Bio

Honors & Awards


  • Travel Award, European Sleep Research Society (2010)
  • Travel award, World Sleep Organization (2011)
  • Young Scientist Award, Gordon Research Conference Pineal Cell Biology (2012)
  • Sigrid Juselius Fellowship, Sigrid Juselius Foundation (2013)
  • Finnish Cultural Foundation Fellowship, Finnish Cultural Foundation (2014)

Boards, Advisory Committees, Professional Organizations


  • Faculty board member, University of Jyvaskyla, Finland (2004 - 2006)
  • Board member, Finnish Society for Cell Biology (2005 - 2006)
  • Board member, Helsinki Graduate School in Biotechnology and Molecular Biology student association (2007 - 2010)
  • Chair, Helsinki Graduate school in Biotechnology and Molecular Biology student association (2009 - 2010)
  • Board member, Stanford University Postdoctoral Association (2013 - 2015)
  • Member, American Association for Sleep Medicine (2013 - Present)
  • Member, Sleep Research Society (2013 - Present)

Professional Education


  • Doctor of Philosophy, University Of Helsinki (2012)
  • Master of Science, University Of Jyvaskyla (2007)

Stanford Advisors


Research & Scholarship

Current Research and Scholarly Interests


My research focuses on determining genetic variants that control psychiatric traits, especially normal sleep regulation and sleep disorders. My main interest is narcolepsy that is a severe autoimmune sleep disorder. I am using statistical genetic and high throughput sequencing methods to detect mechanisms that regulate the predisposition to narcolepsy and other psychiatric diseases.

Publications

Journal Articles


  • Genetic background of extreme violent behavior MOLECULAR PSYCHIATRY Tiihonen, J., Rautiainen, M., Ollila, H. M., Repo-Tiihonen, E., Virkkunen, M., PALOTIE, A., Pietilainen, O., Kristiansson, K., Joukamaa, M., Lauerma, H., Saarela, J., Tyni, S., VARTIAINEN, H., Paananen, J., Goldman, D., Paunio, T. 2015; 20 (6): 786-792

    Abstract

    In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5-10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

    View details for DOI 10.1038/mp.2014.130

    View details for Web of Science ID 000354890200018

    View details for PubMedID 25349169

  • HLA-DPB1 and HLA Class I Confer Risk of and Protection from Narcolepsy. American journal of human genetics Ollila, H. M., Ravel, J., Han, F., Faraco, J., Lin, L., Zheng, X., Plazzi, G., Dauvilliers, Y., Pizza, F., Hong, S., Jennum, P., Knudsen, S., Kornum, B. R., Dong, X. S., Yan, H., Hong, H., Coquillard, C., Mahlios, J., Jolanki, O., Einen, M., Lavault, S., Högl, B., Frauscher, B., Crowe, C., Partinen, M., Huang, Y. S., Bourgin, P., Vaarala, O., Désautels, A., Montplaisir, J., Mack, S. J., Mindrinos, M., Fernandez-Vina, M., Mignot, E. 2015; 96 (1): 136-146

