title: Assessing age-related etiologic heterogeneity in the onset of islet autoimmunity.
abstract: Type 1 diabetes (T1D), a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA) where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY) has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW) ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA) levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases.
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Brittni N
authors.initials: BN
authors.lastname: Frederiksen
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Miranda
authors.identifier: 0000-0002-3840-3660
authors.initials: M
authors.lastname: Kroehl
authors.affiliation: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Barón
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Lamb
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Crume
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Marci K
authors.initials: MK
authors.lastname: Sontag
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 1775 Aurora Ct., Aurora, CO 80045, USA.
authors.forename: Marian
authors.identifier: 0000-0003-3829-9207
authors.initials: M
authors.lastname: Rewers
authors.affiliation: Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
mesh_terms: D000367:Age Factors; D017668:Age of Onset; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D015525:Fatty Acids, Omega-3