10/19/2017. How Nutritional Genomics Affects You in Nutrition Research and Practice Joyanna Hansen, PhD, RD & Kristin Guertin, PhD, MPH
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1 Disclosures Joyanna Hansen How Affects You in Nutrition Research and Practice Joyanna Hansen, PhD, RD & Kristin Guertin, PhD, MPH Consultant Nutricia North America Research Support Academy of Nutrition & Dietetics Pediatric Nutrition Practice Group, National Institutes of Health Disclosures Kristin Guertin Research Support University of Virginia Contractor Millennium Health & Fitness Learning Outcomes Explain the novel concepts of nutritional genomics and single nucleotide polymorphisms. Elaborate examples of diet and gene relationships. Apply knowledge of nutritional genomics to nutrition research and nutrition assessments. Evidence for Identifying Nutrient Needs at a Population Level National surveys Epidemiologic studies Lab-based studies National Health and Nutrition Examination Survey (NHANES) Started in 1960s continuous survey since 1999 Examines a nationally representative sample (~5,000 individuals per year) Over-sample African Americans, Hispanics, and individuals aged >60 years 6 1
2 NHANES In-home interview queries: demographic socioeconomic health-related issues NHANES Mobile Examination Clinic (MEC) Examination measurements: Medical Dental Physiological measurements Laboratory tests Participants receive compensation and report of medical findings NHANES: Assessing Usual Diet 24- hour dietary recall data What We Eat in America Day 1 in-person Day 2 by telephone 3-10 days later Supplement use Diet behaviors E.g. dietary modifications due to health conditions Food Frequency information NHANES Applications Determine the prevalence of major diseases and risk factors for diseases Assess nutritional status & association with health promotion and disease prevention Basis for national standards for measurements of height, weight, blood pressure : Food Frequency Questionnaire But.. 10 People Have Different Nutrient Needs! What Influences Variations in Needs? (RDA) Age Sex Body size Physical activity level Genetics! Example: genetic variation in genes that metabolize vitamin D 11 Hollis and Wagner, 2006, CMAJ 12 2
3 What is? What is? Position of the Academy of Nutrition and Dietetics:, Position of the Academy of Nutrition and Dietetics:, Epigenome Chemical compounds that can tell the genome (DNA) what to do Can attach to DNA and turn genes on/off Controls production of proteins in cells Can change due to lifestyle and environmental exposures Examples: Methylation: chemical tags attached to DNA Histone modification What is? Position of the Academy of Nutrition and Dietetics:, Omics Transcriptomics Gene expression Proteomics All proteins in the body Constantly changing in response to environment Metabolomics All metabolites/biomarkers in the body Result of all molecular events and physiological processes in the body Multidisciplinary Omics Approaches Can Improve Scientific Knowledge Inter-individual variability in nutrient needs True associations between diet and disease outcomes Improve understanding of conflicting findings from prior observational and randomized trials Better definitions of exposure with molecular markers, versus self-report 3
4 What is? What is? Position of the Academy of Nutrition and Dietetics:, Position of the Academy of Nutrition and Dietetics:, The Promise of Personalized Nutrition Your genome (looking at 1 of 2 copies) 23 chromosomes Goal: predict nutrient requirements/responses via genetic testing + provide individualized nutrition advice ~3,000,000,000 base pairs ~20,000 protein-coding genes Human genomes are 99.9% similar to each other! 21 Image: National Library of Medicine 22 DNA Changes Exons & Introns SNP: Single Nucleotide Polymorphism A single DNA base-pair difference. Example: A > G Exon: protein-coding region of a gene Intron: non-protein coding region of a gene (regulatory region) Protein J Acad Nutr Diet. 2014;114:
