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Sampson JN, Wheeler B, Li P, et al. LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS. Ann Appl Stat. 2014;8(2):974-998doi: 10.1214/14-aoas715.
Sampson, J. N., Wheeler, B., Li, P., & Shi, J. (2014). LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS. The annals of applied statistics, 8(2), 974-998. https://doi.org/10.1214/14-aoas715
Sampson, Joshua N, et al. "LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS." The annals of applied statistics vol. 8,2 (2014): 974-998. doi: https://doi.org/10.1214/14-aoas715
Sampson JN, Wheeler B, Li P, Shi J. LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS. Ann Appl Stat. 2014 Jun;8(2):974-998. doi: 10.1214/14-aoas715. PMID: 25544865; PMCID: PMC4275846.
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Ann Appl Stat. 2014 Jun;8(2):974-998. doi: 10.1214/14-aoas715.

LEVERAGING LOCAL IDENTITY-BY-DESCENT INCREASES THE POWER OF CASE/CONTROL GWAS WITH RELATED INDIVIDUALS.

The annals of applied statistics

Joshua N Sampson, Bill Wheeler, Peng Li, Jianxin Shi

Affiliations

  1. Division of Cancer Epidemiology and Genetics, National Cancer Institute.
  2. Information Management Services.

PMID: 25544865 PMCID: PMC4275846 DOI: 10.1214/14-aoas715

Abstract

Large case/control genome-wide association studies (GWAS) often include groups of related individuals with known relationships. When testing for associations at a given locus, current methods incorporate only the familial relationships between individuals. Here, we introduce the chromosome-based Quasi Likelihood Score (cQLS) statistic that incorporates local Identity-By-Descent (IBD) to increase the power to detect associations. In studies robust to population stratification, such as those with case/control sibling pairs, simulations show that the study power can be increased by over 50%. In our example, a GWAS examining late-onset Alzheimers disease, the p-values among the most strongly associated SNPs in the APOE gene tend to decrease, with the smallest p-value decreasing from 1.23 × 10

Keywords: GWAS; cQLS; case-control; related individuals

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