Tuesday, January 17, 2012

Delaying parenthood has serious medical risks for both men and women, study warns

Delaying parenthood has serious medical risks for both men and women, study warns

Jan 17, 2012 – 9:48 AM ET
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Babies born to fathers of “advanced paternal age” — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors
By Sharon Kirkey
Men, and not just women, need to be aware of the “reproductive consequences” of postponing parenthood, new national guidelines on the risks of delayed child-bearing warn.
Though women especially should recognize that their “fecundity and fertility” starts to decline precipitously after 32, a man’s semen quality and fertility also worsens with age, according to guidelines endorsed by the Society of Obstetricians and Gynaecologists of Canada.
In addition, babies born to fathers of “advanced paternal age” — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors.
The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.
If the trend holds, society can expect to spend more on intensive care, special care nurseries and community services for children born to older parents who may have developmental, hearing, speech or language problems, the authors say.
It could also affect the future growth of the country; women who postpone their first births tend to have fewer babies, if they become pregnant at all.
“Widespread pre-conception counselling and education are needed and must be implemented so that the 95 per cent of Canadians who anticipate parenting at some point can make informed decisions,” the authors write in this month’s issue of the Journal of Obstetrics and Gynaecology Canada.
But while the popular belief is that women are deferring motherhood for their careers, a related survey of more than 1,000 women in Calgary and Edmonton who gave birth to their first child between 2002 and 2003 found that the top three factors influencing timing of pregnancy — regardless of a woman’s age — are relationship security, feeling in control of their life and feeling prepared to be a mother.
Less than a third of women cited career goals, though women more than 35 were more likely than younger women to say they felt their biological clock was ticking.
“We were really surprised, because that was the colloquial dogma — ‘Oh, I need to get my career underway,’ ” said Suzanne Tough, a professor in pediatrics and community health sciences at the University of Calgary and a co-author of the study, as well as the guideline on delayed child-bearing.
“Once women hit 25 . . . it was really the relationship that was the key factor in influencing when they chose to become a parent.”
The concern is that women may not realize what they’re risking while they’re waiting.
For females, the biologically optimum period for having a baby is between 20 and 35. By age 32, a woman’s fecundity — the probability of getting pregnant in a menstrual cycle — starts an irreversible slide.

Postponing parenthood could have serious consequences, warns new study

consequences, warns new study







By Sharon Kirkey, Postmedia News January 17, 2012 10:13 AM
















The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.

Photograph by: Thinkstock, canada.com


Men, and not just women, need to be aware of the "reproductive consequences" of postponing parenthood, new national guidelines on the risks of delayed child-bearing warn.


Though women especially should recognize that their "fecundity and fertility" starts to decline precipitously after 32, a man's semen quality and fertility also worsens with age, according to guidelines endorsed by the Society of Obstetricians and Gynaecologists of Canada.


In addition, babies born to fathers of "advanced paternal age" — defined as 40 and older at the time of conception — are at increased risk of genetic disorders, as well as schizophrenia, autism and some forms of cancer, according to the authors.


The new guideline to doctors comes amid growing concerns about the number of women delaying childbearing. In Canada, 11 per cent of first births now occur in women aged 35 and older, up from five per cent in 1987.


Read more: http://www.canada.com/health/Postponing+parenthood+could+have+serious+consequences+warns+study/6007363/story.html#ixzz1jjqxZIxQ

Wednesday, January 11, 2012

James F. Crow, 1916-2012

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James F. Crow, 1916-2012
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Wed, 2012-01-04 23:23 -- John Hawks




I received today the sad news that my friend and colleague James F. Crow has died, at the age of 95. Jim was a legend in the field of population genetics, who remained active until his final year.



Jim was always extraordinarily gracious and generous with his time, and was kind to me throughout the ten years I have known him. At our last meeting, before I went to Siberia last summer, Jim told me the story of his meeting Dmitry Belyaev, early in the days of his famous fox experiment. I was eager to see the foxes and I conveyed Jim's greetings and reminiscences to the researchers in Novosibirisk. Again and again during the years, I found Jim to be a rich source of information about topics in population genetics. Even as my work brought me to consider fundamentals often outside the current mainstream, Jim invariably had encountered similar problems and given them deep thought long before I arrived on the scene.

During the last 25 years, Jim took on a role as unofficial historian for the field of genetics. He coedited the Perspectives feature in the journal Genetics, and for many of those years wrote the lion's share of them. He was proud to note that his birth coincided with the first issue of the journal (January,1916), but although he arrived on schedule, the first issue of the journal was mailed two months late! Reviewing the major figures in the history of genetics, Jim gave a narrative history of the science often from his own memories.

