Article thumbnail

Comparison of the power of haplotype-based versus single- and multilocus association methods for gene × environment (gene × sex) interactions and application to gene × smoking and gene × sex interactions in rheumatoid arthritis

By Astrid Dempfle, Rebecca Hein, Lars Beckmann, André Scherag, Thuy Trang Nguyen, Helmut Schäfer and Jenny Chang-Claude


Accounting for interactions with environmental factors in association studies may improve the power to detect genetic effects and may help identifying important environmental effect modifiers. The power of unphased genotype-versus haplotype-based methods in regions with high linkage disequilibrium (LD), as measured by D', for analyzing gene × environment (gene × sex) interactions was compared using the Genetic Analysis Workshop 15 (GAW15) simulated data on rheumatoid arthritis with prior knowledge of the answers. Stepwise and regular conditional logistic regression (CLR) was performed using a matched case-control sample for a HLA region interacting with sex. Haplotype-based analyses were performed using a haplotype-sharing-based Mantel statistic and a test for haplotype-trait association in a general linear model framework. A step-down minP algorithm was applied to derive adjusted p-values and to allow for power comparisons. These methods were also applied to the GAW15 real data set for PTPN22

Topics: Proceedings
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (1998). Applied Regression Analysis
  2. (2006). Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients. Arthritis Res Ther
  3. (2004). Cardon LR: The complex interplay among factors that influence allelic association. Nat Rev Genet
  4. (1989). Data Analysis: A Model-Comparison Approach
  5. (2002). DG: A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes.
  6. (2003). DJ: Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered
  7. (1992). forward and stepwise automated subset selection algorithms: frequency of obtaining authentic and noise variables.
  8. (2002). GA: Score tests for association between traits and haplotypes when linkage phase is ambiguous.
  9. (2005). Gene-environment interactions in human diseases.
  10. (2001). Habbema JD: Prognostic modeling with logistic regression analysis: in search of a sensible strategy in small data sets. Med Decis Making
  11. (2005). Haplotype sharing analysis using Mantel statistics. Hum Hered
  12. (2005). L: SDMinP: a program to control the family wise error rate using stepdown minP adjusted P-values. Bioinformatics
  13. (2004). PK: A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis.
  14. (2005). PK: PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis.
  15. (2005). Rioux JD: Replication of putative candidate-gene associations with rheumatoid arthritis in >4,000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4.
  16. (2002). Saag KG: Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women's Health Study.