Empiric Risks

Note: The empiric risks presented in this document are representative of the research literature. You are encouraged to review the literature when considering risk for a client. In this chart we have listed disorders that occur more frequently in family members of individuals with the disorder in question. This does not necessarily mean that these disorders share a genetic etiology, or that they should be considered genetically similar for risk assessment purposes.

1. Anxiety Disorders
Lifetime prevalence for any anxiety disorder: 15-25%

Lifetime prevalence for panic disorder: 3.5%
Risk to first degree relatives: 8-31%
Early onset subtype is more familial
MZ concordance 22-73%, DZ 0-17%
Heritability estimated at about 40%
Possibly genetically related to agoraphobia
Lifetime prevalence for agoraphobia: 6.7%

Lifetime prevalence for generalized anxiety disorder: 5.1%
Limited family study data available
Risk to first-degree relatives ~20%

Lifetime prevalence for social phobia: 13.3%
Limited family study data available
Risk to first-degree relatives: 3-10 fold relative risk
May be genetically related to specific phobias
Commonly comorbid disorders
Unipolar Depression
Bipolar disorder, especially in those with panic disorder (this may be a distinct subtype of bipolar disorder)
Substance abuse
Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Unipolar depression (data indicate shared genetic etiology between unipolar depression and generalized anxiety disorder; panic disorder seems to have distinct genetic components)
Substance abuse

Note: In general, anxiety disorders tend to “breed true” in families, with the exception of panic disorder and phobic disorders; more common among females than among males; onset typically in mid-adolescence through young adulthood

 

Obsessive Compulsive Disorder
Lifetime prevalence of ~3%
1:1 M:F ratio
Onset generally in adolescence or early adulthood, but may begin in childhood. Modal onset for males between 6-15 years, for females 20-29 years.
Note: Onset is generally gradual, but may be acute in some instances; obsessions and compulsions might differ among family members

Early onset suggests higher genetic risk for family members; some studies suggest increased risk only in the case of early age at onset (generally defined as before 18 years)
Increased severity and chronicity appear to increase risk
Research has not ruled out a gene of major effect

Risk to 1st degree relatives:
Onset before age 18: range of ~10-35%
Onset after age 18: no increased risk to ~15%
MZ Twin concordance: 53-87%
DZ Twin concordance: 22-47%
Commonly comorbid disorders
Tourette syndrome (5-7% with OCD also have Tourette syndrome)
Chronic tics
Major depressive disorder

Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Major depressive disorder
Other anxiety disorders
Tourette syndrome
Obsessive-compulsive personality disorder
Chronic tics
ADHD

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2. Major Depressive/Unipolar Disorder
Community samples provide lifetime risk of 10-25% for women and 5-12% for men
(with higher end of range generally reflecting single depressive episodes as opposed to multiple episodes)
M:F sex ratio 1:2-3
Mean age at onset: 27-30 years
Significant risk for suicide: up to 15% with severe disorder
Significant chance to develop into Bipolar I Disorder (5-10% of those with single MDD; 10-15% of adolescents with recurrent MDD)

Age adjusted risk of MDD to first-degree relatives: 5-30%, relative risk 1.1-4.0

MZ Twin concordance for MDD: 40%
DZ Twin concordance for MDD: 11%

Heritability: Unclear (~20-80%); meta-analysis reports 31-42%

Note: Early onset and recurrent episodes likely increase risks to first-degree relatives. Recurrence risks for unipolar depression could be 50 percent or higher for probands with early onset and recurrent episodes. While the definition of “early onset” is not entirely clear, research suggests that family members of probands who had onset before age 25-30 years have the highest risk; relatives of probands with onset between ages 25-40 years have an intermediate risk; and relatives of probands with onset after age 40 years have a risk that is only slightly increased over the population risk.
Commonly comorbid disorders
Anxiety disorders
Alcoholism and substance abuse
Eating disorders
Borderline personality disorder
Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Anxiety disorder
Alcoholism (likely due to shared environmental rather than genetic factors)
Dysthymia
ADHD

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3. Bipolar disorder
Population prevalence: 0.8-1.6% (approximately 1%)
Median age at onset: 18-23 years; mean age at onset 25-33 years
Significant risk of suicide: 10-15%

Risk to first-degree relatives:
For bipolar disorder 5-20%, relative risk 7-10
For unipolar disorder 8-28%, relative risk 2-3
For any major affective disorder 20-30%

Risk to offspring with one parent affected with either bipolar, unipolar, or schizoaffective disorder is 27% (i.e., risk is 27% to have any of the three disorders)

Risk to offspring with both parents affected by bipolar disorder: 50-65% risk for bipolar; 50-75% risk for any affective disorder

Risk to second-degree relatives: 5%

Heritability: ~60%

Early age-at-onset might indicate increased risk to relatives; female relatives at highest risk for any affective disorder. During postpartum period, women at increased risk for developing subsequent episodes.

