Can sequencing the human genome help guide individual dietary choices? Private companies now offer consumers the opportunity to have their genes sequenced and use the information for multiple interesting purposes: discovering their ancestral ethnic or geographic origins, finding distant relatives, and, most relevant to health and nutrition, determining whether they have increased susceptibility to various diseases. This opens a fascinating new world of treating or potentially preventing various illnesses, but the science of this is in its infancy, and overzealous claims should be interpreted with caution.

There’s no doubt that certain genetic factors either outright cause certain conditions or influence susceptibility to them. There’s a difference, however, between conditions that are entirely genetic in origin (for example, sickle cell anemia) and those that are epigenetic. Take Alzheimer’s disease (AD), for example. The ε4 allele of the ApoE gene (ApoE4) is the strongest known genetic risk factor for this condition, but by itself, this gene is neither required nor sufficient to cause Alzheimer’s. Millions of people living with AD do not have even one copy of this gene, let alone two, and not everyone who’s homozygous for ApoE4 develops Alzheimer’s. Research indicates that the increased susceptibility among people with this gene is not a result of the gene, per se, but rather, the interaction of this gene with dietary and environmental factors it is not well-suited for.

Turning to a different neurodegenerative condition with limited treatment options, mutations in the gene for the copper-zinc superoxide dismutase enzyme (SOD1) have been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, these mutations are associated mostly with familial ALS, which accounts for only about 5-10% of cases. So even when a predisposing genetic factor for a certain illness is identified, there may be other issues involved that cause the condition in people without the genetic susceptibility.

Switching gears from neurodegeneration to autoimmunity, the interplay between genetics and epigenetics is responsible for various autoimmune conditions. For example, people with celiac disease have increased risk for developing type 1 diabetes, and vice-versa. Both are linked to the “high-risk genotypes”  HLA-DQ8 and DQ2, but these conditions are likely not entirely genetic in origin. As one paper pointed out, the incidence of these conditions has been increasing for decades, and identical twins are not equally afflicted. If these genes have existed for millennia but incidence of these conditions is increasing, then as appears to be true for Alzheimer’s and ApoE4, by itself, the genes are not responsible for causing the condition. Rather, it’s the interaction of these genes with something in the modern environment (including the diet) that may be bridging the gap between susceptibility and actually triggering the illness.

From this perspective, gaining a deeper understanding of human genetics and susceptibility factors will be helpful, but we will also need to identify the factors that turn susceptibility into a condition. Knowing that certain genes are associated with increased risk for various disorders is helpful only if we know what specific factors in the diet or environment should be either emphasized or avoided in order to minimize risk. For example, in the case of ApoE4, it seems that high-carbohydrate diets and diets deficient in omega-3 fats may have a detrimental effect on lipid processing, which may be associated with Alzheimer’s.

Mutations in the BRCA1 and BRCA2 genes are associated with significantly increased risk for breast cancer in both women and men. Type 2 diabetes and insulin resistance are associated with increased risk for breast cancer as well. According to a review looking at associations between breast cancer and diabetes among women with BRCA1 or BRCA2 mutations, after a breast cancer diagnosis, women with these mutations had double the risk for developing diabetes, particularly if they have a high body mass index (BMI). However, a limitation of this study is that levels of insulin and its metabolites were not measured, so it’s possible that these women had insulin resistance (a precursor to type 2 diabetes) for some time prior to their cancer diagnosis, and hyperinsulinemia—even in the absence of hyperglycemia—is suspected to contribute to development and progression of cancer. (As the study authors pointed out, it’s also possible that something about the cancer treatment itself may have triggered the diabetes.) Elevated blood sugar, however, is also linked to increased incidence of several different types of cancer, which may underlie the exploration of metformin as an adjuvant in cancer therapy, including breast cancer. There may be a rationale for women with increased genetic susceptibility to breast cancer to implement diet and lifestyle strategies that would help them maintain healthy blood glucose and insulin levels (this may be even more important with regard to reducing risk for cancer recurrence), although this is speculative at the current time. 

Discoveries in human genetics and the associations between genes and susceptibility to various diseases hold promise for reducing global disease burden. But much more research remains to be done to determine the diet, lifestyle, and environmental practices—if any—that may sever the links between susceptibility and actual development of disease.