    Abstract

    Type 1 narcolepsy, a disorder caused by a lack of hypocretin (orexin), is so strongly associated with human leukocyte antigen (HLA) class II HLA-DQA1(∗)01:02-DQB1(∗)06:02 (DQ0602) that very few non-DQ0602 cases have been reported. A known triggering factor for narcolepsy is pandemic 2009 influenza H1N1, suggesting autoimmunity triggered by upper-airway infections. Additional effects of other HLA-DQ alleles have been reported consistently across multiple ethnic groups. Using over 3,000 case and 10,000 control individuals of European and Chinese background, we examined the effects of other HLA loci. After careful matching of HLA-DR and HLA-DQ in case and control individuals, we found strong protective effects of HLA-DPA1(∗)01:03-DPB1(∗)04:02 (DP0402; odds ratio [OR] = 0.51 [0.38-0.67], p = 1.01 × 10(-6)) and HLA-DPA1(∗)01:03-DPB1(∗)04:01 (DP0401; OR = 0.61 [0.47-0.80], p = 2.07 × 10(-4)) and predisposing effects of HLA-DPB1(∗)05:01 in Asians (OR = 1.76 [1.34-2.31], p = 4.71 × 10(-05)). Similar effects were found by conditional analysis controlling for HLA-DR and HLA-DQ with DP0402 (OR = 0.45 [0.38-0.55] p = 8.99 × 10(-17)) and DP0501 (OR = 1.38 [1.18-1.61], p = 7.11 × 10(-5)). HLA-class-II-independent associations with HLA-A(∗)11:01 (OR = 1.32 [1.13-1.54], p = 4.92 × 10(-4)), HLA-B(∗)35:03 (OR = 1.96 [1.41-2.70], p = 5.14 × 10(-5)), and HLA-B(∗)51:01 (OR = 1.49 [1.25-1.78], p = 1.09 × 10(-5)) were also seen across ethnic groups in the HLA class I region. These effects might reflect modulation of autoimmunity or indirect effects of HLA class I and HLA-DP alleles on response to viral infections such as that of influenza.

    View details for DOI 10.1016/j.ajhg.2014.12.010

    View details for PubMedID 25574827

  • HLA-DQ Allele Competition in Narcolepsy: A Comment on Tafti et al. DQB1 locus alone explains most of the risk and protection in narcolepsy with cataplexy in Europe SLEEP Ollila, H. M., Fernandez-Vina, M., Mignot, E. 2015; 38 (1): 147-151

    Abstract

    Although HLA-DQB1*06:02 is the strongest predisposing genetic factor for narcolepsy, the effect of this gene must be considered alongside that of its polymorphic partner, DQA1. In this paper, we extend an analysis of the effect of HLA-DQB1 on narcolepsy risk published recently by Tafti et al.Imputing allelic variation at the level of HLA-DQA1, we show that this locus also has a considerable effect on disease susceptibility. Our data are also compatible with previous findings in multi-ethnic group data sets showing that allele competition effects within the DQ1 group determine the amount of DQ0602 (the DQA1*01:02/DQB1*06:02 heterodimer), and consequently, the risk of developing narcolepsy. We also found an independent predisposing effect of DQB1*03:01 via a currently unknown mechanism.Both DQA1 and DQB1 influence narcolepsy risk.

    View details for DOI 10.5665/sleep.4342

    View details for Web of Science ID 000347169300017

    View details for PubMedID 25325462

  • Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample. PloS one Ramsay, H., Barnett, J. H., Miettunen, J., Mukkala, S., Mäki, P., Liuhanen, J., Murray, G. K., Jarvelin, M., Ollila, H., Paunio, T., Veijola, J. 2015; 10 (6)

    Abstract

    There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.

    View details for DOI 10.1371/journal.pone.0127602

    View details for PubMedID 26114663

  • Genome-wide association study of sleep duration in the Finnish population JOURNAL OF SLEEP RESEARCH Ollila, H. M., Kettunen, J., Pietilainen, O., Aho, V., Silander, K., Kronholm, E., Perola, M., Lahti, J., Raikkonen, K., Widen, E., Palotie, A., Eriksson, J. G., Partonen, T., Kaprio, J., Salomaa, V., Raitakari, O., Lehtimaki, T., Sallinen, M., Harma, M., Porkka-Heiskanen, T., Paunio, T. 2014; 23 (6): 609-618

