Potential nonresponse bias in a clinical examination after initial screening using iron phenotyping and HFE genotyping in the hemochromatosis and iron overload screening study.
BACKGROUND
Little is known about the factors affecting participation in clinical assessments after HEmochromatosis and IRon Overload Screening.


METHODS
Initial screening of 101,168 primary care patients in the HEmochromatosis and IRon Overload Screening study was performed using serum iron measures and hemochromatosis gene (HFE) genotyping. Using iron phenotypes and HFE genotypes, we identified 2256 cases and 1232 controls eligible to participate in a clinical examination. To assess the potential for nonresponse bias, we compared the sociodemographic, health status, and attitudinal characteristics of participants and nonparticipants using adjusted odds ratios (ORs) and 95% confidence interval (CI).


RESULTS
Overall participation was 74% in cases and 52% in controls; in both groups, participation was highest at a health maintenance organization and lowest among those under 45 years of age (cases: OR = 0.68; 95% CI 0.53, 0.87; controls: OR = 0.59; 95% CI 0.44, 0.78). In controls only, participation was also lower among those over 65 years of age than the reference group aged 46-64 (OR = 0.64; 95% CI 0.47, 0.88). Among cases, participation was higher in HFE C282Y homozygotes (OR = 3.98; 95% CI 2.60, 6.09), H63D homozygotes (OR = 2.79; 95% CI 1.23, 6.32), and C282Y/H63D compound heterozygotes (OR = 1.82; 95% CI 1.03, 3.22) than in other genotypes, and lower among non-Caucasians and those who preferred a non-English language than in Caucasians and those who preferred English (p < 0.0001).


CONCLUSIONS
Subjects with greatest risk to have iron overload (C282Y homozygotes; cases > or =45 years; Caucasians) were more likely to participate in a postscreening clinical examination than other subjects. We detected no evidence of strong selection bias.
Speechley
Mark
M
Department of Epidemiology & Biostatistics, University of Western Ontario, London, Canada. speechly@uwo.ca
Barton
James C
JC
Passmore
Leah
L
Harrison
Helen
H
Reboussin
David M
DM
Harris
Emily L
EL
Rivers
Charles A
CA
Fadojutimi-Akinsiku
Margaret
M
Wenzel
Lari
L
Diaz
Sharmin
S
D015982:Bias; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D007501:Iron