Such processes may explain some of the missing heritability for conditions that repeat across generations. Environmental exposures, including chemical toxicants, psychosocial stressors, behaviors, and nutrition, are all potentially important influences that may impact health outcomes directly or via interactions with the genome. That is, genetic variants have often explained a small fraction of the overall heritability of these diseases and their effect sizes are small. While many successes in large-scale human genetic studies exist, there remains a substantial amount of missing heritability in complex childhood disorders. Heritability of health and disease risk in humans and other species involves influences beyond the genetic code. Both maternal and paternal exposures and transmission patterns are considered, with attention paid to the attendant ethical, legal and social implications. This review highlights the current epidemiologic literature and supporting animal studies that describe intergenerational and transgenerational health effects of environmental exposures. One putative mechanism for these environmental health effects is via altered epigenetic regulation. Mounting evidence, primarily in animals, suggests environmental exposures may generate or perpetuate altered health outcomes across one or more generations. While there have been clear successes in large-scale human genetic studies in recent decades, there is still a substantial amount of missing heritability to be elucidated for complex childhood disorders. Environmental exposures, psychosocial stressors and nutrition are all potentially important influences that may impact health outcomes directly or via interactions with the genome or epigenome over generations.
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