    Abstract

    Sleep duration is genetically regulated, but the genetic variants are largely unknown. We aimed to identify such genes using a genome-wide association study (GWAS) combined with RNA expression at the population level, and with experimental verification. A GWAS was performed in a Finnish sample (n = 1941), and variants with suggestive association (P < 5 × 10(-5) ) were tested in a follow-up sample from the same population with sleep duration (n = 6834) and time in bed (n = 1720). Variants with pointwise association of P < 0.05 in the follow-up sample were analysed further. First, we correlated genotypes with transcript expression levels with sleep duration (n = 207). The expression levels of significant transcripts were further studied in experimental sleep restriction. Of the 31 variants with P < 5 × 10(-5) in the discovery sample, three variants showed nominal allelic association (P < 0.05) in the follow-up sample: rs10914351, near PTPRU (P = 0.049), rs1037079 in PCDH7-CENTD1 (P = 0.011) and rs2031573 near KLF6 (P = 0.044). The risk alleles for shorter sleep (rs2031573 and rs1037079) were also associated with higher KLF6 and PCDH7 expression levels (P < 0.05). Experimental sleep restriction increased the expression of KLF6 (P < 0.01). These data suggest that rs2031573 near KLF6 or related loci and rs1037079 between PCDH7-CENTD1 or related loci may contribute to the regulation of sleep duration via gene expression. These results illustrate the utility of combining different analytical approaches to identify genetic determinants for traits related to sleep physiology. However, additional studies are needed in order to understand the roles of KLF6 and PCDH7 in sleep regulation.

    View details for DOI 10.1111/jsr.12175

    View details for Web of Science ID 000345590700002

    View details for PubMedID 25109461

  • HLA DQB1*06:02 Negative Narcolepsy with Hypocretin/Orexin Deficiency SLEEP Han, F., Lin, L., Schormair, B., Pizza, F., Plazzi, G., Ollila, H. M., Nevsimalova, S., Jennum, P., Knudsen, S., Winkelmann, J., Coquillard, C., Babrzadeh, F., Strom, T. M., Wang, C., Mindrinos, M., Vina, M. F., Mignot, E. 2014; 37 (10): 1601-1608

    View details for DOI 10.5665/sleep.4066

    View details for Web of Science ID 000343147400006

  • Dual Cases of Type 1 Narcolepsy with Schizophrenia and Other Psychotic Disorders JOURNAL OF CLINICAL SLEEP MEDICINE Canellas, F., Lin, L., Rosa Julia, M., Clemente, A., Vives-Bauza, C., Ollila, H. M., Hong, S. C., Arboleya, S. M., Einen, M. A., Faraco, J., Fernandez-Vina, M., Mignot, E. 2014; 10 (9): 1011-1018

    Abstract

    Cases of narcolepsy in association with psychotic features have been reported but never fully characterized. These patients present diagnostic and treatment challenges and may shed new light on immune associations in schizophrenia.Our case series was gathered at two narcolepsy specialty centers over a 9-year period. A questionnaire was created to improve diagnosis of schizophrenia or another psychotic disorder in patients with narcolepsy. Pathophysiological investigations included full HLA Class I and II typing, testing for known systemic and intracellular/synaptic neuronal antibodies, recently described neuronal surface antibodies, and immunocytochemistry on brain sections to detect new antigens.Ten cases were identified, one with schizoaffective disorder, one with delusional disorder, two with schizophreniform disorder, and 6 with schizophrenia. In all cases, narcolepsy manifested first in childhood or adolescence, followed by psychotic symptoms after a variable interval. These patients had auditory hallucinations, which was the most differentiating clinical feature in comparison to narcolepsy patients without psychosis. Narcolepsy therapy may have played a role in triggering psychotic symptoms but these did not reverse with changes in narcolepsy medications. Response to antipsychotic treatment was variable. Pathophysiological studies did not reveal any known autoantibodies or unusual brain immunostaining pattern. No strong HLA association outside of HLA DQB1*06:02 was found, although increased DRB3*03 and DPA1*02:01 was notable.Narcolepsy can occur in association with schizophrenia, with significant diagnostic and therapeutic challenges. Dual cases maybe under diagnosed, as onset is unusually early, often in childhood. Narcolepsy and psychosis may share an autoimmune pathology; thus, further investigations in larger samples are warranted.