5 Impact of DNA Changes Genome-Wide Association Studies (GWAS) Many traits and diseases result from a combination of multiple genetic changes & environmental risk factors DNA changes can have very different consequences: Silent (no observable change) Subtle (change in eye color) Serious clinical consequences ( 3 Tablespoons salt breast cancer risk) White sugar Olive oil 25 GWAS: large-scale comparisons of the frequency of genotypes at many SNPs between people with distinct traits (example: diabetes or not) GWAS of T2DM Frazer et al Nat Rev Gen. 26 Coffee & Myocardial Infarction (MI) Risk How does genotype influence response to dietary intake and health status/disease risk? Studies looking at the association between coffee & myocardial infarction (heart attack) inconclusive Coffee is a major source of caffeine 1,3,7-trimethyl-xanthine CYP1A2 metabolizes ~95% of ingested caffeine Significant variability in enzyme activity CYP1A2 A C substitution (SNP) at position 734 of CYP1A2 gene results in impaired caffeine metabolism = CYP1A2*1F allele
6 CYP1A2 Genotypes Genotype CYP1A2*1A/CYP1A2*1A CYP1A2*1A/CYP1A2*1F CYP1A2*1F/CYP1A2*1F Caffeine Metabolism rapid slow slow Case-control study; 2,014 MI cases & 2,014 controls High coffee intake ( 4 cups/day) associated with risk of MI only among individuals with the slow metabolizer CYP1A2 genotype Individuals with fast metabolizer genotype had no increase in MI risk Clinical application: CYP1A2 genotype associated with differences in caffeine metabolism & cardiovascular risk Mendelian Randomization Basic concepts: Individuals are randomized to genetic variants at birth Study exposure = presence/absence of a risk allele that influences risk factor of interest Study Design Large prospective cohort study (>45,000 individuals) 4 SNPs genotyped in CRP gene CRP levels measured Study Results CRP polymorphisms associated with markedly CRP levels but not with risk of heart disease Figure: UpToDate Increased CRP levels may simply be a marker of heart disease and not a causal risk factor What is? Dietary components can directly or indirectly / gene expression Dietary components can activate / inhibit proteins Position of the Academy of Nutrition and Dietetics:, 2014 DeBusk 2010; Weaver, Adv Nutr
7 Long-Chain Polyunsaturated Fatty Acids Structural components of cell membranes Precursors for bioactive lipids Gene regulators! N-3 PUFAs: Mechanism N-3 PUFAs alter gene expression via inhibition/activation of transcription factors Source: Linus Pauling Institute Deckelbaum et al Genetic Testing What are the benefits and limitations of elective genetic testing? Identity Paternity/maternity testing Forensic testing Ancestry testing Clinical/Health Clinical diagnostic testing Carrier testing Pharmacogenomic testing Elective testing 39 Key Questions: Genetic Testing Key Questions: Genetic Testing Analytical validity Is the test accurate? Clinical validity How strong is the evidence that a particular genetic variant is related to the presence, absence, or risk of a specific disease (or nutrient response)? Clinical utility How likely is it that a genetic test will improve health outcomes? 41 Source:
8 Elective Genetic Testing Resources* Genetic Testing Pros Cons - Satisfaction in knowing more about your genome - Understanding reproductive risks - Discovery of potentially actionable information about nutrition and/or health risks - Increased motivation to make diet and/or lifestyle changes (?) - Loss of privacy - Psychological/social stress - Limited access to genetic counseling - Disappointment in how little data is interpretable/actionable 23andMe Ancestry Pathway Nutrigenomix mydnahealth * Not a comprehensive list! Arivale Vitagene SNPedia SNP Encyclopedia Promethease analysis tool for raw genetic data
9 Applications to Clinical Practice Future Research Needs ASSESSMENT Current Dx Demographics Family Hx Dietary Intake Physical Activity Medications Genetics INTERVENTION General guidelines (limit saturated fat intake) Behavioral change guidelines Nutrition guidance (meal plans, cooking tips) Specific genotype guidance (<1 cup of coffee/day) Better understanding of genotype phenotype correlations Web-based catalogs of diet-related SNPs Web-based tools for personalized nutrition Studies looking at effect of genotype knowledge on health/wellness outcomes Practice Applications THANK YOU! Understand the pros/cons of nutrition-focused genetic testing Apply knowledge of nutritional genomics to nutrition research Answer client/patient questions about nutrigenetics 52 9
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