This article explains the rapid growth in genetic testing available directly to consumers (DTC), highlighting how recent discoveries of DNA variants linked to common diseases have enabled companies to offer personalized risk assessments. Researchers have identified over 1,100 genetic variants associated with diseases like heart disease and diabetes through genome-wide association studies (GWAS), allowing tests that can identify individuals with significantly elevated risks (e.g., 10% of people have 1.6× average heart attack risk). While health providers have been slow to adopt these tests, DTC companies now offer comprehensive genome scans that provide disease risk estimates, ancestry information, and trait analysis, though concerns about test validity and psychological impacts remain.

Understanding Direct-to-Consumer Genetic Tests: Past, Present and Future

Table of Contents

• Background: The Genetics Revolution
• How Your Genome Works and What Tests Can Reveal
• The Evolution of Genetic Testing
• Addressing Concerns About Consumer Genetic Tests
• What This Means for Your Health
• Understanding Test Limitations
• Recommendations for Patients
• Future of Genetic Testing
• Source Information

Background: The Genetics Revolution

Over the past 15+ years, scientists have made unprecedented discoveries about how DNA variations influence disease risk. Before 2006, researchers had identified only a handful of genetic variants linked to major diseases. By 2009, this exploded to 1,108 robustly verified associations across 132 diseases and medical conditions. This breakthrough came through genome-wide association studies (GWAS), which analyze hundreds of thousands of genetic markers simultaneously.

Four key developments enabled this progress:

• The Human Genome Project and HapMap Project that cataloged human genetic variation
• Advanced microarray technology allowing affordable testing of 500,000+ DNA variants at once
• Large collections of DNA samples from patients and healthy controls
• Strict scientific standards requiring replication of findings across studies

These discoveries provide crucial insights into diseases accounting for most modern health problems, including heart disease, diabetes, and cancer. While researchers continue hunting for more genetic links (including rare variants and gene interactions), we already have valuable data that could transform preventive healthcare.

How Your Genome Works and What Tests Can Reveal

Your genome contains 3 billion DNA letters that serve as instructions for building and maintaining your body. Genetic tests analyze variations in this code to predict:

• Disease risk: Your likelihood of developing specific illnesses
• Physical traits: Characteristics like eye color or baldness patterns
• Ancestry: Your genetic heritage and family connections

Some traits like phenylketonuria (a metabolic disorder) are controlled by a single gene. But most diseases involve dozens to hundreds of genetic variants plus environmental factors. For example:

• Heart attack risk involves at least 8 genetic variants plus lifestyle factors
• Each variant might only slightly increase risk (1.05-7× normal), but combined they create significant predictions

Ancestry testing examines how your DNA compares to global populations. While often considered "recreational," these tests indirectly assess disease risk too, since different populations have different genetic risk frequencies.

The Evolution of Genetic Testing

Genetic testing has evolved through three phases:

1. Traditional medical testing (through healthcare providers):
   • Focused on rare, high-risk mutations (e.g., BRCA genes increasing breast cancer risk 5×)
   • Required genetic counseling due to serious implications
   • Covered conditions like Huntington's disease or newborn screening
2. Specialized direct-to-consumer (DTC) tests:
   • Focused on single applications like ancestry or specific disease risks
   • Sold directly online without medical intermediaries
3. Comprehensive genome scans (current DTC standard):
   • Analyze 500,000 to 1 million DNA variants via microarray technology
   • Companies like deCODEme, 23andMe, and Navigenics offer these services
   • Provide ongoing updates as new discoveries emerge
   • Cover disease risks, traits, ancestry, and family connections

Despite over 1,000 verified disease associations, healthcare systems have been slow to adopt genetic risk screening for common diseases, creating an opportunity for DTC companies to fill this gap.

Addressing Concerns About Consumer Genetic Tests

Two main concerns arise regarding DTC genetic tests:

Concern 1: Test validity - Some argue that tests using common variants with small effects (odds ratios <2) have limited predictive power. However, combining multiple variants creates meaningful risk stratification. For example:

• deCODEme's heart attack test uses 8 variants to identify the 10% of Europeans with ≥1.4× higher risk
• These individuals have an average 1.6× risk elevation
• For men over 40 (42% average lifetime heart attack risk), this group has 67% risk

Concern 2: Psychological impact - Critics worry about anxiety from unexpected risk information. However, evidence suggests most users handle results appropriately. Companies provide educational resources to support understanding.

All major DTC companies use clinically validated variants from peer-reviewed studies and clearly explain risk as probabilities rather than diagnoses.

What This Means for Your Health

Genetic risk information empowers you to:

• Personalize prevention: Focus screening and lifestyle changes on your highest risks
• Detect diseases earlier: Increased monitoring for high-risk conditions
• Understand medication responses: Some tests predict drug metabolism

Combining genetic and conventional risk factors (age, weight, etc.) creates the most accurate predictions. For example:

• A man with high genetic heart attack risk (67% lifetime) could prioritize cholesterol management
• Early interventions may reduce complications by 40% in some conditions

This approach could significantly reduce healthcare costs by preventing late-stage disease treatment.

Understanding Test Limitations

Current genetic tests have important limitations:

• Incomplete risk coverage: Known variants explain only part of disease heritability (genetic contribution)
• Environmental factors: Lifestyle, diet, and toxins significantly influence risk
• Population specificity: Most data comes from European ancestry groups
• Functional understanding: We know variants are associated with disease, but not always how they cause it
• Rare variants: Current microarrays miss some important mutations

Tests provide probabilities, not certainties. A "high risk" result doesn't guarantee you'll develop a disease, while "average risk" doesn't make you immune.

Recommendations for Patients

1. Choose reputable companies: Select providers using clinically validated variants and clear scientific explanations
2. Review updates regularly: New discoveries may change your risk assessments
3. Combine with conventional screening: Genetic tests complement (don't replace) blood tests, imaging, and exams
4. Discuss with healthcare providers: Share results to inform prevention strategies
5. Consider counseling: Seek genetic counseling for concerning results (e.g., high cancer risk)
6. Focus on modifiable risks: Prioritize lifestyle changes for conditions you can influence

Future of Genetic Testing

Genetic testing will evolve through:

• Whole-genome sequencing: Replacing microarrays for comprehensive analysis
• Improved risk models: Integrating genetics, environment, and lifestyle factors
• New variant discovery: Investigating rare mutations and gene interactions
• Health system integration: Eventually becoming routine in preventive care
• Therapeutic development: New drugs targeting specific genetic subtypes

As costs decrease (full genome sequencing was ~$350,000 in 2010, now under $1,000), comprehensive testing will become increasingly accessible.

Source Information

Original Title: The past, present, and future of direct-to-consumer genetic tests
Authors: Agnar Helgason, DPhil; Kári Stefánsson, MD
Journal: Dialogues in Clinical Neuroscience
Publication Date: 2010
Volume and Issue: Vol 12, No. 1, pp 61-68
DOI: 10.31887/DCNS.2010.12.1/ahelgason

This patient-friendly article is based on peer-reviewed research from deCODE Genetics and academic collaborators. The authors are genetics researchers who contributed to both disease discovery and commercial test development.