    View details for DOI 10.5664/jcsm.4040

    View details for Web of Science ID 000341999700012

    View details for PubMedID 25142772

  • Genome wide analysis of narcolepsy in China implicates novel immune loci and reveals changes in association prior to versus after the 2009 H1N1 influenza pandemic. PLoS genetics Han, F., Faraco, J., Dong, X. S., Ollila, H. M., Lin, L., Li, J., An, P., Wang, S., Jiang, K. W., Gao, Z. C., Zhao, L., Yan, H., Liu, Y. N., Li, Q. H., Zhang, X. Z., Hu, Y., Wang, J. Y., Lu, Y. H., Lu, C. J., Zhou, W., Hallmayer, J., Huang, Y. S., Strohl, K. P., Pollmächer, T., Mignot, E. 2013; 9 (10)

    Abstract

    Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7 × 10(-9) OR 0.77), ZNF365 (rs10995245 max P = 1.2 × 10(-11) OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2 × 10(-9) OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10(-9) beta -1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8 × 10(-10) OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases.

    View details for DOI 10.1371/journal.pgen.1003880

    View details for PubMedID 24204295

  • Genome-wide scan of job-related exhaustion with three replication studies implicate a susceptibility variant at the UST gene locus HUMAN MOLECULAR GENETICS Sulkava, S., Ollila, H. M., Ahola, K., Partonen, T., Viitasalo, K., Kettunen, J., Lappalainen, M., Kivimaki, M., Vahtera, J., Lindstrom, J., Harma, M., Puttonen, S., Salomaa, V., Paunio, T. 2013; 22 (16): 3363-3372

    Abstract

    Job-related exhaustion is the core dimension of burnout, a work-related stress syndrome that has several negative health consequences. In this study, we explored the molecular genetic background of job-related exhaustion. A genome-wide analysis of job-related exhaustion was performed in the GENMETS subcohort (n = 1256) of the Finnish population-based Health 2000 study. Replication analyses included an analysis of the strongest associations in the rest of the Health 2000 sample (n = 1660 workers) and in three independent populations (the FINRISK population cohort, n = 10 753; two occupational cohorts, total n = 1451). Job-related exhaustion was ascertained using a standard self-administered questionnaire (the Maslach Burnout Inventory (MBI)-GS exhaustion scale in the Health 2000 sample and the occupational cohorts) or a single question (FINRISK). A variant located in an intron of UST, uronyl-2-sulfotransferase (rs13219957), gave the strongest statistical evidence in the initial genome-wide study (P = 1.55 × 10(-7)), and was associated with job-related exhaustion in all the replication sets (P < 0.05; P = 6.75 × 10(-7) from the meta-analysis). Consistent with studies of mood disorders, individual common genetic variants did not have any strong effect on job-related exhaustion. However, the nominally significant signals from the allelic variant of UST in four separate samples suggest that this variant might be a weak risk factor for job-related exhaustion. Together with the previously reported associations of other dermatan/chondroitin sulfate genes with mood disorders, these results indicate a potential molecular pathway for stress-related traits and mark a candidate region for further studies of job-related and general exhaustion.

    View details for DOI 10.1093/hmg/ddt185

    View details for Web of Science ID 000322341300016

    View details for PubMedID 23620144

  • Nightmares: Prevalence among the Finnish General Adult Population and War Veterans during 1972-2007. Sleep Sandman, N., Valli, K., Kronholm, E., Ollila, H. M., Revonsuo, A., Laatikainen, T., Paunio, T. 2013; 36 (7): 1041-1050

    Abstract

    To investigate the prevalence of nightmares among the Finnish general adult population during 1972-2007 and the association between nightmare prevalence and symptoms of insomnia, depression, and anxiety in World War II veterans.Eight independent cross-sectional population surveys of the National FINRISK Study conducted in Finland in 1972, 1977, 1982, 1987, 1992, 1997, 2002, and 2007.Epidemiologic.A total of 69,813 people (33,811 men and 36,002 women) age 25-74 years.N/A.The investigation of nightmare prevalence and insomnia, depression, and anxiety symptoms was based on questionnaires completed by the participants. Among the whole sample, 3.5% of the men and 4.8% of the women reported frequent nightmares (P < 0.0001 for sex difference), but the prevalence was affected by the age of participants and the year of the survey. Nightmare prevalence increased with age, particularly among the men. The number of people reporting occasional nightmares increased roughly by 20% for both sexes from 1972 to 2007 (P < 0.0001). Participants with war experiences reported more frequent nightmares and symptoms of insomnia, depression, and anxiety than participants without such experiences (P < 0.0001).Prevalence of nightmares was affected by the sex and age of the participants, and occasional nightmares have become more common in Finland. Exposure to war elevates nightmare prevalence as well as insomnia, depression, and anxiety symptoms even decades after the war; large numbers of war veterans can affect nightmare prevalence on population level.Sandman N; Valli K; Kronholm E; Ollila HM; Revonsuo A; Laatikainen T; Paunio T. Nightmares: prevalence among the Finnish general adult population and war veterans during 1972-2007. SLEEP 2013;36(7):1041-1050.

