LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia

C. Francks, S. Maegawa, J. Laurén, B. S. Abrahams, A. Velayos-Baeza, S. E. Medland, S. Colella, M. Groszer, E. Z. McAuley, T. M. Caffrey, T. Timmusk, P. Pruunsild, I. Koppel, P. A. Lind, N. Matsumoto-Itaba, J. Nicod, L. Xiong, R. Joober, W. Enard, B. Krinsky & 22 others E. Nanba, A. J. Richardson, B. P. Riley, N. G. Martin, S. M. Strittmatter, H. J. Möller, D. Rujescu, D. St. Clair, P. Muglia, J. L. Roos, S. E. Fisher, R. Wade-Martins, G. A. Rouleau, J. F. Stein, M. Karayiorgou, D. H. Geschwind, J. Ragoussis, K. S. Kendler, M. S. Airaksinen, M. Oshimura, L. E. Delisi, A. P. Monaco

Research output: Contribution to journalArticle

229 Citations (Scopus)

Abstract

Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.

Original languageEnglish (US)
Pages (from-to)1129-1139
Number of pages11
JournalMolecular Psychiatry
Volume12
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Functional Laterality
Chromosomes, Human, Pair 1
Leucine
Schizophrenia
Genes
Haplotypes
Brain
Prosencephalon
Psychotic Disorders
Cognition
Emotions
Down-Regulation
Mothers

Keywords

  • Association
  • Brain asymmetry
  • Handedness
  • Imprinted gene
  • Schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health

Cite this

Francks, C., Maegawa, S., Laurén, J., Abrahams, B. S., Velayos-Baeza, A., Medland, S. E., ... Monaco, A. P. (2007). LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. Molecular Psychiatry, 12(12), 1129-1139. https://doi.org/10.1038/sj.mp.4002053

LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. / Francks, C.; Maegawa, S.; Laurén, J.; Abrahams, B. S.; Velayos-Baeza, A.; Medland, S. E.; Colella, S.; Groszer, M.; McAuley, E. Z.; Caffrey, T. M.; Timmusk, T.; Pruunsild, P.; Koppel, I.; Lind, P. A.; Matsumoto-Itaba, N.; Nicod, J.; Xiong, L.; Joober, R.; Enard, W.; Krinsky, B.; Nanba, E.; Richardson, A. J.; Riley, B. P.; Martin, N. G.; Strittmatter, S. M.; Möller, H. J.; Rujescu, D.; St. Clair, D.; Muglia, P.; Roos, J. L.; Fisher, S. E.; Wade-Martins, R.; Rouleau, G. A.; Stein, J. F.; Karayiorgou, M.; Geschwind, D. H.; Ragoussis, J.; Kendler, K. S.; Airaksinen, M. S.; Oshimura, M.; Delisi, L. E.; Monaco, A. P.

In: Molecular Psychiatry, Vol. 12, No. 12, 12.2007, p. 1129-1139.

