O-1i Pre- And Postnatal Feeding – Mechanisms in Animal Models. Sherin Devaskar. Invited Speaker, USA. O-1i-1 Postnatal Growth Is Associated with DNA Methylation and Childhood Adiposity: Using Genetic Variation to Infer the Direction of Causation. Alix Groom 1 , Kate Potter 1 , Valerie Turcot 2 , Mark S. Pearce 3 , Nicholas D. Embleton 4 , Caroline L. Relton 1 . 1 Institute of Genetic Medicine, Newcastle University, United Kingdom; 2 Institute of Nutraceuticals and Functional Foods, Université Laval, Canada; 3 Institute of Health and Society, Newcastle University, United Kingdom; 4 Neonatal Service, Royal Victoria Infrmary, Newcastle upon Tyne, United Kingdom. The role of epigenetic mechanisms in the developmental programming of cardiometabolic disease is the focus of considerable interest. Epigenetic epidemiological studies of human populations can contribute to the evidence base in this feld however reverse causation (where a disease state might perturb epigenetic patterns) might explain observed associations. Genetic variation, in the form of single nucleotide polymorphisms (SNPs), is robust to reverse causation as a disease state cannot alter genotype and can be used to infer the direction of causality. Following gene expression analysis the TACSDT2 gene was identifed as a mediator of altered childhood adiposity in children aged 9-13 years experiencing rapid postnatal growth in the Newcastle Preterm Birth Growth Study. DNA methylation analysis of seven promoter CpG sites and genotyping of a promoter SNP (rs61779296) in the TACSTD2 gene was undertaken in groups of 94 and 122 individuals, respectively using Pyrosequencing analysis. Percentage methylation demonstrated associations with postnatal growth (Mann Whitney: U = -2.40, p = 0.016); TACSTD2 gene expression (Spearman’s rank correlation: rho = -0.55, p = 0.016); and childhood fat mass (Spearman’s rank correlation: rho = -0.22, p = 0.037). rs61779296 genotype was strongly associated with TACSTD2 methylation and expression levels (Kruskal Wallis: c 2 = 9.65, p = 0.008; c 2 = 48.47, p < 0.001 , respectively); and childhood fat mass (Kruskal Wallis: c 2 = 8.48, p = 0.014); but not postnatal growth (c 2 =0.67, p = 0.723). Similar fndings were demonstrated between genetic markers and percentage fat mass. The association of methylation and adiposity at age 9-13 years could plausibly arise through reverse causation. However, the clear association of TACSTD2 genotype (in strong linkage disequilibrium with the promoter methylation) with adiposity suggests that this is not the case. Lack of correlation between postnatal growth and genotype indicate that these two factors act independently to modulate TACSTD2 methylation, expression and subsequent adiposity. O-1i-2 Exclusive Breast Feeding in Infancy Has a Protective Effect on Development of Knee Osteophytes: The Newcastle Thousand Families Study. Ajay Abraham 1 , Kay D. Mann 1 , Mark S. Pearce 1 , Roger M. Francis 3 , Fraser Birrell 2 . 1 Institute of Health & Society, Newcastle University, United Kingdom; 2 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, United Kingdom; 3 Institute for Ageing & Health, Newcastle University, United Kingdom. There has been very little lifecourse research looking at the risk of osteoarthritis (OA). Several studies have demonstrated the association between adult risk factors such as obesity and higher bone mineral density with subsequent knee OA. We performed a lifecourse analysis of risk factors for knee OA (defned by osteophytes on ultrasound) acting at different stages of life, including early life factors, among members of the Newcastle Thousand Families birth cohort. Potential risk factors for knee osteoarthritis (including birth weight, breast feeding data and socioeconomic status) have been collected prospectively in this birth cohort of subjects aged 63 (born in May-June 1947) and an a priori conceptual framework was developed. Subjects had both knees scanned by a trained musculoskeletal sonographer. Ultrasound protocols were derived from European League Against Rheumatism (EULAR) guidelines. The presence of knee osteophytes was assessed at the tibial and femoral sites, medially and laterally. These data were analysed in relation to a range of factors from across the lifecourse using logistic regression models. Among the 311 participants, the prevalence of knee osteophytes was 22%, 25% and 30% for right, left and “any” knee, respectively. While birth weight, exclusive breast feeding and social class at birth showed signifcant univariate associations with knee osteophytes, only exclusive breast feeding (among factors acting in early life) showed a signifcant association in the adjusted model (OR 0.81 per month; CI 0.68, 0.97; p=0.02). BMI (OR 1.11; CI 1.02, 1.20; p=0.01) and total hip bone mineral density at age 50 (OR 1.37 per 0.1 g/cm 2 ; CI 1.06, 1.78; p=0.02) were the factors acting in adulthood that increased the risk of knee osteophytes at age 63. This is the frst study to perform a lifecourse analysis of knee OA risk using prospectively collected data. While exclusive breast feeding is known to decrease risk of adult obesity and therefore of knee OA, this study suggests that exclusive breast feeding is an independent predictor of knee OA. The mechanism might be reduced burden of infection and infammation through the lifecourse, a testable hypothesis. O-1i-3 Age-Specifc Effects of Faster Linear Growth and Faster Relative Weight Gain: A Comparison across Multiple Cardiometabolic Disease Risk Factors. Nanette R. Lee 1 , Isabelita Bas 1 , Linda S. Adair 2 . 1 USC Offce of Population Studies Foundation, University of San Carlos, Cebu, Philippines; 2 Department of Nutrition, University of North Carolina at Chapel Hill, NC, USA. There is concern that faster infant weight gain increases later risk of cardiometabolic diseases. However, the importance of linear growth in comparison to weight gain at different ages has not been well studied. We aimed to determine how faster length and weight gain from birth to age 21 y relate to young adult body composition, blood pressure, fasting glucose and insulin, and lipid profles (high and low density lipoprotein cholesterol and triglycerides). We used data from the Cebu Longitudinal Health and Nutrition Survey, a community-based longitudinal study in the Philippines. Conditional weight and length measures (residuals derived from regressing size measures at each age on all prior measures) were used to represent faster linear growth and faster relative weight gain (greater than expected weight in relation to linear growth) from 0-6, 6-12, 12-24 months, then from 2 to 8, 8-11, 11-15 and 15-21 y. Young adult risk factors were regressed on the conditional growth measures, adjusting for adult age in sex-stratifed models and effect sizes for each interval were compared across outcomes (n=1432). Chronic disease risks related to faster relative weight gain in infancy were quite small relative to effects of faster gain from later childhood to adulthood. For example, faster linear growth and weight gain prior to adolescence were not signifcantly related to adult HDL, LDL or triglycerides levels. Faster relative weight gain, but not linear growth after age 15 was associated with higher blood pressure, higher levels of LDL and triglycerides and increased insulin resistance. These increased risks refect body composition, since faster adolescent weight gain strongly associates with higher adult fat mass. Faster linear growth in early infancy signifcantly predicted higher young adult lean mass. Patterns were similar for males and females. Results suggest that benefts of promoting early growth in low and middle income settings outweigh the modest elevation in chronic disease risk. Further, opportunities for intervention to prevent adult chronic disease risk include the late-childhood to adolescent period. O-1i-4 DNA Methylation of Promoter Regions of Insulin like Growth Factor 2 Is Associated with Childhood Head Circumference. Rae-Chi Huang 1 , Lawrence J. Beilin 1 , Anke Van Eckelen 2 , Craig Pennell 1 , Jeff Craig 3 . 1 University of Western Australia, WA, Australia; 2 Telethon Institute for Child Health Research, WA, Australia; 3 Murdoch Children’s Research Institute, Vic, Australia. Some evidence suggests that decreased adiposity at birth directs nutrition towards head growth. We hypothesize that the mechanism (at least in part) is due to altered methylation of insulin like growth factors.Our aim is to investigate the relationship between DNA methyation of Insulin like Growth factor 1 and 2 (IGF1 and IGF2/H19) promoter regions with anthropometry from birth to age 17 years. Journal of Developmental Origins of Health and Disease (2011), Volume 2, Supplement 1, S2-S34 © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011 doi:10.1017/S204017441100047X