The confounding effect of cryptic relatedness for environmental risks of systolic blood pressure on cohort studies.
The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated the confounding effect of unadjusted CR among a rural cohort in the relationship between environmental risk factors (body mass index, smoking status, alcohol consumption) and systolic blood pressure. We applied the methods of population-based whole-genome association studies for the analysis of the genome-wide single nucleotide polymorphism data in 1622 subjects, and detected 20.2% CR in this cohort population. In the case of the sample size, approximately 1000, the ratio of CR to the population was 20.2%, the population prevalence 25%, the prevalence in the CR 26%, heritability for liability 14.3% and prevalence in the subpopulation without CR 26%, the difference of estimated regression coefficient between samples with and without CR was not significant (P-value = 0.55). On the other hand, in another case with approximately >20% heritability for liability, we showed that confounding due to CR biased the estimation of exposure effects.
Advanced Molecular Epidemiology Research Institute (AMERI), Cohort Management Unit, Yamagata University Yamagata, Japan.
Kyoko
K
Shibata
Division of Personalized Prevention and Epidemiology, Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University Sendai, Japan.
Atsushi
A
Hozawa
AMERI, Genomic Information Analysis Unit, Yamagata University Yamagata, Japan.
Gen
G
Tamiya
AMERI, Genomic Information Analysis Unit, Yamagata University Yamagata, Japan.
Masao
M
Ueki
AMERI, Genomic Information Analysis Unit, Yamagata University Yamagata, Japan.
Tomohiro
T
Nakamura
AMERI, Cohort Management Unit, Yamagata University Yamagata, Japan.
Hiroto
H
Narimatsu
AMERI, Respiratory and Cardiovascular Diseases Research Center, Yamagata University Yamagata, Japan ; Department of Cardiology, Pulmonology, and Nephrology, Yamagata University Yamagata, Japan.
Isao
I
Kubota
Department of Gastroenterology, Yamagata University Yamagata, Japan.
Yoshiyuki
Y
Ueno
AMERI, Metabolic and Degenerative Diseases Research Center, Yamagata University Yamagata, Japan ; Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Yamagata, Japan.
Takeo
T
Kato
Department of Ophthalmology, Yamagata University Yamagata, Japan.
Hidetoshi
H
Yamashita
AMERI, Genomic Information Analysis Unit, Yamagata University Yamagata, Japan ; AMERI, Cohort Management Unit, Yamagata University Yamagata, Japan.
Akira
A
Fukao
Graduate School of Medicine, Department of Neurosurgery, Yamagata University Yamagata, Japan.
Takamasa
T
Kayama
confounding effect; cryptic relatedness; systolic blood pressure