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Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: unique and shared genetic effects.
Mol Psychiatry. 2004 May; 9(5):485-93.MP

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are common highly heritable disorders of childhood, which frequently co-occur. Data from twin and family studies suggest that this overlap is, in part, due to shared genetic underpinnings. Here, we report the first genome-wide linkage analysis of measures of reading ability in children with ADHD, using a sample of 233 affected sibling pairs who previously participated in a genome-wide scan for susceptibility loci in ADHD. Quantitative trait locus (QTL) analysis of a composite reading factor defined from three highly correlated reading measures identified suggestive linkage (multipoint maximum lod score, MLS>2.2) in four chromosomal regions. Two regions (16p, 17q) overlap those implicated by our previous genome-wide scan for ADHD in the same sample: one region (2p) provides replication for an RD susceptibility locus, and one region (10q) falls approximately 35 cM from a modestly highlighted region in an independent genome-wide scan of siblings with ADHD. Investigation of an individual reading measure of Reading Recognition supported linkage to putative RD susceptibility regions on chromosome 8p (MLS=2.4) and 15q (MLS=1.38). Thus, the data support the existence of genetic factors that have pleiotropic effects on ADHD and reading ability--as suggested by shared linkages on 16p, 17q and possibly 10q--but also those that appear to be unique to reading--as indicated by linkages on 2p, 8p and 15q that coincide with those previously found in studies of RD. Our study also suggests that reading measures may represent useful phenotypes in ADHD research. The eventual identification of genes underlying these unique and shared linkages may increase our understanding of ADHD, RD and the relationship between the two.

Authors+Show Affiliations

Center for Neurobehavioral Genetics, University of California, Los Angeles, USA. sloo@mednet.ucla.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14625563

Citation

Loo, S K., et al. "Genome-wide Scan of Reading Ability in Affected Sibling Pairs With Attention-deficit/hyperactivity Disorder: Unique and Shared Genetic Effects." Molecular Psychiatry, vol. 9, no. 5, 2004, pp. 485-93.
Loo SK, Fisher SE, Francks C, et al. Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: unique and shared genetic effects. Mol Psychiatry. 2004;9(5):485-93.
Loo, S. K., Fisher, S. E., Francks, C., Ogdie, M. N., MacPhie, I. L., Yang, M., McCracken, J. T., McGough, J. J., Nelson, S. F., Monaco, A. P., & Smalley, S. L. (2004). Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: unique and shared genetic effects. Molecular Psychiatry, 9(5), 485-93.
Loo SK, et al. Genome-wide Scan of Reading Ability in Affected Sibling Pairs With Attention-deficit/hyperactivity Disorder: Unique and Shared Genetic Effects. Mol Psychiatry. 2004;9(5):485-93. PubMed PMID: 14625563.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: unique and shared genetic effects. AU - Loo,S K, AU - Fisher,S E, AU - Francks,C, AU - Ogdie,M N, AU - MacPhie,I L, AU - Yang,M, AU - McCracken,J T, AU - McGough,J J, AU - Nelson,S F, AU - Monaco,A P, AU - Smalley,S L, PY - 2003/11/20/pubmed PY - 2004/12/23/medline PY - 2003/11/20/entrez SP - 485 EP - 93 JF - Molecular psychiatry JO - Mol Psychiatry VL - 9 IS - 5 N2 - Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are common highly heritable disorders of childhood, which frequently co-occur. Data from twin and family studies suggest that this overlap is, in part, due to shared genetic underpinnings. Here, we report the first genome-wide linkage analysis of measures of reading ability in children with ADHD, using a sample of 233 affected sibling pairs who previously participated in a genome-wide scan for susceptibility loci in ADHD. Quantitative trait locus (QTL) analysis of a composite reading factor defined from three highly correlated reading measures identified suggestive linkage (multipoint maximum lod score, MLS>2.2) in four chromosomal regions. Two regions (16p, 17q) overlap those implicated by our previous genome-wide scan for ADHD in the same sample: one region (2p) provides replication for an RD susceptibility locus, and one region (10q) falls approximately 35 cM from a modestly highlighted region in an independent genome-wide scan of siblings with ADHD. Investigation of an individual reading measure of Reading Recognition supported linkage to putative RD susceptibility regions on chromosome 8p (MLS=2.4) and 15q (MLS=1.38). Thus, the data support the existence of genetic factors that have pleiotropic effects on ADHD and reading ability--as suggested by shared linkages on 16p, 17q and possibly 10q--but also those that appear to be unique to reading--as indicated by linkages on 2p, 8p and 15q that coincide with those previously found in studies of RD. Our study also suggests that reading measures may represent useful phenotypes in ADHD research. The eventual identification of genes underlying these unique and shared linkages may increase our understanding of ADHD, RD and the relationship between the two. SN - 1359-4184 UR - https://www.unboundmedicine.com/medline/citation/14625563/Genome_wide_scan_of_reading_ability_in_affected_sibling_pairs_with_attention_deficit/hyperactivity_disorder:_unique_and_shared_genetic_effects_ L2 - https://doi.org/10.1038/sj.mp.4001450 DB - PRIME DP - Unbound Medicine ER -