Human Molecular Genetics Advance Access published online on March 30, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi142
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Social, Genetic and Developmental Psychiatry Centre, Box Number P082, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, United Kingdom
* To whom correspondence should be addressed. Mild mental impairment (MMI) represents the low extreme of the quantitative trait of general intelligence and is highly heritable. Quantitative trait loci (QTLs) conferring susceptibility to MMI, as for most complex traits, are likely to be of small effect size. Using a novel approach we call SNP-MaP (SNP Microarrays and Pooling), we have identified four loci associated with MMI. These four loci have been replicated in two SNP-MaP studies and verified by individual genotyping. The two SNP-MaP studies conducted were a case vs. control comparison (n=515 & n=1,028, respectively), and a low vs. high general intelligence extremes group comparison (n=503 & n=505, respectively). Each of the four groups consisted of five independent ‘sub-pools’, with each sub-pool assayed on a separate microarray. Twelve loci showing the largest significant differences in both SNP-MaP studies were individually genotyped on 6,154 children. Of the four loci positively associated with MMI, the minor allele of each conferred the greater risk for MMI. Two of the loci are close to known genes and may be in linkage disequilibrium with them. One of the loci is between the candidate genes KLF7 and CREB1, but given possible long-range effects on expression and the unknown importance of untranslated elements such as micro RNAs, all four loci deserve attention as candidates. Although each SNP accounts for a small amount of variance, their effects are additive and they can be combined in a ‘SNP set’ that can be used as a genetic risk index for MMI in behavioral genomic analyses.
Article
SNPs, microarrays, and pooled DNA: identification of four loci associated with mild mental impairment in a sample of 6,000 children
2 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, SE5 8AF, UK
Lee M. Butcher, E-mail: l.butcher{at}iop.kcl.ac.uk
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Macgregor, Z. Z. Zhao, A. Henders, N. G. Martin, G. W. Montgomery, and P. M. Visscher Highly cost-efficient genome-wide association studies using DNA pools and dense SNP arrays Nucleic Acids Res., April 1, 2008; 36(6): e35 - e35. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Uhl, T. Drgon, Q.-R. Liu, C. Johnson, D. Walther, T. Komiyama, M. Harano, Y. Sekine, T. Inada, N. Ozaki, et al. Genome-Wide Association for Methamphetamine Dependence: Convergent Results From 2 Samples Arch Gen Psychiatry, March 1, 2008; 65(3): 345 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Byun, S. J. Caillier, X. Montalban, P. Villoslada, O. Fernandez, D. Brassat, M. Comabella, J. Wang, L. F. Barcellos, S. E. Baranzini, et al. Genome-Wide Pharmacogenomic Analysis of the Response to Interferon Beta Therapy in Multiple Sclerosis Arch Neurol, March 1, 2008; 65(3): 337 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Johnson Bayesian method for gene detection and mapping, using a case and control design and DNA pooling Biostat., July 1, 2007; 8(3): 546 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Huentelman, A. Papassotiropoulos, D. W. Craig, F. J. Hoerndli, J. V. Pearson, K.-D. Huynh, J. Corneveaux, J. Hanggi, C. R.A. Mondadori, A. Buchmann, et al. Calmodulin-binding transcription activator 1 (CAMTA1) alleles predispose human episodic memory performance Hum. Mol. Genet., June 15, 2007; 16(12): 1469 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Hanson, D. W. Craig, M. P. Millis, K. A. Yeatts, S. Kobes, J. V. Pearson, A. M. Lee, W. C. Knowler, R. G. Nelson, and J. K. Wolford Identification of PVT1 as a Candidate Gene for End-Stage Renal Disease in Type 2 Diabetes Using a Pooling-Based Genome-Wide Single Nucleotide Polymorphism Association Study Diabetes, April 1, 2007; 56(4): 975 - 983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Meaburn, L. M. Butcher, L. C. Schalkwyk, and R. Plomin Genotyping pooled DNA using 100K SNP microarrays: a step towards genomewide association scans Nucleic Acids Res., February 14, 2006; 34(4): e28 - e28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Brohede, R. Dunne, J. D. McKay, and G. N. Hannan PPC: an algorithm for accurate estimation of SNP allele frequencies in small equimolar pools of DNA using data from high density microarrays Nucleic Acids Res., September 30, 2005; 33(17): e142 - e142. [Abstract] [Full Text] [PDF]
|
|