• About Genetics Research at QCMHR

• Genetics Projects

• Genetics Publications

Funding

Our research program is supported by funding from:

Queensland Health

Ipswich Hospital Foundation

Australian National Health and Medical Research Foundation

US National Institute of Mental Health

Stanley Medical Research Institute

Rebecca L Cooper Medical Research Foundation

Staff

Director - Prof Bryan Mowry For Biography Click Here

Laboratory Staff

Herlina Handoko
Heather Smith
Cheryl Filippich
Nick Matigian

Clinical Staff

Brisbane
Deborah Nertney
Alex Zerbe
Michelle Coleman
Anna Rybak
Lynda Glasgow
Maria Sutherland
Duncan McLean
Joanne King
Jessica Lorenzo
Lesley Jones

Melbourne
Carlyn Muir
Lauren Hoiles
Gayle Franklin

PhD students
Amanda Jones
Elizabeth Holliday

About Our Work

There is good evidence from family studies that genes play an important causative role in the development of schizophrenia. The role has been confirmed in twin and adoption studies, but the pattern of inheritance is complex. Available data suggest multiple genes, each exerting small to moderate effect on overall disease risk, interacting with environmental factors in a neurodevelopmental context to confer vulnerability. Potential environmental factors include: retroviral (RNA) elements discovered in patients' cerebro-spinal fluid and expressed in frontal brain cortex samples; higher risk reported with urban versus rural birth; and perinatal factors.

The molecular genetic revolution has greatly accelerated the ability to search for disease genes. Prior to the mid 1970's, the only markers available for mapping diseases were blood groups, serum proteins and HLA tissue types relating to only a handful of chromosomal locations. With the discovery of certain enzyme's ability to cut DNA by recognizing specific sequences of 4-6 base pairs in length, restriction fragment length polymorphisms (RFLPs) were created for use as genome-wide markers for mapping disease genes. Polymerase chain reaction (PCR) methodology made it possible to amplify genome-wide, highly polymorphic microsatellite markers (STRPs), superseding RFLPs. Single nucleotide polymorphisms (SNPs) involving a single base change, are now also being utilized because they are easily detected, adaptable to high throughput, automated typing, and they are abundant, occurring one in every 1000 base pairs, based on results of the Human Genome Project and Celera Genomics.

Our work is aimed at identifying susceptibility genes for schizophrenia and related disorders. We are studying both ethnically diverse (heterogeneous) and genetically isolated (homogeneous) populations, to account for two different possibilities: (1) that the same, frequently occurring causative genes occur in all populations and (2) that rare genes may exist in one or more genetically homogeneous populations. We also pay attention to refining the phenotype while applying the latest molecular genetic and analytic techniques to large multicentre studies and to population isolates.

Research Program

Past Projects

Molecular genetics of schizophrenia in a US/Australian case/control cohort

This study was funded by the NHMRC and conducted between 1991 and 1999.  Over 1000 families were screened for possible inclusion based on family history of disease. From this screening sample, 45 Australian families with multiple affected members were included. A genome screen on the first 43 pedigrees (the first 18 Australian, plus 25 US pedigrees), using a map of over 300 genetic markers, was conducted in 1996. Regions on chromosomes 2q, 4q, 9q, 10q and 11q provided nominal evidence that they may contain factors associated with inheritance of vulnerability to schizophrenia. Follow up fine mapping supported the initial findings for schizophrenia susceptibility regions on chromosomes 2 and 10. 

Molecular genetics of schizophrenia in a US/Australian sib-pair cohort

Funded by the NIMH, a collaboration of nine centres (QCMHR and eight US sites) was established to recruit 500 independent affected sib pairs (ASPs) with schizophrenia to carry out molecular and linkage analyses.

By the completion of the study in 2003, we had recruited eighty five ASPs from within Australia . A total of 535 ASPs were recruited from the entire collaboration. Outcomes of this study will be published in mid-2005.

Molecular genetics of psychosis in Fiji

Indigenous Fijians and Fijian Indians (originally imported as indentured labourers from India 80 to 120 years ago) represent two distinct populations. We have collected a sample of Indigenous Fijian (partially genetically isolated) and Indian Fijian subjects with psychotic disorders for future gene mapping studies using linkage disequilibrium analysis.  Approximately 600 subjects (probands plus available parents and siblings) were recruited from St Giles Hospital, Suva , and diagnostically ascertained. Another 100 (50 from each population) non-psychotic control subjects were recruited to determine allele frequencies for gene studies. 