Research output: Contribution to journalArticle

Francks, C, Maegawa, S, Laurén, J, Abrahams, BS, Velayos-Baeza, A, Medland, SE, Colella, S, Groszer, M, McAuley, EZ, Caffrey, TM, Timmusk, T, Pruunsild, P, Koppel, I, Lind, PA, Matsumoto-Itaba, N, Nicod, J, Xiong, L, Joober, R, Enard, W, Krinsky, B, Nanba, E, Richardson, AJ, Riley, BP, Martin, NG, Strittmatter, SM, Möller, HJ, Rujescu, D, St. Clair, D, Muglia, P, Roos, JL, Fisher, SE, Wade-Martins, R, Rouleau, GA, Stein, JF, Karayiorgou, M, Geschwind, DH, Ragoussis, J, Kendler, KS, Airaksinen, MS, Oshimura, M, Delisi, LE & Monaco, AP 2007, 'LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia', Molecular Psychiatry, vol. 12, no. 12, pp. 1129-1139. https://doi.org/10.1038/sj.mp.4002053
Francks, C. ; Maegawa, S. ; Laurén, J. ; Abrahams, B. S. ; Velayos-Baeza, A. ; Medland, S. E. ; Colella, S. ; Groszer, M. ; McAuley, E. Z. ; Caffrey, T. M. ; Timmusk, T. ; Pruunsild, P. ; Koppel, I. ; Lind, P. A. ; Matsumoto-Itaba, N. ; Nicod, J. ; Xiong, L. ; Joober, R. ; Enard, W. ; Krinsky, B. ; Nanba, E. ; Richardson, A. J. ; Riley, B. P. ; Martin, N. G. ; Strittmatter, S. M. ; Möller, H. J. ; Rujescu, D. ; St. Clair, D. ; Muglia, P. ; Roos, J. L. ; Fisher, S. E. ; Wade-Martins, R. ; Rouleau, G. A. ; Stein, J. F. ; Karayiorgou, M. ; Geschwind, D. H. ; Ragoussis, J. ; Kendler, K. S. ; Airaksinen, M. S. ; Oshimura, M. ; Delisi, L. E. ; Monaco, A. P. / LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia. In: Molecular Psychiatry. 2007 ; Vol. 12, No. 12. pp. 1129-1139.
@article{86d3383850b043c084a55cf8f233f6a1,
title = "LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia",
abstract = "Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.",
keywords = "Association, Brain asymmetry, Handedness, Imprinted gene, Schizophrenia",
author = "C. Francks and S. Maegawa and J. Laur{\'e}n and Abrahams, {B. S.} and A. Velayos-Baeza and Medland, {S. E.} and S. Colella and M. Groszer and McAuley, {E. Z.} and Caffrey, {T. M.} and T. Timmusk and P. Pruunsild and I. Koppel and Lind, {P. A.} and N. Matsumoto-Itaba and J. Nicod and L. Xiong and R. Joober and W. Enard and B. Krinsky and E. Nanba and Richardson, {A. J.} and Riley, {B. P.} and Martin, {N. G.} and Strittmatter, {S. M.} and M{\"o}ller, {H. J.} and D. Rujescu and {St. Clair}, D. and P. Muglia and Roos, {J. L.} and Fisher, {S. E.} and R. Wade-Martins and Rouleau, {G. A.} and Stein, {J. F.} and M. Karayiorgou and Geschwind, {D. H.} and J. Ragoussis and Kendler, {K. S.} and Airaksinen, {M. S.} and M. Oshimura and Delisi, {L. E.} and Monaco, {A. P.}",
year = "2007",
month = "12",
doi = "10.1038/sj.mp.4002053",
language = "English (US)",
volume = "12",
pages = "1129--1139",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia

AU - Francks, C.

AU - Maegawa, S.

AU - Laurén, J.

AU - Abrahams, B. S.

AU - Velayos-Baeza, A.

AU - Medland, S. E.

AU - Colella, S.

AU - Groszer, M.

AU - McAuley, E. Z.

AU - Caffrey, T. M.

AU - Timmusk, T.

AU - Pruunsild, P.

AU - Koppel, I.

AU - Lind, P. A.

AU - Matsumoto-Itaba, N.

AU - Nicod, J.

AU - Xiong, L.

AU - Joober, R.

AU - Enard, W.

AU - Krinsky, B.

AU - Nanba, E.

AU - Richardson, A. J.

AU - Riley, B. P.

AU - Martin, N. G.

AU - Strittmatter, S. M.

AU - Möller, H. J.

AU - Rujescu, D.

AU - St. Clair, D.

AU - Muglia, P.

AU - Roos, J. L.

AU - Fisher, S. E.

AU - Wade-Martins, R.

AU - Rouleau, G. A.

AU - Stein, J. F.

AU - Karayiorgou, M.

AU - Geschwind, D. H.

AU - Ragoussis, J.

AU - Kendler, K. S.

AU - Airaksinen, M. S.

AU - Oshimura, M.

AU - Delisi, L. E.

AU - Monaco, A. P.

PY - 2007/12

Y1 - 2007/12

N2 - Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.

AB - Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.

KW - Association

KW - Brain asymmetry

KW - Handedness

KW - Imprinted gene

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=36549060114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36549060114&partnerID=8YFLogxK

U2 - 10.1038/sj.mp.4002053

DO - 10.1038/sj.mp.4002053

M3 - Article

VL - 12

SP - 1129

EP - 1139

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 12

ER -