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Cryptic relatedness in epidemiologic collections accessed for genetic association studies: experiences from the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study and the National Health and Nutrition Examination Surveys (NHANES).

ABSTRACT: Epidemiologic collections have been a major resource for genotype-phenotype studies of complex disease given their large sample size, racial/ethnic diversity, and breadth and depth of phenotypes, traits, and exposures. A major disadvantage of these collections is they often survey households and communities without collecting extensive pedigree data. Failure to account for substantial relatedness can lead to inflated estimates and spurious associations. To examine the extent of cryptic relatedness in an epidemiologic collection, we as the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study accessed the National Health and Nutrition Examination Surveys (NHANES) linked to DNA samples ("Genetic NHANES") from NHANES III and NHANES 1999-2002. NHANES are population-based cross-sectional surveys conducted by the National Center for Health Statistics at the Centers for Disease Control and Prevention. Genome-wide genetic data is not yet available in NHANES, and current data use agreements prohibit the generation of GWAS-level data in NHANES samples due issues in maintaining confidentiality among other ethical concerns. To date, only hundreds of single nucleotide polymorphisms (SNPs) genotyped in a variety of candidate genes are available for analysis in NHANES. We performed identity-by-descent (IBD) estimates in three self-identified subpopulations of Genetic NHANES (non-Hispanic white, non- Hispanic black, and Mexican American) using PLINK software to identify potential familial relationships from presumed unrelated subjects. We then compared the PLINKidentified relationships to those identified by an alternative method implemented in Kinship-based INference for Genome-wide association studies (KING). Overall, both methods identified familial relationships in NHANES III and NHANES 1999-2002 for all three subpopulations, but little concordance was observed between the two methods due in major part to the limited SNP data available in Genetic NHANES. Despite the lack of genome-wide data, our results suggest the presence of cryptic relatedness in this epidemiologic collection and highlight the limitations of restricted datasets such as NHANES in the context of modern day genetic epidemiology studies.

SUBMITTER: Malinowski J

PROVIDER: S-EPMC4620157 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Cryptic relatedness in epidemiologic collections accessed for genetic association studies: experiences from the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study and the National Health and Nutrition Examination Surveys (NHANES).

Malinowski Jennifer J Goodloe Robert R Brown-Gentry Kristin K Crawford Dana C DC

Frontiers in genetics 20151026

Epidemiologic collections have been a major resource for genotype-phenotype studies of complex disease given their large sample size, racial/ethnic diversity, and breadth and depth of phenotypes, traits, and exposures. A major disadvantage of these collections is they often survey households and communities without collecting extensive pedigree data. Failure to account for substantial relatedness can lead to inflated estimates and spurious associations. To examine the extent of cryptic relatedne ...[more]

PMID: 26579192

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Project description:Prevalence and factors associated with obstructive and restrictive lung function in people with chronic kidney disease (CKD) are unknown.Cross-sectional and longitudinal analyses.Participants aged 40 to 79 years from NHANES (National Health and Nutrition Examination Survey) 2007 to 2012 who underwent spirometry testing.CKD (estimated glomerular filtration rate [eGFR] >15-<60mL/min/1.73m(2) or urinary albumin-creatinine ratio ? 30mg/g).Restrictive lung function (defined as FEV1/FVC?0.70 and baseline FVC<80% predicted), obstructive lung function (defined as FEV1/FVC<0.70 based on postbronchodilator spirometric results), and mortality data (available for 2007-2008 and 2009-2010 survey periods).7,610 participants (CKD=1,338; non-CKD=6,272) were included. Prevalences of obstructive lung function adjusted to the mean age of 55 years and 50% men in the CKD and non-CKD groups were 15.6% and 13.3%, respectively (P=0.2). Similarly, adjusted prevalences of restrictive lung function in the CKD and non-CKD groups were 9.8% and 6.7%, respectively (P=0.01). Presence of albumin-creatinine ratio ? 30mg/g was associated with obstructive (OR, 1.42; 95% CI, 1.07-1.88) and restrictive lung function (OR, 1.43; 95% CI, 1.01-2.03) in the entire study cohort. eGFR<60mL/min/1.73m(2) was associated with higher odds of obstructive lung function. In a multivariable Cox model, age (HR, 1.07; 95% CI, 1.04-1.11) and presence of obstructive lung function (HR, 2.68; 95% CI, 1.80-3.97), but not CKD measures, were associated with death.Small proportion of participants with advanced kidney disease.In a representative sample of US adults, impaired lung function is common in those with and without CKD. Albuminuria was independently associated with both obstructive and restrictive lung function, and eGFR<60mL/min/1.73m(2) was associated with higher odds of obstructive lung function. Older age and obstructive lung function were associated with higher likelihood of death. Further studies examining the burden of lung disease in advanced CKD are needed.

Dataset Information

Cryptic relatedness in epidemiologic collections accessed for genetic association studies: experiences from the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study and the National Health and Nutrition Examination Surveys (NHANES).

Publications

Cryptic relatedness in epidemiologic collections accessed for genetic association studies: experiences from the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study and the National Health and Nutrition Examination Surveys (NHANES).

Similar Datasets

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