32 PD Genetic Testing and Disability Insurance
Moderator:
Margaret Donavan, FSA, MAAA
Presenter:
Bruce Margolis
Genetic Testing and Disability Insurance
A Medical Director’s Perspective
June 23, 2014
Company Confidential
©2012 Genworth Financial, Inc. All rights reserved.
©2014
Agenda
Genetics 101
– Basic genetic concepts
– Types of inheritance
– Current technology/cost
What is a genetic test/genetic information?
Current uses of genetic testing
Direct to consumer (DTC) genetic testing
Genetic testing and anti-selection
Genetics and disability insurance underwriting
Ethical considerations – NIH Working Group on Genetic Testing and
Disability Insurance
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Genetics 101
– DNA (deoxyribonucleic acid) strands are “blueprint”
– Deoxynucleoside pairs make up DNA strand or chain
• adenine (A) always pairs with thymine (T)
• cytosine (C) always pairs with guanine (G)
– Double helix made of paired strands of DNA
– Chromosome is one long segment of DNA:
• Total of 46: as 23 pairs, one from each parent
• 22 numbered: one to twenty-two
• One sex chromosome pair: XX female, XY male
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Genetics 101
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Genetics 101
Explosion of genetic science knowledge and technology
– Human Genome Project began 1990; completed 2003; cost $300M
– 3.1 billion base pairs
– 25,000 genes identified
– 99.9% identical across different people
– Less than 1% variation between people
• Variations known as polymorphisms
• A variation seen <1% is known as a “mutation”
www.genome.gov
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Genetics 101
Definitions
– Genome – the entire sequence of base pairs of inherited DNA
– Gene – a segment of DNA that typically codes for one protein
– Genotype – an individual’s total DNA sequence or single gene sequence
– Allele – one of several variants of a gene, usually referring to one location
– Large scale mutations
• Chromosomal disorders – Trisomy 21 (Down’s syndrome)
– Small scale mutations
• Insertion – addition of base pairs
• Deletion – removal of base pairs
• Repeating pattern or fragment
• Single nucleotide polymorphisms (SNP)
– Millions have been catalogued
– ~2-3 million per genome
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Genetics 101
Types of Inheritance
– Single Gene Disorders
• Autosomal dominant (inherited from one parent)
• Autosomal recessive (requires inheritance from both parents)
– Chromosomal Disorders
• Additional chromosome (e.g. Down’s syndrome)
• Loss of a chromosome (e.g. Turner’s syndrome – single X sex gene)
• Altered chromosome (e.g. Fragile X)
– Multi-factorial
• Polymorphism
• Multiple gene interaction
– Post-inheritance
• Epigenetics
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Genetics 101
Autosomal Dominant
– Familial hypercholesterolemia
– Polycystic kidney disease
– Neurofibromatosis type 1
– Hereditary spherocytosis
– Marfan syndrome
– Huntington’s disease
Autosomal Recessive
– Sickle cell anemia
– Cystic fibrosis
– Tay-Sachs disease
– Phenylketonuria
– Glycogen storage diseases
X-linked
– Duchenne muscular dystrophy
– Hemophilia
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Genetics 101
COST IS NOW $1000!
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Genetics 101
Genome-Wide Association Studies (GWAS)
– Rapid scanning of genetic markers across genome of groups with and without a
disorder or attribute
– Scanning looks for single nucleotide polymorphisms (SNPs)
– May scan entire genome of targeted area
– Useful for complex disorders such as asthma, cancer, diabetes, heart disease,
Parkinson’s, Crohn’s, mental illness
– Information may be helpful in detecting, treating or preventing a particular
disorder
– Identify relative risks
– Associations may not be causative
– Varying predictive power
– NIH maintains list of GWAS studies ( www.genome.gov/gwastudies )
www.genome.gov
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Genetics 101
Published GWA Reports, 2005 – 6/2012
1350
Total Number of Publications
1400
1200
1000
800
600
400
200
0
2005
2006
2007
2008
2009
Calendar Quarter
http://www.genome.gov/page.cfm?pageid=26525384&clearquery=1#result_table
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2010
2011
2012
Genetic Test/Genetic Information Defined
Genetic Test
– “The analysis of human DNA, RNA, chromosomes, proteins, and certain
metabolites in order to detect heritable disease-related genotypes,
mutations, phenotypes or karyotypes for clinical purposes.” (Task Force
on Genetic Testing – NIH/Department of Energy)
Genetic Information
–“Genetic information includes information about an individual’s
genetic tests and the genetic tests of an individual’s family
members, was well as information about the manifestation of a
disease or disorder in an individual’s family members (i.e., family
medical history…….Genetic information also includes an
individual’s request for, or receipt of, genetic services by the
individual or a family member of the individual…..” [Title II of the
Genetic Information Nondiscrimination Act of 2008 (GINA)]
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Current Uses of Genetic Testing
Carrier testing for family planning (Tay-Sachs, Cystic Fibrosis)
Prenatal diagnosis (Down’s syndrome)
Neonatal screening (Phenylketonuria)
Confirmation of a suspected disease (Huntington’s, Muscular
Dystrophy, Polycystic Kidney Disease, Hemochromatosis)
Identification of risk for disease (BRCA, APOE)
Screening for potential response to treatment (Warfarin, Clopidogrel)
