Increasing the Number of SNP loci does not Necessarily Improve Prediction Power at Least in the Comparison of MTHFR SNP and Haplotypes

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Author(s)

    • MIYAKI Koichi
    • Preventive Medicine for Cerebrovascular Disease, Department of Neurology, School of Medicine, Keio University
    • TAKAHASHI Yoshimitsu
    • Department of Health Informatics, School of Public Health, Graduate School of Medicine, Kyoto University
    • SONG Yixuan
    • Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
    • ZHANG Ling
    • Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
    • MURAMATSU Masaaki
    • Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University
    • NAKAYAMA Takeo
    • Department of Health Informatics, School of Public Health, Graduate School of Medicine, Kyoto University

Abstract

<B>Background:</B> Rapid advances in genotyping technology have made it possible to easily utilize a large number of genetic markers. According to information theory, an increase in the number of markers provides more information; however, the clinical usefulness does not increase linearly. This study aimed to assess the effect of folic acid supplementation quantitatively in <I>MTHFR</I> haplotypes, and compare its prediction power with that of the C677T single nucleotide polymorphism (SNP) alone.<BR><B>Methods:</B> The study was a randomized, double-blind, placebo-controlled trial, designed in accordance with the CONSORT statement. The participants were 202 healthy Japanese males who were administered either folic acid at 1 mg/day or a placebo postoperatively for 3 months. The primary endpoint was the total plasma homocysteine levels (tHcy). Stratified analysis by HapMap-based tag SNPs was performed.<BR><B>Results:</B> Of 52 SNPs on the <I>MTHFR</I> gene, 4 SNP loci covering more than 80% of the information were selected, and the haplotypes were estimated. The haplotypes were classified into 3 groups (Hap0, Hap1, and Hap2), on the basis of the number of times the most frequent haplotype was present. The greatest decrease was observed in Hap2 (6.61 µmol/L), compared with the other haplotypes (Hap0, 2.67; Hap1, 2.60) (trend test, <I>P</I> < 0.01). The haplotype information obtained was not more informative than that obtained with grouping by a single SNP, C677T, which strongly influences enzyme activity.<BR><B>Conclusions:</B> Grouping by the C677T SNP alone was almost as good a predictor of the homocysteine-lowering effects as was grouping by the 4 best SNPs. This shows that increasing the number of typed SNPs does not necessarily provide more information, at least for this gene. A more efficient, cost-informative method for analyzing genomic data is required.

Journal

  • Journal of Epidemiology

    Journal of Epidemiology 18(6), 243-250, 2008-11-01

    Japan Epidemiological Association

References:  24

Codes

  • NII Article ID (NAID)
    10024796805
  • NII NACSIS-CAT ID (NCID)
    AA10952696
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09175040
  • Data Source
    CJP  CJPref  J-STAGE 
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