Trend tests for genetic association using population-based cross-sectional complex survey data

Department of Statistics, The George Washington University, Washington, DC 20052, USA.
Biostatistics (Impact Factor: 2.65). 10/2009; 11(1):48-56. DOI: 10.1093/biostatistics/kxp035
Source: PubMed


Genetic data collected from surveys such as the Third National Health and Nutrition Examination Survey (NHANES III) enable
researchers to investigate the association between wide varieties of health factors and genetic variation for the US population.
Tests for trend in disease with increasing number of alleles have been developed for simple random samples. However, surveys
such as the NHANES III have complex sample designs involving multistage cluster sampling and sample weighting. These types
of sample designs can affect Type I error and power properties of statistical tests based on simple random samples. In order
to address these issues, we have derived tests of trend based on Wald and quasi-score statistics, with and without assuming
a genetic model, that account for the complex sampling design. The finite-sample properties of the proposed test procedures
are evaluated via Monte Carlo simulation studies. We make recommendations about the choice of the test statistic depending
on whether or not the underlying genetic model is known. Proposed test statistics are applied to NHANES III data to test for
associations between the locus ADRB2 (rs1042713) and obesity, between VDR (rs2239185) and high blood lead level, and between
TGFB1 (rs1982073) and asthma.

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