Document Detail

Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings.
MedLine Citation:
PMID:  23147713     Owner:  NLM     Status:  MEDLINE    
CONTEXT: It is unknown how genetic variants conferring liability to psychiatric disorders survive in the population despite strong negative selection. However, this is key to understanding their etiology and designing studies to identify risk variants.
OBJECTIVES: To examine the reproductive fitness of patients with schizophrenia and other psychiatric disorders vs their unaffected siblings and to evaluate the level of selection on causal genetic variants.
DESIGN: We measured the fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse and their unaffected siblings compared with the general population.
SETTING: Population databases in Sweden, including the Multi-Generation Register and the Swedish Hospital Discharge Register.
PARTICIPANTS: In total, 2.3 million individuals among the 1950 to 1970 birth cohort in Sweden.
MAIN OUTCOME MEASURES: Fertility ratio (FR), reflecting the mean number of children compared with that of the general population, accounting for age, sex, family size, and affected status.
RESULTS: Except for women with depression, affected patients had significantly fewer children (FR range for those with psychiatric disorder, 0.23-0.93; P < 10-10). This reduction was consistently greater among men than women, suggesting that male fitness was particularly sensitive. Although sisters of patients with schizophrenia and bipolar disorder had increased fecundity (FR range, 1.02-1.03; P < .01), this was too small on its own to counterbalance the reduced fitness of affected patients. Brothers of patients with schizophrenia and autism showed reduced fecundity (FR range, 0.94-0.97; P < .001). Siblings of patients with depression and substance abuse had significantly increased fecundity (FR range, 1.01-1.05; P < 10-10). In the case of depression, this more than compensated for the lower fecundity of affected individuals.
CONCLUSIONS: Our results suggest that strong selection exists against schizophrenia, autism, and anorexia nervosa and that these variants may be maintained by new mutations or an as-yet unknown mechanism. Bipolar disorder did not seem to be under strong negative selection. Vulnerability to depression, and perhaps substance abuse, may be preserved by balancing selection, suggesting the involvement of common genetic variants in ways that depend on other genes and on environment.
Robert A Power; Simon Kyaga; Rudolf Uher; James H MacCabe; Niklas Långström; Mikael Landen; Peter McGuffin; Cathryn M Lewis; Paul Lichtenstein; Anna C Svensson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA psychiatry     Volume:  70     ISSN:  2168-6238     ISO Abbreviation:  JAMA Psychiatry     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-02-20     Completed Date:  2013-03-17     Revised Date:  2013-12-13    
Medline Journal Info:
Nlm Unique ID:  101589550     Medline TA:  JAMA Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  22-30     Citation Subset:  AIM; IM    
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MeSH Terms
Anorexia Nervosa / epidemiology,  genetics
Autistic Disorder / epidemiology,  genetics
Bipolar Disorder / epidemiology,  genetics
Depressive Disorder / epidemiology,  genetics
Fertility / genetics,  physiology
Mental Disorders / epidemiology*,  genetics
Middle Aged
Schizophrenia / epidemiology,  genetics
Selection, Genetic* / genetics,  physiology
Sex Factors
Substance-Related Disorders / epidemiology,  genetics
Grant Support
//Medical Research Council
Comment In:
JAMA Psychiatry. 2013 Oct;70(10):1115   [PMID:  24089036 ]
JAMA Psychiatry. 2013 Oct;70(10):1115   [PMID:  24089037 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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