Paternity testing
Crime investigation
Personal curiosity
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Direct to Consumer Genetic Testing
Market directly to consumers online
Simple saliva collection
Provide information on health risks (using SNP analysis), medication
sensitivities, inherited conditions and traits
Multiple providers
– 23andMe
– deCODEme
– GenePlanet
– ancestry.com
Test results of questionable accuracy, utility or value
Not FDA regulated
November 2013 – FDA notified 23andMe to stop marketing their
personal genome service
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Direct to Consumer Genetic Testing
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Direct to Consumer Genetic Testing
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Direct to Consumer Genetic Testing
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Direct to Consumer Genetic Testing
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Direct to Consumer Genetic Testing
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Evidence of Anti-Selection
Risk Evaluation and Education for Alzheimer’s Disease (REVEAL)
Study
– Randomized study evaluating the impact of a genetic education and counseling
program for adult children of Alzheimer’s disease (AD) patients
– 162 participants (August 2000 – October 2003); 148 analyzed
– Control arm (N=46) – participants informed of their risk of developing AD based
on gender and family history alone
– Intervention group (N=102) – 54 participants learned they were ϵ4 negative and
48 learned they were ϵ4 positive (one or two alleles)
– Primary outcome measures for REVEAL focused on social and psychological
impact of knowing one’s genotype
– Secondary outcome measures focused on insurance purchasing habits
Zick, et al. Health Affairs. 2005;24:483
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Evidence of Anti-Selection
Fraction of Participants Who Thought about Changing Insurance Coverage or Actually Changed
Insurance Coverage Over a One Year Period
Percentage Reporting an Actual Change
Percentage Reporting Thinking About
Making a Change
No APOE
Disclosure
ϵ4
Negative
ϵ4
Positive
No APOE
Disclosure
ϵ4
Negative
ϵ4
Positive
Health
Insurance
6.51
5.56
12.5
23.9
13.0
25.0
Life
Insurance
6.52
7.41
2.08
4.35
5.56
16.67
Disability
Insurance
4.35
3.70
4.17
8.7
7.41
18.8
Long-Term
Care
Insurance
4.35
1.85
16.7
32.6
22.2
45.8
Zick, et al. Health Affairs. 2005;24:483
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Genetics and Disability Insurance
Identification of those potentially at increased risk for disabling
conditions
– Mental/Nervous disorders
• bipolar disorder
• schizophrenia
– Progressive neurologic disorders
• multiple sclerosis
• Parkinson’s
• Alzheimer’s
• tremor
– Alcohol and drug dependency
– Vision impairment
• macular degeneration
– Cardiovascular disease
• stroke
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Genetic Information and DI Underwriting
Is Genetic Information Different than Other Health Information
for Underwriting Purposes?
NIH Working Group on Genetic Testing and DI - Recommendations
– Legislators should restrict the access and use of genetic information to DI insurers similar
to health insurers
– Legislators should insist that DI insurers treat genetic risk as they would actuarially treat
similar non-genetic risks
– Legislators should decide that DI insurers may not rate or reject an applicant on the basis
of genetic information in the absence of the manifestation and diagnosis of a predicted
condition
– Legislators should disallow exclusions based on genetic information
– Other recommendations relating to informed consent, confidentiality, notification of reasons
for adverse decisions and the formation of an advisory board on genetic testing
Wolf SM, Kahn JP. J Law, Med & Ethics. 2007;35:6
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Genetic Information and DI Underwriting
Is Genetic Information Different than Other Health Information
for Underwriting Purposes?
NIH Working Group on Genetic Testing and DI – Industry Alternative Opinion
– Disagreed with Wolf & Kahn definition of a genetic test as it could include commonly
ordered clinical tests
– Disagreed that genetic information is different than other health information (“genetic
exceptionalism”)
– Noted that not allowing an insurer to use a genetic marker without disease manifestation
will result in anti-selection, an insurer’s inability to adequately risk assess an applicant and
potentially negatively impact a product’s performance
– Successful underwriting requires a level playing field between the applicant and the insurer
Dodge JH, Christianson DJ. J Law, Med & Ethics. 2007;35:33
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Summary
The number of genetic markers/tests is increasing logarithmically
The cost of genetic sequencing has dropped to a fraction of a
penny/base pair
Most common diseases are not single gene disorders
Genome-wide association studies seek to identify single nucleotide
differences amongst populations
The clinical uses of genetic testing continues to increase, but
currently relate primarily to the identification of single gene disorders,
tumor markers, medication response with rare use of susceptibility
genes
The use of genetic information in insurance underwriting remains a
controversial issue
There needs to be a level playing field of information between an
applicant and an insurer to allow an adequate risk assessment and
avoid anti-selection
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