Bopp Nasrin, Bhomra Amarjit, Hernandez-Pliego Polinka, Callebert Jacques, Aspden Richard M, Talbot Nick P, Robbins Peter A, Harrison Mark, Fray Martin, Launay Jean-Marie, Pinto Yigal M, Blizard David A, Bezzina Connie R, Adams David J, Franken Paul, Weaver Tom, Wells Sara, Brown Steve D M, Potter Paul K, Klenerman Paul, Lionikas Arimantas, Mott Richard, Flint Jonathan   Genome-wide association of multiple complex traits in outbred mice by ultra-low-coverage sequencing Nature genetics, 2016; 48(8): 912-8.
Davies Robert W, Flint Jonathan, Myers Simon, Mott Richard   Rapid genotype imputation from sequence without reference panels Nature genetics, 2016; 48(8): 965-9.
Flint Jonathan   Sparse whole-genome sequencing identifies two loci for major depressive disorder Nature, 2015; 523(7562): 588-91.
Cai Na, Chang Simon, Li Yihan, Li Qibin, Hu Jingchu, Liang Jieqin, Song Li, Kretzschmar Warren, Gan Xiangchao, Nicod Jerome, Rivera Margarita, Deng Hong, Du Bo, Li Keqing, Sang Wenhu, Gao Jingfang, Gao Shugui, Ha Baowei, Ho Hung-Yao, Hu Chunmei, Hu Jian, Hu Zhenfei, Huang Guoping, Jiang Guoqing, Jiang Tao, Jin Wei, Li Gongying, Li Kan, Li Yi, Li Yingrui, Li Youhui, Lin Yu-Ting, Liu Lanfen, Liu Tiebang, Liu Ying, Liu Yuan, Lu Yao, Lv Luxian, Meng Huaqing, Qian Puyi, Sang Hong, Shen Jianhua, Shi Jianguo, Sun Jing, Tao Ming, Wang Gang, Wang Guangbiao, Wang Jian, Wang Linmao, Wang Xueyi, Wang Xumei, Yang Huanming, Yang Lijun, Yin Ye, Zhang Jinbei, Zhang Kerang, Sun Ning, Zhang Wei, Zhang Xiuqing, Zhang Zhen, Zhong Hui, Breen Gerome, Wang Jun, Marchini Jonathan, Chen Yiping, Xu Qi, Xu Xun, Mott Richard, Huang Guo-Jen, Kendler Kenneth, Flint Jonathan   Molecular signatures of major depression Current biology : CB, 2015; 25(9): 1146-56.
Mott Richard, Yuan Wei, Kaisaki Pamela, Gan Xiangchao, Cleak James, Edwards Andrew, Baud Amelie, Flint Jonathan   The architecture of parent-of-origin effects in mice Cell, 2014; 156(1-2): 332-42.
Flint Jonathan, Baud Amelie, Hermsen Roel, Guryev Victor, Stridh Pernilla, Graham Delyth, McBride Martin W, Foroud Tatiana, Calderari Sophie, Diez Margarita, Ockinger Johan, Beyeen Amennai D, Gillett Alan, Abdelmagid Nada, Guerreiro-Cacais Andre Ortlieb, Jagodic Maja, Tuncel Jonatan, Norin Ulrika, Beattie Elisabeth, Huynh Ngan, Miller William H, Koller Daniel L, Alam Imranul, Falak Samreen, Osborne-Pellegrin Mary, Martinez-Membrives Esther, Canete Toni, Blazquez Gloria, Vicens-Costa Elia, Mont-Cardona Carme, Diaz-Moran Sira, Tobena Adolf, Hummel Oliver, Zelenika Diana, Saar Kathrin, Patone Giannino, Bauerfeind Anja, Bihoreau Marie-Therese, Heinig Matthias, Lee Young-Ae, Rintisch Carola, Schulz Herbert, Wheeler David A, Worley Kim C, Muzny Donna M, Gibbs Richard A, Lathrop Mark, Lansu Nico, Toonen Pim, Ruzius Frans Paul, de Bruijn Ewart, Hauser Heidi, Adams David J, Keane Thomas, Atanur Santosh S, Aitman Tim J, Flicek Paul, Malinauskas Tomas, Jones E Yvonne, Ekman Diana, Lopez-Aumatell Regina, Dominiczak Anna F, Johannesson Martina, Holmdahl Rikard, Olsson Tomas, Gauguier Dominique, Hubner Norbert, Fernandez-Teruel Alberto, Cuppen Edwin, Mott Richard, Flint Jonathan   Combined sequence-based and genetic mapping analysis of complex traits in outbred rats Nature genetics, 2013; 45(7): 767-75.
Keane Thomas M, Goodstadt Leo, Danecek Petr, White Michael A, Wong Kim, Yalcin Binnaz, Heger Andreas, Agam Avigail, Slater Guy, Goodson Martin, Furlotte Nicholas A, Eskin Eleazar, Nellåker Christoffer, Whitley Helen, Cleak James, Janowitz Deborah, Hernandez-Pliego Polinka, Edwards Andrew, Belgard T Grant, Oliver Peter L, McIntyre Rebecca E, Bhomra Amarjit, Nicod Jérôme, Gan Xiangchao, Yuan Wei, van der Weyden Louise, Steward Charles A, Bala Sendu, Stalker Jim, Mott Richard, Durbin Richard, Jackson Ian J, Czechanski Anne, Guerra-Assunção José Afonso, Donahue Leah Rae, Reinholdt Laura G, Payseur Bret A, Ponting Chris P, Birney Ewan, Flint Jonathan, Adams David J   Mouse genomic variation and its effect on phenotypes and gene regulation Nature, 2011; 477(7364): 289-94.
Yalcin Binnaz, Wong Kim, Agam Avigail, Goodson Martin, Keane Thomas M, Gan Xiangchao, Nellåker Christoffer, Goodstadt Leo, Nicod Jérôme, Bhomra Amarjit, Hernandez-Pliego Polinka, Whitley Helen, Cleak James, Dutton Rebekah, Janowitz Deborah, Mott Richard, Adams David J, Flint Jonathan   Sequence-based characterization of structural variation in the mouse genome Nature, 2011; 477(7364): 326-9.
Keays David A, Tian Guoling, Poirier Karine, Huang Guo-Jen, Siebold Christian, Cleak James, Oliver Peter L, Fray Martin, Harvey Robert J, Molnár Zoltán, Piñon Maria C, Dear Neil, Valdar William, Brown Steve D M, Davies Kay E, Rawlins J Nicholas P, Cowan Nicholas J, Nolan Patrick, Chelly Jamel, Flint Jonathan   Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans Cell, 2007; 128(1): 45-57.
Valdar William, Solberg Leah C, Gauguier Dominique, Burnett Stephanie, Klenerman Paul, Cookson William O, Taylor Martin S, Rawlins J Nicholas P, Mott Richard, Flint Jonathan   Genome-wide genetic association of complex traits in heterogeneous stock mice Nature genetics, 2006; 38(8): 879-87.
Yalcin Binnaz, Willis-Owen Saffron A G, Fullerton Jan, Meesaq Anjela, Deacon Robert M, Rawlins J Nicholas P, Copley Richard R, Morris Andrew P, Flint Jonathan, Mott Richard   Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice Nature genetics, 2004; 36(11): 1197-202.

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