OR51-4 Genes Associated with Obesity in Adulthood Are Associated with Newborn Birth Weight and Adiposity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR51-Obesity: From Genes to Populations
Translational
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 10:00 AM
Room 303 (Moscone Center)
Reeti Chawla*1, Loren Lynette Armstrong2, M. Geoffrey Hayes2 and William L. Lowe Jr.*2
1Ann and Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL, 2Feinberg School of Medicine, Northwestern University, Chicago, IL
The developmental origins of health and disease model postulates that the intrauterine environment influences birth weight and later obesity; however birth weight and adult obesity may also share a common genetic background. Genome wide association studies have identified numerous obesity susceptibility loci in adults, but the impact of these genes on newborn size is not well established. To test our hypothesis that adult obesity genes impact newborn adiposity, we assessed whether neonatal single nucleotide polymorphisms (SNPs) in adult obesity genes are associated with birth weight (BW) and sum of skin folds (SS) among newborns from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study, an epidemiologic study which examined associations of glucose tolerance during pregnancy and risk of adverse pregnancy outcomes.  SNPs in 40 gene regions previously showing genome wide associations with adult BMI (body mass index) or waist to hip ratio were identified. After controlling for maternal BMI, height, blood pressure, smoking, and alcohol use, genotyped and imputed SNPs were tested for associations with BW and SS from 4465 HAPO newborns [1053 Afro-Caribbean (AC), 1351 European (EU), 866 Mexican American (MA) and 1195 Thai (TH)].  After trimming for ancestry specific linkage disequilibrium (r2>0.8), 26 ancestry-specific SNPs were associated with newborn BW or SS (p <0.001). Among AC, 5 SNPs in 4 genes (PRKD1, SLC39A8, LRP1B, PTBP2) were associated with BW, and 6 SNPs in 4 gene regions (ZNRF3, LRP1B, MAP2K5, LY86) were associated with SS. Among EU, 3 SNPs in 2 gene regions (ZNRF3, LRP1B) were associated with BW, and 4 SNPs in 3 genes (GTF3A, NRXN3, FTO) were associated with SS. Among MA, rs7517677 in TNN13K was associated with SS, and 5 SNPs in 5 gene regions (LRP1B, DGKG, LRRN6C, NEGR1, SLC39A8) were associated with BW.  SNPs in LRP1B encoding LDL receptor-related protein 1B were associated with BW among EU, AC and MA, and SS among AC and TH. Meta-analysis across all ancestries identified 3 SNPs associated with newborn BW (p<0.001): rs11627494 in PRKD1 encoding protein kinase D1 which regulates insulin secretion, rs2286442 near ZNRF3 encoding zinc and ring finger 3 protein involved in regulating the Wnt signaling pathway, and rs3900513 in TNN13K encoding a cardiac specific MAP kinase.  These data demonstrate that unique ancestry-specific SNPs in gene regions known to be associated with adult BMI are also associated with newborn birth weight or adiposity among a large multiethnic cohort of newborns. Preliminary results suggest that combinations of these SNPs may also predict size and adiposity at birth by means of an ancestry-specific genetic risk score. These findings also suggest some similarities in the genetic underpinnings of newborn and adult adiposity, and may be useful in identifying newborns at later risk of obesity.

Nothing to Disclose: RC, LLA, MGH, WLL Jr.

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