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; 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

doi:10.1016/j.ajhg.2009.07.004

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 SlonimsJocelynne 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

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146 Citations (Scopus)

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 SLI 1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 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.

Original language	English
Pages (from-to)	264 - 272
Number of pages	9
Journal	American Journal of Human Genetics
Volume	85
Issue number	2
DOIs	https://doi.org/10.1016/j.ajhg.2009.07.004
Publication status	Published - 14 Aug 2009

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Newbury, D. F., Winchester, L., Addis, L., Paracchini, S., Buckingham, L.-L., Clark, A., Cohen, W., Cowie, H., Dworzynski, K., Everitt, A., Goodyer, I. M., Hennessy, E., Kindley, A. D., Miller, L. L., Nasir, J., O'Hare, A., Shaw, D., Simkin, Z., Simonoff, E., ... 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

@article{4df5338dd77a4c19a10ae9a360745407,

title = "CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment",

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 SLI 1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 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.",

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

year = "2009",

month = aug,

day = "14",

doi = "10.1016/j.ajhg.2009.07.004",

language = "English",

volume = "85",

pages = "264 -- 272",

journal = "American Journal of Human Genetics",

issn = "1537-6605",

publisher = "Elsevier",

number = "2",

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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

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

AU - Dworzynski, Katharina

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 SLI 1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 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 SLI 1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 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.

U2 - 10.1016/j.ajhg.2009.07.004

DO - 10.1016/j.ajhg.2009.07.004

M3 - Article

SN - 1537-6605

VL - 85

SP - 264

EP - 272

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 2

ER -

CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment

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