Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ

John D. Eicher, Natalie R. Powers, Laura L. Miller, Kathryn L. Mueller, Sara Mascheretti, Cecilia Marino, Erik G. Willcutt, John C. DeFries, Richard K. Olson, Shelley D. Smith, Bruce F. Pennington, J. Bruce Tomblin, Susan M. Ring, Jeffrey R. Gruen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.

Original languageEnglish
Pages (from-to)869-881
Number of pages13
JournalHuman Genetics
Volume133
Issue number7
DOIs
Publication statusPublished - 2014

Fingerprint

Reading
Language
Chromosomes
Genes
Cognition
Longitudinal Studies
Parents

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Eicher, J. D., Powers, N. R., Miller, L. L., Mueller, K. L., Mascheretti, S., Marino, C., ... Gruen, J. R. (2014). Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ. Human Genetics, 133(7), 869-881. https://doi.org/10.1007/s00439-014-1427-3

Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ. / Eicher, John D.; Powers, Natalie R.; Miller, Laura L.; Mueller, Kathryn L.; Mascheretti, Sara; Marino, Cecilia; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.; Smith, Shelley D.; Pennington, Bruce F.; Tomblin, J. Bruce; Ring, Susan M.; Gruen, Jeffrey R.

In: Human Genetics, Vol. 133, No. 7, 2014, p. 869-881.

Research output: Contribution to journalArticle

Eicher, JD, Powers, NR, Miller, LL, Mueller, KL, Mascheretti, S, Marino, C, Willcutt, EG, DeFries, JC, Olson, RK, Smith, SD, Pennington, BF, Tomblin, JB, Ring, SM & Gruen, JR 2014, 'Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ', Human Genetics, vol. 133, no. 7, pp. 869-881. https://doi.org/10.1007/s00439-014-1427-3
Eicher, John D. ; Powers, Natalie R. ; Miller, Laura L. ; Mueller, Kathryn L. ; Mascheretti, Sara ; Marino, Cecilia ; Willcutt, Erik G. ; DeFries, John C. ; Olson, Richard K. ; Smith, Shelley D. ; Pennington, Bruce F. ; Tomblin, J. Bruce ; Ring, Susan M. ; Gruen, Jeffrey R. / Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ. In: Human Genetics. 2014 ; Vol. 133, No. 7. pp. 869-881.
@article{49839428641e4366a2509a869cc0816f,
title = "Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ",
abstract = "Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.",
author = "Eicher, {John D.} and Powers, {Natalie R.} and Miller, {Laura L.} and Mueller, {Kathryn L.} and Sara Mascheretti and Cecilia Marino and Willcutt, {Erik G.} and DeFries, {John C.} and Olson, {Richard K.} and Smith, {Shelley D.} and Pennington, {Bruce F.} and Tomblin, {J. Bruce} and Ring, {Susan M.} and Gruen, {Jeffrey R.}",
year = "2014",
doi = "10.1007/s00439-014-1427-3",
language = "English",
volume = "133",
pages = "869--881",
journal = "Human Genetics",
issn = "0340-6717",
publisher = "Springer Verlag",
number = "7",

}

TY - JOUR

T1 - Characterization of the DYX2 locus on chromosome 6p22 with reading disability, language impairment, and IQ

AU - Eicher, John D.

AU - Powers, Natalie R.

AU - Miller, Laura L.

AU - Mueller, Kathryn L.

AU - Mascheretti, Sara

AU - Marino, Cecilia

AU - Willcutt, Erik G.

AU - DeFries, John C.

AU - Olson, Richard K.

AU - Smith, Shelley D.

AU - Pennington, Bruce F.

AU - Tomblin, J. Bruce

AU - Ring, Susan M.

AU - Gruen, Jeffrey R.

PY - 2014

Y1 - 2014

N2 - Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.

AB - Reading disability (RD) and language impairment (LI) are common neurodevelopmental disorders with moderately strong genetic components and lifelong implications. RD and LI are marked by unexpected difficulty acquiring and processing written and verbal language, respectively, despite adequate opportunity and instruction. RD and LI-and their associated deficits-are complex, multifactorial, and often comorbid. Genetic studies have repeatedly implicated the DYX2 locus, specifically the genes DCDC2 and KIAA0319, in RD, with recent studies suggesting they also influence LI, verbal language, and cognition. Here, we characterize the relationship of the DYX2 locus with RD, LI, and IQ. To accomplish this, we developed a marker panel densely covering the 1.4 Mb DYX2 locus and assessed association with reading, language, and IQ measures in subjects from the Avon Longitudinal Study of Parents and Children. We then replicated associations in three independent, disorder-selected cohorts. As expected, there were associations with known RD risk genes KIAA0319 and DCDC2. In addition, we implicated markers in or near other DYX2 genes, including TDP2, ACOT13, C6orf62, FAM65B, and CMAHP. However, the LD structure of the locus suggests that associations within TDP2, ACOT13, and C6orf62 are capturing a previously reported risk variant in KIAA0319. Our results further substantiate the candidacy of KIAA0319 and DCDC2 as major effector genes in DYX2, while proposing FAM65B and CMAHP as new DYX2 candidate genes. Association of DYX2 with multiple neurobehavioral traits suggests risk variants have functional consequences affecting multiple neurological processes. Future studies should dissect these functional, possibly interactive relationships of DYX2 candidate genes.

UR - http://www.scopus.com/inward/record.url?scp=84904125672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904125672&partnerID=8YFLogxK

U2 - 10.1007/s00439-014-1427-3

DO - 10.1007/s00439-014-1427-3

M3 - Article

VL - 133

SP - 869

EP - 881

JO - Human Genetics

JF - Human Genetics

SN - 0340-6717

IS - 7

ER -