Commonly comorbid disorders
Alcohol and drug use
Anxiety disorders
Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Unipolar depression
Schizoaffective disorder
Cyclothymia
Alcohol and drug abuse
Eating disorders
ADHD
Anxiety disorders

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4. Schizophrenia
Population prevalence: 1%
Mean age at onset: early 20s for males, late 20s for females

Parent of individual with schizophrenia: 5-10% risk
Sibling of individual with schizophrenia: 8-14% risk
Offspring of individual with schizophrenia: 9-16% risk
Offspring of two parents with schizophrenia: 46% risk
Uncle or aunt of individual with schizophrenia: 2%
Nephew or niece of individual with schizophrenia: 1-4%
Grandchildren of individual with schizophrenia: 2-8%
Half-sibling of individual with schizophrenia: 4%
First cousin of individual with schizophrenia: 2-6%

MZ twin concordance: 40-60%
DZ twin concordance: 10-16%
Heritability: ~80%

Note: Early age at onset and more severe illness may indicate higher risk to relatives
Commonly comorbid disorders
Substance abuse
Anxiety disorders
Mood disorders
Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Schizoaffective disorder
Schizotypal personality disorder
Paranoid personality disorder
Schizoid personality disorder
Unipolar/major depression

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5. Schizoaffective Disorder (SA)
Mean age of onset: 27 years
Population prevalence is 1%, estimated at 0.5%.

Morbid risk for 1st degree relatives of individuals with schizoaffective disorder:
Note: There are limited data available. The risk ranges below all include the population prevalence. There is evidence that subtypes of SA increase risk for a different range of conditions.
Schizophrenia (chronic) 1 – 11%
SA (chronic) 1 – 4%
SA (non-chronic) 1 – 6%
Other psychosis 0.5-7.0%
BPI/BPII 1-12%
Unipolar 5-27%

Risk to offspring with one parent affected with bipolar, unipolar, or SA is 27% (ie, risk to have any of the three disorders is 27%)

While this is a fairly new field of research, data indicate that risk to first degree relatives for ANY psychiatric disorder is higher in SA disorder than any other psychiatric disorder. The extent of heritability is unclear, although likely in the range of schizophrenia.

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6. Attention Deficit Hyperactivity Disorder
Population prevalence: 5.0-10.0%
4M:1F sex ratio

Risk to first-degree relatives: 15-60%, 2-6 relative risk
Risk to second-degree relatives: 3-9%, 0.5-0.8 relative risk
Heritability: ~70-80%

Risks are higher for male relatives and lower for female. It is unclear if recurrence risks are higher when the proband is female. Continuation of illness into adulthood may indicate increased risk to relatives.
Commonly comorbid disorders
Conduct disorder
Mood disorders
Anxiety disorders
Substance abuse
Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Unipolar depression
Bipolar depression (note: comorbid ADHD + BP might be a distinct form of ADHD illness, related to childhood onset of BP)
Oppositional disorder
Conduct disorder
Learning disorders
Anxiety disorders

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7. Autism Spectrum Disorders
Prevalence of autistic disorder (autism): approx. 1/1000

Prevalence of autism spectrum disorders (including Asperger, autism, PDD/NOS): approx. 1/100

Male to female ratio of 4:1, ratio closer to 1:1 if only dysmorphic children with MR are considered, ratio of 7:1 if only non-dysmorphic children with average or above average IQ are considered.

Risk of autistic disorder in siblings of individuals with idiopathic autism: 6-8%

Risk of autism spectrum disorder in sibling of individual with idiopathic autism: not known, but presumably higher than 6-8%

Risk of autistic disorder in sibling of individual with Asperger or PDD/NOS: not known

Risk for broader phenotype traits (speech delay, difficulties with reading/spelling, social reticence/awkwardness, poor social language abilities, social phobia, restricted interests/OCD type traits, anxiety/mood disorders) in first degree relatives of autistic individuals: 30%
Risk of autistic disorder in a sibling of 2 autistic children: 25-30%

MZ Twin concordance: 36-60% (only autism), 82% (include broader phenotype)
DZ Twin concordance: 0-6% (only autism), 30% (include broader phenotype)

Heritability: >90%
Commonly comorbid disorders
Mood disorders
Anxiety disorders
Tourette syndrome or tics
Seizure disorders
Disorders that may occur more frequently in family members (note: this does not necessarily indicate shared genetic etiology)
Mood disorders
Anxiety disorders
Speech and language disorders

 

This list was updated in April 2004. We thank the National Society of Genetic Counselors (www.nsgc.org) for allowing us to include materials from the 2003 Short Course on Psychiatric Genetics.

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