Although recruitment for the above studies is complete, data will be included in future candidate gene studies in our own lab and together with collaborating labs.

Ongoing Projects

Molecular genetics of schizophrenia in a US/Australian case/control cohort

QCMHR is one of ten collaborating sites which together has received an additional four years of funding from the NIMH to recruit a large cohort of individuals with a diagnosis of schizophrenia, plus matched controls without psychosis. The Australian recruitment target is 1000 affected individuals over three years. When complete, this will be the largest sample ever recruited for genetics studies in schizophrenia.

Based on these data, extensive genetic analyses will be carried out to refine the search for schizophrenia susceptibility genes. We will select positive regions in our genome scan of the ASP sample, and then develop single nucleotide polymorphism (SNP) maps across these regions using information from public databases and from our own SNP discovery. Analyses will be used to evaluate evidence for genetic association, and identify candidate genes to be studied. Subsidiary analyses will be carried out on subsets of families identified based on the distribution of critical variables such as age of onset and typical quality of symptoms.

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Download Documentation

Molecular Genetics Information Sheet (.pdf)

Molecular Genetics Brochure (.pdf)

This study is in its second year of operation.

Australian twin pairs study

Adoption and twin studies have been crucial for establishing the genetic basis for psychotic disorders, both schizophrenia and bipolar disorder. Funded by the Stanley Foundation (USA) and the NHMRC, this project aims to collect a sample of about 80 twins, male and female, monozygotic and dizygotic, each of whom has at least one member with a psychotic disorder. A sample of about 45 control twins where both members are unaffected will also be collected. We aim to investigate the role of genetic and non-genetic risk factors, and behavioural markers reportedly associated with psychotic disorders. The study will include a series of neurocognitive and neurophysiological assessments and Magnetic Resonance Imaging (MRI) scans, with the goal of clarifying the psychotic phenotype(s) for genetic analyses.

Download Documentation.

Twin Pairs Study Information sheet (.pdf)

Twin Pairs Study Brochure (.pdf)

This study is in its third year of operation.

Molecular genetics of schizophrenia in the Iban of Sarawak

The Iban are indigenous people of Malaysia who have remained genetically distinct through geography and limited contact by outsiders. The aims of this study are to identify extended families containing more than one individual with schizophrenia; then to confirm these diagnoses by standardised research interviews, to gather systematic data on relatives affected by schizophrenia, and to take blood samples from these individuals and relevant family members.  The long-range goal is to identify a major gene that contributes to a vulnerability to schizophrenia in this restricted gene-pool.

In the first phase of this study, analysis of medical record data indicated that treated rates of schizophrenia among the Iban were higher than the reported prevalence for many populations at risk, including many small-scale societies, although different methodological approaches may partly explain these findings. Given the cultural patterns of treatment seeking behaviour, treated rates of schizophrenia reported here may closely approximate the population prevalence of this disorder. These results, together with previous fieldwork documenting extended pedigrees, have provided the epidemiological basis for the molecular genetic phase of our study, which is currently under way.

Now in its 4 th year, recruitment is still ongoing for this study and is expected to be complete by 2005.

Genetic study of schizophrenia in various caste populations of Tamil Nadu, India

The Brahmin people of Tamil Nadu are a partially isolated group who, like the Iban, seem an important population to sample for genetic studies. One hundred and six Affected Sibling Pair (ASP) families and 121 complete trios were recruited by 2004. Since then 50 male individuals from each of four castes have been recruited for genetic evolutionary studies, and for allele frequency determination for our schizophrenia genome-wide and fine-mapping studies. Recruitment is ongoing with a recruitment target of 400 ASP families and 400 trios.

PUBLICATIONS

•  MOWRY, B.J., and Lennon, D.P. (1998). Puerperal psychosis: Associated clinical features in a psychiatric hospital mother-baby unit. Australian and New Zealand Journal of Psychiatry, 32(2):287-290.

