Using Maximal Segmental Score in Genome-Wide Association Studies

Ying Chao Lin, Ching Lin Hsiao, Ai Ru Hsieh, Iebin Lian, Cathy S J Fann

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Genome-wide association studies (GWAS) have become the method of choice for identifying disease susceptibility genes in common disease genetics research. Despite successes in these studies, much of the heritability remains unexplained due to lack of power and low resolution. High-density genotyping arrays can now screen more than 5 million genetic markers. As a result, multiple comparison has become an important issue especially in the era of next-generation sequencing. We propose to use a two-stage maximal segmental score procedure (MSS) which uses region-specific empirical P-values to identify genomic segments most likely harboring the disease gene. We develop scoring systems based on Fisher's P-value combining method to convert locus-specific significance levels into region-specific scores. Through simulations, our result indicated that MSS increased the power to detect genetic association as compared with conventional methods provided type I error was at 5%. We demonstrated the application of MSS on a publicly available case-control dataset of Parkinson's disease and replicated the findings in the literature. MSS provides an efficient exploratory tool for high-density association data in the current era of next-generation sequencing. R source codes to implement the MSS procedure are freely available at http://www.csjfann.ibms.sinica.edu.tw/EAG/program/programlist.htm.

Original languageEnglish
Pages (from-to)594-601
Number of pages8
JournalGenetic Epidemiology
Volume36
Issue number6
DOIs
Publication statusPublished - 2012 Sep 1

Fingerprint

Genome-Wide Association Study
Genetic Research
Disease Susceptibility
Genetic Markers
Genes
Parkinson Disease

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Epidemiology

Cite this

Lin, Ying Chao ; Hsiao, Ching Lin ; Hsieh, Ai Ru ; Lian, Iebin ; Fann, Cathy S J. / Using Maximal Segmental Score in Genome-Wide Association Studies. In: Genetic Epidemiology. 2012 ; Vol. 36, No. 6. pp. 594-601.
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Using Maximal Segmental Score in Genome-Wide Association Studies. / Lin, Ying Chao; Hsiao, Ching Lin; Hsieh, Ai Ru; Lian, Iebin; Fann, Cathy S J.

In: Genetic Epidemiology, Vol. 36, No. 6, 01.09.2012, p. 594-601.

Research output: Contribution to journalArticle

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