English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the zaia usage as premium feature

ZAIA

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the access of premium content as premium feature

Premium Content

Zendy Tools

Zendy Open

By definition, complex traits such as obesity and its comorbidities result from complex origins. At the very least these include genetic, environmental and behavioral causes and their interactions. Epidemiologicalbased studies have identified some well-known, replicated, environmental and genetic risk factors for complex diseases. However, at the population level, investigations have tended to focus on a single cause, rarely combining a multidisciplinary approach. Regarding genetics, genome-wide association studies (GWAS) have been one tool that genetic epidemiologists have used to identify genetic variation contributing to disease risk. GWAS have tended to be criticized for identifying associated markers but not functional mutations, for potentially missing important genetic variation by overlookingminorities, and especially for explaining only a small proportion of the heritability of a trait. However, GWAS are designed to be somewhat hypothesisgenerating, and despite the criticisms, many associations identified to date provide leads for additional studies (Sainani, 2014). Onewell-studied and replicated set of GWAS results focuses on the region of chromosome 9 (9p21.3) which encodes cell cycle-regulating products of the cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) locus, including the long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus). This locus has been associated with many diseases including coronary artery disease, atherosclerosis, type 2 diabetes and cancer. However, despite extensive studies to date, it is not clear how this locus acts to impact disease (Hannou et al., 2015), nor how behavior and environment might mitigate these effects. Epidemiologists have also investigated behavioral and environmental influences such as nutrition on development of disease. Dr. David Barker was one of the first investigators to report an observed link between prenatal undernutrition and later heart disease, hypothesizing that it resulted from an affluent diet as an adult (Barker and Osmond, 1986). Since his initial study, there has been additional investigation and debate surrounding this hypothesized link, leading to a continuing refinement of a fetal origins of adult diseases hypothesis. Notwithstanding, the evidence is overwhelming that prenatal exposures can impact adult traits. The biological mechanisms underlying these populationlevel associations have yet to be determined. One suggestion supported by experimental evidence is that epigenetic mechanisms might translate early life exposures into changes, such as altered gene expression, that persist throughout the life course, and possibly beyond to future

Epigenetic Studies of Perinatal Determinants of Later Obesity Link Important, but Previously Unrelated, Genetic and Epidemiological Findings