•  Daniels, B.A., Kirkby, K.C., Hay, D.A., MOWRY, B.J., Jones, I.H. (1998). Predictability of rehospitalisation over five years for schizophrenia, bipolar disorder and depression. Australian and New Zealand Journal of Psychiatry, 32(2):281-286.

•  Schizophrenia Collaborative Linkage Group for Chromosome 22. (1998). A transmission disequilibrium and linkage analysis of D22S278 marker alleles in 574 families: further support for a susceptibility locus for schizophrenia at 22q12. Schizophrenia Research, 32(2):115-121.

•  Levinson, D.F., Mahtani, M.M., Nancarrow, D.J., Brown, D.M., Kruglyak, L., Kirby, A., Hayward, N.K., Crowe, R.R., Andreasen, N.C., Silverman, J.M., Endicott, J., Sharpe, L., Mohs, R.C., Siever, L.J., Walters, M.K., Lennon, D.P., Jones, H.J., Nertney, D.A., Daly, M.J. and MOWRY, B.J. (1998). Genome scan of schizophrenia. American Journal of Psychiatry, 155:741-750.

•  Kirkby, K.C., Hay, D.A., Daniels, B.A., Jones, I.H., MOWRY, B.J. (1998). Comparison between register and structured interview diagnoses of schizophrenia: a case for longitudinal diagnostic profiles. Australian and New Zealand Journal of Psychiatry, 32:410-414.

•  Martinez, M., Goldin, L.R., Cao, Q., Zhang, J., Sanders, A.R., Nancarrow, D.J., Taylor, J., Levinson, D.F., Kirby, A., Crowe, R.R., Andreasen, N.C., Black, D.W., Silverman, J.M., Lennon, D.P., Nertney, D.A., Brown, D.M., MOWRY, B.J., Gershon, E.S., and Gejman, P.V. (1999). A follow-up study on a susceptibility locus for schizophrenia on chromosome 6q. American Journal of Medical Genetics. (Neuropsychiatric Genet.) 88:337-343.

•  Levinson, D.F., and MOWRY, B.J. Genetics of Schizophrenia. Genetic influences on neural and behavioural functions. Pfaff, Donald W., Berrettini, Wade H., Maxson, Stephen C., and Joh, Tong H., eds., CRC Press, New York, 2000. pp. 47-82.

•  Nancarrow, D.J., Levinson, D.F., Taylor, J.M., Hayward, N.K., Walters, M.K., Lennon, D.P., Nertney, D.A., Mahtani, M.M., Brown, D.M., Kirby, A., Kruglyak, L., Crowe, R.R., Andreasen , N.C. , Black, D.W., Silverman, J.M., Mohs, R.C., Siever, L.J., Endicott, J., Sharpe, L. and MOWRY, B.J. (2000). No support for linkage to the bipolar regions on chromosomes 4p, 18p or 18q in 43 schizophrenia pedigrees. American Journal of Medical Genetics. (Neuropsychiatric Genetics) 96:224-227.

•  Daniels, B.A., Kirkby, K.C., Mitchell, P., Hay D., and MOWRY, B. (2000). Seasonal variation in hospital admission for bipolar disorder, depression and schizophrenia. Acta Psychiatrica Scandinavica, 102:38-43.

•  Levinson, D.F., Holmans, P., Straub, R.E., Owen, M.J., Wildenauer, D.B., Gejman, P.V., Pulver, A.E., Laurent, C., Kendler, K.S., Walsh, D., Norton, N., Williams, N.M., Schwab, S.G., Lerer, B., MOWRY, B.J., Sanders, A.R., Antonarakis, S.E., Blouin, J.L., DeLeuze, J.F., and Mallet, J. (2000). Multicenter Linkage Study of Schizophrenia Candidate Regions on Chromosomes 5q, 6q, 10p, and 13q: Schizophrenia Linkage Collaborative Group III. American Journal of Human Genetics, 67:652-663.

•  Ewen, K.R., Bahlo, M., Treloar , S.A. , Levinson, D.F., MOWRY, B.J., Barlow, J.W., and Foote S.J. (2000). Identification and Analysis of Error Types in High-Throughput Genotyping. American Journal of Human Genetics , 67:727-736.

