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Journal article
Set-Based Tests for Genetic Association in Longitudinal Studies
Biometrics, v 71(3), pp 606-615
01 Sep 2015
PMID: 25854837
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Set-Based Tests for Genetic Association in Longitudinal Studies
- Creators
- Zihuai He - University of Michigan–Ann ArborMin Zhang - University of Michigan–Ann ArborSeunggeun Lee - University of Michigan–Ann ArborJennifer A. Smith - University of Michigan–Ann ArborXiuqing Guo - UCLA Medical CenterWalter Palmas - Columbia UniversitySharon L. R. Kardia - University of Michigan–Ann ArborAna V. Diez Roux - Drexel UniversityBhramar Mukherjee - University of Michigan–Ann Arbor
- Publication Details
- Biometrics, v 71(3), pp 606-615
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- R00HL113164; HL101161 / NIH/NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 2P60MD002249 / NIMHHD UL1RR024156 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) ES020811 / NIH/NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) N02-HL-64278 / NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R13HL095166 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) P60MD002249 / National Institute on Minority Health and Health Disparities; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Minority Health & Health Disparities (NIMHD) National Heart, Lung, and Blood Institute (NHLBI); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) N01HC095162 / DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) P30DK063491 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) 1406712 / NSF DMS; National Science Foundation (NSF) R21ES020811 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Urban Health Collaborative
- Web of Science ID
- WOS:000361527000005
- Scopus ID
- 2-s2.0-84941732003
- Other Identifier
- 991019169652004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biology
- Mathematical & Computational Biology
- Statistics & Probability