    View details for DOI 10.5665/sleep.2806

    View details for PubMedID 23814341

  • TRIB1 constitutes a molecular link between regulation of sleep and lipid metabolism in humans TRANSLATIONAL PSYCHIATRY Ollila, H. M., Utge, S., Kronholm, E., Aho, V., van Leeuwen, W., Silander, K., Partonen, T., Perola, M., Kaprio, J., Salomaa, V., Sallinen, M., Harma, M., Porkka-Heiskanen, T., Paunio, T. 2012; 2

    Abstract

    Epidemiological studies show association between sleep duration and lipid metabolism. In addition, inactivation of circadian genes induces insulin resistance and hyperlipidemia. We hypothesized that sleep length and lipid metabolism are partially controlled by the same genes. We studied the association of total sleep time (TST) with 60 genetic variants that had previously been associated with lipids. The analyses were performed in a Finnish population-based sample (N = 6334) and replicated in 2189 twins. Finally, RNA expression from mononuclear leucocytes was measured in 10 healthy volunteers before and after sleep restriction. The genetic analysis identified two variants near TRIB1 gene that independently contributed to both blood lipid levels and to TST (rs17321515, P = 8.92(*)10(-5), Bonferroni corrected P = 0.0053, β = 0.081 h per allele; rs2954029, P = 0.00025, corrected P = 0.015, β = 0.076; P<0.001 for both variants after adjusting for blood lipid levels or body mass index). The finding was replicated in the twin sample (rs17321515, P = 0.022, β = 0.063; meta-analysis of both samples P = 8.1(*)10(-6), β = 0.073). After the experimentally induced sleep restriction period TRIB1 expression increased 1.6-fold and decreased in recovery phase (P = 0.006). In addition, a negative correlation between TRIB1 expression and slow wave sleep was observed in recovery from sleep restriction. These results show that allelic variants of TRIB1 are independently involved in regulation of lipid metabolism and sleep. The findings give evidence for the pleiotropic nature of TRIB1 and may reflect the shared roots of sleep and metabolism. The shared genetic background may at least partially explain the mechanism behind the well-established connection between diseases with disrupted metabolism and sleep.

    View details for DOI 10.1038/tp.2012.20

    View details for Web of Science ID 000315990800013

    View details for PubMedID 22832862

  • Replication of GWAS of bipolar disorder: association of SNPs near CDH7 with bipolar disorder and visual processing MOLECULAR PSYCHIATRY Soronen, P., Ollila, H. M., Antila, M., Silander, K., Palo, O. M., Kieseppa, T., Lonnqvist, J., Peltonen, L., Tuulio-Henriksson, A., Partonen, T., Paunio, T. 2010; 15 (1): 4-6

    View details for DOI 10.1038/mp.2009.86

    View details for Web of Science ID 000272992600003

    View details for PubMedID 20029406

  • Findings from bipolar disorder genome-wide association studies replicate in a Finnish bipolar family-cohort MOLECULAR PSYCHIATRY Ollila, H. M., Soronen, P., Silander, K., Palo, O. M., Kieseppa, T., Kaunisto, M. A., Lonnqvist, J., Peltonen, L., Partonen, T., Paunio, T. 2009; 14 (4): 351-353

    View details for DOI 10.1038/mp.2008.122

    View details for Web of Science ID 000264426000003

    View details for PubMedID 19308021

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