•  MOWRY, B.J., Nancarrow, D.J., Ewen, K., Lennon, D.P., Nertney, D.A., Jones, H.L., O'Brien, M.S., Thornley, C.E., Walters, M.L., Crowe, R.R., Silverman, J.M., Enicott, J., Sharpe, L., Hayward, N.K., Gladis, M.M., Foote, S.J., Levinson, D.F. (2000). Second stage of a genome scan of schizophrenia: study of five positive regions in an expanded sample. American Journal of Medical Genetics. (Neuropsychiatric Genetics) 96:864-69.

•  MOWRY, B.J., and Nancarrow, D.J. (2001). The molecular genetics of schizophrenia. Clinical and Experimental Pharmacology and Physiology , 28:66-69.

•  Sanders, A.R., Cao, Q., Taylor, J., Levin, T.E., Badner, J.A., Cravchik, A., Comeron, J.M., Naruya, S., Del Rosario, A., Salvi, D.A., Walczyk, K.A., MOWRY, B.J., Levinson, D.F., Crowe, R.R., Silverman, J.M., and Gejman, P.V. (2001). Genetic diversity of the human serotonin receptor 1B (HTR1B) gene. Genomics, 72:1-14.

•  McGrath, J., El-Saadi, O., Cardy, S., Chapple, B., Chant, D. and MOWRY, B. (2001). Urban birth and migrant status as risk factors for psychosis: an Australian case-control study. Soc Psychiatry Psychiatr Epidemiol , 36:533-536.

•  Levinson, D.F., Holmans, P.A., Laurent, C., Riley, B., Pulver, A.E., Gejman, P.V., Schwab, S.G., Williams, N.M., Owen, M.J., Wildenauer, D.B., Sanders, A.R., Nestadt, G., MOWRY, B.J., Wormley, B., Bauch é, S., Soubigou, S., Ribble, R., Nertney, D.A., Liang, K.Y., Martinolich, L., Maier, W., Norton, Nadine., Williams, H., Albus, M., Carpenter, B., deMarchi, N., Ewen-Whnite, K.R., Walsh, D., Jay, M., Deleuze, J.F., O'Neill, A.F., Papadimitriou, G., Weilbaecher, A., Lerer, B., O'Donovan M.C., Dikeos, D., Silverman, J.M., Kendler, K.S., Mallet, J., Crowe, R.R., Walters, M. (2002). No major schizophrenia locus detected on chromosome 1q in a large multicenter sample. Science, 296:739-741.

•  Chant, D., MOWRY, B., and McGrath, J. (2002). Assessing the co-segregation of disorders within pedigrees: a comparison of two methods. Australasian Epidemiologist . 1:29-33.

•  McGrath, J., El-Saadi, O., Grim, V., Cardy, S., Chapple, B., Chant, D., Lieberman, D. and MOWRY, B. (2002). Minor physical anomalies and quantitative measures of the head and face in psychosis. Archives of General Psychiatry, 59:458-64.

•  MOWRY, B. (2002). Finding disease genes in schizophrenia. Today's Life Science , 14(5): 34-38.

•  MOWRY, B. (2003), Psychiatric Genetics in Australia . Psychiatric Genetics 13:131-141.

•  Levinson, D., MOWRY, B., Escamilla, M., and Faraone, S (2002). The Lifetime Dimensions of Psychosis Scale (LDPS): Description and Inter-rater Reliability. Schizophrenia Bulletin, 28(4):683-95.

•  Handoko, H., Nancarrow, D., Hayward , N., Ohaeri, J., McGrath, J., Levinson, D., Johns, C., Walters, M., Nertney, D., and MOWRY, B. (2003). Tumor necrosis factor haplotype analysis amongst schizophrenia probands from four distinct populations in the Asia-Pacific region. American Journal of Medical Genetics (Neuropsychiatric Genetics) 121B:1-6.

