CMIP and ATP2C2 modulate phonological short-term memory in language impairment

Dianne F. Newbury, Laura Winchester, Laura Addis, Silvia Paracchini, Lyn-Louise Buckingham, Ann Clark, Wendy Cohen, Hilary Cowie, Katharina Dworzynski, Andrea Everitt, Ian M. Goodyer, Elizabeth Hennessy, A. David Kindley, Laura L. Miller, Jamal Nasir, Anne O'Hare, Duncan Shaw, Zoe Simkin, Emily Simonoff, Vicky Slonims & 11 others Jocelynne Watson, Jiannis Ragoussis, Simon E. Fisher, Jonathon R. Seckl, Peter J. Helms, Patrick F. Bolton, Andrew Pickles, Gina Conti-Ramsden, Gillian Baird, Dorothy V.M. Bishop, Anthony P. Monaco

Research output: Contribution to journalArticle

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Abstract

Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.
LanguageEnglish
Pages264-272
Number of pages9
JournalAmerican Journal of Human Genetics
Volume85
Issue number2
Early online date30 Jul 2009
DOIs
Publication statusPublished - 14 Aug 2009

Fingerprint

Short-Term Memory
Language
Proto-Oncogene Proteins c-maf
Aptitude
Calcium-Transporting ATPases
Chromosomes

Keywords

  • speech and language therapy
  • specific language impairment
  • language therapy

Cite this

Newbury, D. F., Winchester, L., Addis, L., Paracchini, S., Buckingham, L-L., Clark, A., ... Monaco, A. P. (2009). CMIP and ATP2C2 modulate phonological short-term memory in language impairment. American Journal of Human Genetics, 85(2), 264-272. https://doi.org/10.1016/j.ajhg.2009.07.004
Newbury, Dianne F. ; Winchester, Laura ; Addis, Laura ; Paracchini, Silvia ; Buckingham, Lyn-Louise ; Clark, Ann ; Cohen, Wendy ; Cowie, Hilary ; Dworzynski, Katharina ; Everitt, Andrea ; Goodyer, Ian M. ; Hennessy, Elizabeth ; Kindley, A. David ; Miller, Laura L. ; Nasir, Jamal ; O'Hare, Anne ; Shaw, Duncan ; Simkin, Zoe ; Simonoff, Emily ; Slonims, Vicky ; Watson, Jocelynne ; Ragoussis, Jiannis ; Fisher, Simon E. ; Seckl, Jonathon R. ; Helms, Peter J. ; Bolton, Patrick F. ; Pickles, Andrew ; Conti-Ramsden, Gina ; Baird, Gillian ; Bishop, Dorothy V.M. ; Monaco, Anthony P. / CMIP and ATP2C2 modulate phonological short-term memory in language impairment. In: American Journal of Human Genetics. 2009 ; Vol. 85, No. 2. pp. 264-272.
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abstract = "Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.",
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Newbury, DF, Winchester, L, Addis, L, Paracchini, S, Buckingham, L-L, Clark, A, Cohen, W, Cowie, H, Dworzynski, K, Everitt, A, Goodyer, IM, Hennessy, E, Kindley, AD, Miller, LL, Nasir, J, O'Hare, A, Shaw, D, Simkin, Z, Simonoff, E, Slonims, V, Watson, J, Ragoussis, J, Fisher, SE, Seckl, JR, Helms, PJ, Bolton, PF, Pickles, A, Conti-Ramsden, G, Baird, G, Bishop, DVM & Monaco, AP 2009, 'CMIP and ATP2C2 modulate phonological short-term memory in language impairment' American Journal of Human Genetics, vol. 85, no. 2, pp. 264-272. https://doi.org/10.1016/j.ajhg.2009.07.004

CMIP and ATP2C2 modulate phonological short-term memory in language impairment. / Newbury, Dianne F.; Winchester, Laura; Addis, Laura; Paracchini, Silvia; Buckingham, Lyn-Louise; Clark, Ann; Cohen, Wendy; Cowie, Hilary; Dworzynski, Katharina; Everitt, Andrea; Goodyer, Ian M.; Hennessy, Elizabeth; Kindley, A. David; Miller, Laura L.; Nasir, Jamal; O'Hare, Anne; Shaw, Duncan; Simkin, Zoe; Simonoff, Emily; Slonims, Vicky; Watson, Jocelynne; Ragoussis, Jiannis; Fisher, Simon E.; Seckl, Jonathon R.; Helms, Peter J.; Bolton, Patrick F.; Pickles, Andrew; Conti-Ramsden, Gina; Baird, Gillian; Bishop, Dorothy V.M.; Monaco, Anthony P.

In: American Journal of Human Genetics, Vol. 85, No. 2, 14.08.2009, p. 264-272.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CMIP and ATP2C2 modulate phonological short-term memory in language impairment

AU - Newbury, Dianne F.

AU - Winchester, Laura

AU - Addis, Laura

AU - Paracchini, Silvia

AU - Buckingham, Lyn-Louise

AU - Clark, Ann

AU - Cohen, Wendy

AU - Cowie, Hilary

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AU - Everitt, Andrea

AU - Goodyer, Ian M.

AU - Hennessy, Elizabeth

AU - Kindley, A. David

AU - Miller, Laura L.

AU - Nasir, Jamal

AU - O'Hare, Anne

AU - Shaw, Duncan

AU - Simkin, Zoe

AU - Simonoff, Emily

AU - Slonims, Vicky

AU - Watson, Jocelynne

AU - Ragoussis, Jiannis

AU - Fisher, Simon E.

AU - Seckl, Jonathon R.

AU - Helms, Peter J.

AU - Bolton, Patrick F.

AU - Pickles, Andrew

AU - Conti-Ramsden, Gina

AU - Baird, Gillian

AU - Bishop, Dorothy V.M.

AU - Monaco, Anthony P.

PY - 2009/8/14

Y1 - 2009/8/14

N2 - Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.

AB - Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.

KW - speech and language therapy

KW - specific language impairment

KW - language therapy

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Newbury DF, Winchester L, Addis L, Paracchini S, Buckingham L-L, Clark A et al. CMIP and ATP2C2 modulate phonological short-term memory in language impairment. American Journal of Human Genetics. 2009 Aug 14;85(2):264-272. https://doi.org/10.1016/j.ajhg.2009.07.004