The interaction between physical activity and obesity gene variants in association with BMI: Does the obesogenic environment matter?
Introduction
Adolescence is a high-risk period for weight gain that is often maintained or exacerbated into adulthood (Gordon-Larsen and Adair, 2004, The and Suchindran, 2010). Physical activity (PA) is an effective behavior to prevent or reduce unwanted weight gain (Knowler and Barrett-Connor, 2002, Singh and Mulder, 2008, Hankinson and Daviglus, 2010). A growing literature suggests that neighborhood amenities, such as physical activity resources, green-space, as well as neighborhood socio-demographics are associated with the physical activity of residents (Block and Scribner, 2004, Boone-Heinonen and Gordon-Larsen, 2011a, Boone-Heinonen and Gordon-Larsen, 2011b, Cummins and Stafford, 2005, Frank and Sallis, 2006, Gordon-Larsen and Nelson, 2006, Larson and Story, 2009, Moore and Diez Roux, 2006, Oakes and Forsyth, 2007, Rodriguez and Evenson, 2009). However, while the physical activity literature has included attention to neighborhood environment, few studies have examined gene by physical activity interactions and obesity in relation to obesogenic neighborhood factors.
Several genetic loci that influence body mass index (BMI) or obesity have been successfully identified primarily in European descent adults (Speliotes et al., 2010; Locke et al., 2015), but many generalize to other ethnic groups (Wen and Cho, 2012, Graff and Fernandez-Rhodes, 2013, Monda and Chen, 2013). Further, recent studies suggest that physical activity may modify a genetic susceptibility to obesity by attenuating the genetic effect on BMI (Andreasen and Stender-Petersen, 2008, Sonestedt and Roos, 2009, Kilpelainen and Qi, 2011). The most notable study reported a weaker genetic effect on BMI from the FTO locus in more active compared to inactive individuals (Kilpelainen and Qi, 2011, Xi and Wang, 2011). Previously we examined the interaction of established obesity susceptibility SNPs with <5 vs.≥5 bouts moderate to vigorous physical activity (MVPA) per week in relation to BMI-for-age Z-scores in a nationally representative sample of European American (EA), African–American (AA) and Hispanic American (HA) adolescents (Richardson et al., 2014). We reported that higher moderate to vigorous physical activity (MVPA) per week attenuated the effect on BMI-for-age Z-score of variants in/near GNPDA2 and FTO in EA, in/near MAP2K5, LMX1B, and NRXN3 in AA, and in/near LZTR2 and LRRN6C in HA. Thus, we demonstrated a protective effect of MVPA on increased genetic susceptibility to obesity. However, the interaction between genetic variants and physical activity behaviors in relation to obesity has not previously accounted for the neighborhood environment. While it has been shown that the obesogenic environment is associated with obesity through decreased physical activity, it is not known how this can influence the PA-SNP interaction on obesity.
To address this gap in the literature, we used data from a US nationally representative, longitudinal cohort to determine whether established obesity SNPs interact with MVPA in relation to BMI-for-age Z score, once accounting for obesogenic neighborhood factors. We hypothesized that the interaction between obesity SNPs and MVPA in relation to BMI-for-age Z score inverse association would be influenced by accounting for neighborhood obesogenic features. In the current analysis, we selected SNPs from 39 obesity susceptibility SNPs that were found to have an interaction with MVPA that met suggestive statistical significance at p-value<0.10 using the current sample and based on the analyses previously performed (Richardson et al., 2014) and further tested for the independence of these interaction effects once adjusting for neighborhood environment elements, such as crime, population density, green space, physical activity resources, and neighborhood sociodemographics.
Section snippets
Add Health
Participants. Add Health is a nationally representative cohort of adolescents (1994-95, n=20,745, aged 11–20 y, mean age 15.9 y) drawn from a probability sample of 80 US high schools and 52 US middle schools, representative of US schools in 1994–95 with respect to region, urban setting, school size, school type, and race or ethnic background. Wave II (1996, n=14,738, aged 12–21 y, mean age 16.5 y) included by design Wave I adolescents still of school-age, including those currently in high school
Results
The Add Health adolescents were on average 16.4 years of age (ages 12–21 y, 47.5% male) and had a mean BMI-for-age Z-score of 0.38 (Table 1), ranging from 0.31 in EA to 0.58 in AA. Approximately 60% of adolescents reported MVPA≥5 bouts per week. Counts of pay physical activity facilities were higher in EA neighborhoods but parks were higher among AA and HA neighborhoods. Infrastructure appeared similar across race/ethnicity, but the counts of cul-de-sacs were highest (mean 5.4) in HA
Acknowledgements
This work was funded by National Institutes of Health Grant R01HD057194. P.G.L., K.E.N., E.M.L., L.A.L, A.S.R, K.L.Y., and M.G. contributed to study design, A.S.R. and M.G. performed the data analysis, and P.G.L., K.E.N., A.Y.L., E.M.L., L.A.L, K.M.H., K.L.Y., and M.G. contributed to writing the manuscript, all other authors provided critical evaluation of the manuscript. A.S.R, K.L.Y., M.G., K.E.N., and P.G.L. had full access to all the data in the study and take responsibility for the
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