Set‐based tests for genetic association in longitudinal studies

Zihuai He, Min Zhang, Seunggeun Lee, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L. R. Kardia, Ana V. Diez Roux and Bhramar Mukherjee

Biometrics, 2015, vol. 71, issue 3, 606-615

Abstract: Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set of genetic variants. Generalized score type tests are developed, which we show are robust to misspecification of within‐subject correlation, a feature that is desirable for longitudinal analysis. In addition, a joint test incorporating gene–time interaction is further proposed. Computational advancement is made for scalable implementation of the proposed methods in large‐scale genome‐wide association studies (GWAS). The proposed methods are evaluated through extensive simulation studies and illustrated using data from the Multi‐Ethnic Study of Atherosclerosis (MESA). Our simulation results indicate substantial gain in power using LGRF when compared with two commonly used existing alternatives: (i) single marker tests using longitudinal outcome and (ii) existing gene‐based tests using the average value of repeated measurements as the outcome.

Date: 2015
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://doi.org/10.1111/biom.12310

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:bla:biomet:v:71:y:2015:i:3:p:606-615

Ordering information: This journal article can be ordered from
http://www.blackwell ... bs.asp?ref=0006-341X

Access Statistics for this article

More articles in Biometrics from The International Biometric Society
Bibliographic data for series maintained by Wiley Content Delivery ().