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Food or drugs as medicine? Genetic atlas of influences on metabolites

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Notice how may studies of genes are linked to being targeted in drug-development programs as compared to using food as medicine to tailor your food or supplements, plant extracts, or vitamins and minerals to your genes or at least to the way your body responds chemically, metabolically, and genetically to diets or types of food, or even unprocessed versus processed foods. Have you ever wondered whether your genes influence where you live, how much money you earn, the environment you can afford or choose to inhabit, whether you drive or use public transportation, and what foods you choose that are available--all leading to your health status and longevity prospects?

What also impacts your health is whether you live in a county where most people are healthier than most people in another county, for example, here in Sacramento, those living in Placer County appear in statistics records to be healthier and live longer than those who live in neighboring Yuba County, according to the May 11, Sacramento Bee article by Daniel Weintraub, "The Conversation: Stark differences widen health gap." That article notes that the disparities in health outcomes are linked to a combination of other factors that often move in tandem with wealth: employment, education, housing, transportation, access to healthy food and outdoor exercise, and leisure time. Air pollution also may play a part.

You have more technology firms in Placer than in Yuba. Median household income in Yuba County is about $41,000, compared to $69,000 in Placer County. So where you live in the Sacramento and nearby regional areas has a lot to do with what foods you eat and what you do for a living and for leisure. But what about genes? Do people with different genes live in different places linked to their genes, metabolism, and food security status? Do your genes have any influence on where you live, and where you live influence your health. And is what you eat tailored to your genes? Meanwhile, as you ponder these questions, scientists are looking for genes to target in drug-development programs.

Children's avoidance of food may be genetic, but also could be influenced by environment, says the abstract of a recent study, "Genetic and environmental influences on children's food neophobia." Food neophobia in children has been associated with a low intake of fruit, vegetables, and protein foods. As such kids grow up, they may still insist that they don't like to eat vegetables or fruit, and their own children may act the same way if they've inherited that trait or if the environment showed them that family members didn't eat certain foods, usually vegetables and fruits. But avoidance of foods also could focus on animal protein, dairy, or any food or food style, such as certain spices, salty foods, herbs, or flavors. The definition of avoidance of certain foods is called neophobia.

The design of effective interventions to improve children's diets would be facilitated by a better understanding of the determinants of neophobia, says that August 2007 study, "Genetic and environmental influences on children's food neophobia1,2,3." Researchers found that Neophobia appears to be a heritable trait, but almost a quarter of the phenotypic variation is accounted for by nonshared environmental factors. An important aim for future research is the identification of influential aspects of the environment specific to individual children, according to the study, "Genetic and environmental influences on children's food neophobia1,2,3," published in the American Journal of Clinical Nutrition.

Now let's move to the subject of an atlas of genetic influences on human blood metabolites

On one hand there's a goal to facilitate drug discovery for metabolic disorders and also help researchers to understand the biology behind disease. And on the other hand, the studies are fewer using foods to help certain metabolic disorders that actually would respond to changes in food. For example, a person with an adverse reaction to cereal grains might change the type of food selected to change the metabolic reaction to food.

An example might be to drink clean water instead of soda with each meal, or have a healthier snack instead of processed or deep-fried foods or various sweets and salty chips. People are concerned whether genes or foods have more or fewer effects on an individual's metabolism. After all with the genetic variation between peoples, what's healthy food for some people disturbs another person's metabolism. And regarding genes, their influence on human blood metabolites helps health care professionals and anyone else to understand how genes affect metabolism.

A new atlas shows how genes affect our metabolism

A new atlas named, "An atlas of genetic influences on human blood metabolites," recently published in Nature Genetics shows how genes affect our metabolism. It's an atlas of molecules that paves the way for improved understanding of metabolic diseases. In the most comprehensive exploration of the association between genetic variation and human metabolism, researchers have provided unprecedented insights into how genetic variants influence complex disease and drug response through metabolic pathways. Authors are Shin S-Y et al (2014).

A comprehensive study of associations between genetic variation and human metabolism will improve our understanding of the molecular pathways underlying common complex diseases such as hypertension, cardiovascular disease and diabetes. Researchers at the Wellcome Trust Sanger Institute have linked 145 genetic regions with more than 400 molecules involved in human metabolism (in human blood).

This atlas of genetic associations with metabolism provides many new opportunities to understand the molecular pathways underlying associations with common, complex diseases. Metabolic molecules, known as metabolites, include a wide range of different molecules such as vitamins, lipids, carbohydrates and nucleotides.

The atlas is a useful tool for mapping the associations between genetic regions and metabolite levels

They make up parts of, or are the products of, all biological pathways. This new compendium of associations between genetic regions and metabolite levels provides a powerful tool to identify genes that could be used in drug and diagnostic tests for a wide range of metabolic disorders.

"The sheer wealth of biological information we have uncovered is extraordinary," says Dr Nicole Soranzo, according to the May 11, 2014 news release, "Atlas shows how genes affect our metabolism." Soranzo is the senior author from the Wellcome Trust Sanger Institute. "It's exciting to think that researchers can now take this freely available information forward to better understand the molecular underpinnings of a vast range of metabolic associations."

The team measured the levels of a large number of metabolites, both those already known and many as yet uncharacterized, from many different metabolic pathways

They found 90 new genetic associations, trebling the figure of known genetic associations with metabolites. In many of the cases where metabolites were known, the team were able to link the molecule to gene function. They mapped genes to their likely substrates or products and linked these to a number of conditions, including hypertension, cardiovascular disease and diabetes.

They further found that these genetic regions map preferentially to genes that are currently targeted in drug-development programs. This provides new opportunities to assess genetic influences on drug response, and to assess the potential for existing drugs to treat a wide range of diseases.

Genes are currently targeted in drug-development programs

"We developed an open-access database that allows researchers to easily search through the findings, to understand genetic variants associated with metabolism one metabolite at a time and in the context of the complete metabolic network," says Dr Gabi Kastenmüller, according to the news release. Kastenmüller is co-senior author from the Helmholtz Center Munich, Germany. "This database will facilitate drug discovery for metabolic disorders and also help researchers to understand the biology behind disease."

Other associations suggest tantalising possibilities for further study. For instance, a number of the genetic associations identified involved aromatic acids, such as tryptophan, which are important for brain function. While this study did not measure association of metabolites in the brain, these genetic findings open new avenues to assess potential genetic influences on brain function and responses to drugs that affect brain function, such as antidepressants.

"This work provides an important new window into the genetic variation underlying human metabolism," said Dr Eric Fauman, study co-author and Associate Research Fellow from Pfizer Inc. "Through targeted Precision Medicine and by linking human disease genes to in vivo biological markers, we hope to enhance our ability to deliver impactful new medicines for patients across a variety of disorders."

You also may be interested in the abstracts of some other studies by different researchers, appearing in Nature Genetics , such as: "Low copy number of the salivary amylase gene predisposes to obesity." Or see, "Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility." You also may wish to see the website of the Wellcome Trust Sanger Institute.

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