•  Lewis, C.M., Levinson, D.F., Wise, L.H., DeLisi, L.E., Straub, R.E., Hovatta, I., Williams, N.M., Schwab, S.G., Pulver, A.E., Faraone, S.V., Brzustowicz, L.M., Kaufmann, C.A., Garver, D.L., Gurling, H.M.D., Lindholm, E., Coon, H., Moises, H.W., Byerley, W., Shaw, S.H., Mesen, A., Sherrington, R., O'Neill, F.A., Walsh, D., Kendler, K.S., Ekeland, J., Paunio, T., Lönnqvist, J., Peltonen, L., O'Donovan, M.C., Owen, M.J., Wildenauer, D.B., Maier, W., Nestadt, G., Blouin, J.L., Antonarakis, S.E., MOWRY, B.J., Silverman, J.M., Crowe, R.R., Cloninger, C. R., Tsuang, M.T., Malaspina, D., Harkavy-Friedman, J.M., Savrakic, D.M., Bassett, A.S., Holcomb, J., Kalsi, G., McQuillin, A., Brynjolfson, J., Sigmundsson, T., Petursson, H., Jazin, E., Zoëga T., Helgason, T. (2003). Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. American Journal of Human Genetics 73:34-48.

•  McGrath, J., Eyles, D., MOWRY, B., Yolken, R., Buka, S. (2003). Low maternal vitamin D as a risk factor for schizophrenia: a pilot study using banked sera. Schizophrenia Res 63:73-78.

•  Duan, J.R., Sanders, Alan R., Molen Jane E.V., Martinolich L., MOWRY, B.J., Levinson Douglas F., Crowe Raymond R., Silverman Jeremy M., Gejman Pablo V. (2003). Polymorphisms in the 5'–untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression. Molecular Psychiatry 8:901-910.

•  Sukanta, S., Loesch, D., Chant, D., Welham, J., ElSaddi, O., Fan?ana?s, L., MOWRY, B.J ., McGrath, J. (2004). Directional and fluctuating asymmetry in finger and a-b ridge counts in psychosis: a case-control study BioMed Central. 3:3

•  MOWRY, Bryan J ., Holmans P.A., Pulver, A.E., Gejman, P.V., Riley, B., Williams, N.M., Laurent, C., Schwab, S.G., Wildenauer, D.B., Bauché, S., Owen, M.J., Wormley, B., Sanders, A.R., Nestadt ,G., Liang, K.Y., Duan ,J., Ribble, R., Norton, N., Soubigou, S., Maier, W., Ewen-White, K.R., demarche, N., Carpenter, B., Walsh, D., Williams, H., Jay, M., Albus, M., Nertney, D.A., Papadimitriou, G., O'Neill, A., O'Donovan, M. C., Deleuze, J.-F., Lerer, F.B., Dikeos, D., Kendler, K.S., Mallet, J., Silverman, J.M., Crowe, R.R., Levinson, D.F., (2004). Multicenter linkage study of schizophrenia loci on chromosome 22q. Molecular Psychiatry. 9:784-795.

•  Barrett, R., Loa,P., Jerah, E., Nancarrow, D., Chant D., MOWRY B.J. Rates of treated Schizophrenia and its clinical and cultural features in the population isolate of the Iban of the Swarawak: a tri-diagnostic approach. (2003) Psychological Medicine (In press – accepted Apr 20, 2004).

•  Duan, J., Martinez , M., Sanders, A.R., Hou C., Saitou, N., Kitano, K., MOWRY BJ., Crowe, R, Silverman, J., Levinson, D.P., Gejman, P. (2004). Polymorphisms in Trace Amine Receptor 4 ( TRAR4 ) are Associated with Susceptibility for schizophrenia on Chromosome 6q23.2. American Journal of Human Genetics Vol. 75:4:624-638

•  Handoko, H., Nyholt, D., Hayward , N., Nertney, D., Hannah, D., Windus, L., McCormack, C., Smith, H., Filippich, C., James, M., MOWRY, Bryan J. Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia. Molecular Psychiatry (In press – accepted September 15, 2004).

•  Jones, A.L., MOWRY, B.J . , Pender, M.P., Greer, J.M. (2005). Immune dysregulation and self-reactivity in schizophrenia: do some cases of schizophrenia have an autoimmune basis? Immunology and Cell Biology 83 (1): 9-17.

•  McGrath, J.J., MOWRY Bryan J., Whiteford, H. The Queensland Centre for Mental Health Research: the first seventeen years. Australian and New Zealand Journal of Psychiatry (In press – accepted December 23, 2004).

•  Holliday, E., MOWRY , Bryan J., Chant, D., Nyholt, D.(2005). The Importance of Modelling Heterogeneity in Complex Disease: Application to NIMH Schizophrenia Genetics Initiative Data. Human Genetics. (In press – accepted January 19, 2005).