During the next few months, the journal Genetics will be running a series of perspectives in Jim's honor, reviewing aspects of his extraordinary career. I recommend the introduction to the series, printed in the December 2011 issue [1], and the first entry written by Daniel Hartl about Jim as a teacher and advisor [2]. From the editorial introduction by Michael Turelli and Charles Langley:


Jim Crow is a living link between our generations and the founders of population genetics. Jim was Sewall Wright's colleague at the University of Wisconsin, Madison, for decades (1955–1988); Jim initiated a friendship with Ronald Fisher over an impromptu champagne tête-à-tête in the 1940s; and he hosted J. B. S. Haldane for a memorable lecture visit to Madison in the early 1960s (after learning from the New York Times that North Carolina had just canceled a public lecture by this famous Communist). There are few population geneticists who do not owe Jim a significant intellectual debt; none are unaware of his mastery of our field and of human interactions. For many of us, Crow and Kimura (1970) was an inspiring and elegant introduction to the mathematical models that form the foundation of population genetics theory. Crow instantiates the ideal of a cherished era when manners and dress were a sign of gentility. And no one who meets Jim is surprised to learn that he is an accomplished violist.

And from Hartl's contribution:


Professor Crow ran his laboratory on the principles of bringing smart people together to pursue their passions and encouraging interaction, mutual respect and support, constructive criticism, and the free sharing of ideas and resources. There were no formal group meetings or reports, as there was so much daily interaction that group meetings would have been superfluous. He would advise, suggest, and encourage, but never direct or cajole. The standard of mutual respect was set by Professor Crow himself and extended not only to members of the lab but also to everyone in the field. I never heard him utter an unkind word about anyone. He also treated everyone in the lab as a colleague. One day he came to me and said, “Dan, there’s a matter on which I’d like your advice.” He must have seen how flattered I was at being asked because he quickly added, “That doesn’t mean I’ll take it. It only means I want to hear it.”

Hartl gives some of the flavor of Crow's laboratory in the 1960's, when he was already one of the most prominent geneticists in the world, and was a frequent host to the field's legends and advisor to some of the brightest students. I can only wish that someday I will be so lucky.

Several years ago, colleagues from several departments here at the University of Wisconsin-Madison succeeded in a long-time ambition of Jim's to found an Institute for the Study of Evolution. He had envisioned that the institute should be named for Sewall Wright, who had been important to Jim himself and forms a major part of the legacy of genetics and evolution. But the future institute's members insisted instead to name the new entity in honor of Jim. It is a fitting legacy for a great evolutionary geneticist.

--------------------------------------------------------------------------------

References

1.Turelli M, and Langley C. 2011. Honoring our colleague James F. Crow, an outstanding gentleman, citizen, and scientist. Genetics 189:1127.
2.Hartl DL. 2011. James F. Crow and the art of teaching and mentoring. Genetics 189:1129-33.


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Synopsis:


In memory of a friend and colleague, one of the most prominent figures in the history of genetics
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James F. Crow, Population Genetics Pioneer, Dies at 95

James F. Crow, Population Genetics Pioneer, Dies at 95

James Crow Dies

James Crow Dies

January 11, 2012





James Crow, who was a population geneticist at the University of Wisconsin-Madison, has died, reports The New York Times. He was 95. Crow studied mutational load, and was part of on a National Academy of Sciences committee that assessed mutational damage to the populations of Hiroshima and Nagasaki following the use of atomic bombs there. He also was on a committee that paved the way for using DNA forensics in court. The Times notes that when Crow began teaching in the 1940s and 1950s, the field of genetics underwent rapid changes. "When anxious students asked Dr. Crow what would be in the exams, he would tell them that the questions were the same every year but that the answers were different," the Times says.

Saturday, January 07, 2012

High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia.

Neuron. 2011 Dec 22;72(6):951-63.

High Frequencies of De Novo CNVs in Bipolar Disorder and Schizophrenia.

Malhotra D, McCarthy S, Michaelson JJ, Vacic V, Burdick KE, Yoon S, Cichon S, Corvin A, Gary S, Gershon ES, Gill M, Karayiorgou M, Kelsoe JR, Krastoshevsky O, Krause V, Leibenluft E, Levy DL, Makarov V, Bhandari A, Malhotra AK, McMahon FJ, Nöthen MM, Potash JB, Rietschel M, Schulze TG, Sebat J.


Source

Beyster Center for Genomics of Psychiatric Diseases, University of California, San Diego, La Jolla, CA 92093, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 12824, USA.


Abstract

While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

Copyright © 2011 Elsevier Inc. All rights reserved.


PMID: 22196331 [PubMed - in process]

Wednesday, January 04, 2012

The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years.




Encephale. 2011 Jun;37(3):199-206. Epub 2011 Apr 2.

[Influence of paternal age in schizophrenia].

[Article in French]

Hubert A, Szöke A, Leboyer M, Schürhoff F.


Source

Pôle de psychiatrie du CHU de Créteil, groupe hospitalier Henri-Mondor-Albert-Chenevier, AP-HP, 40, rue Mesly, 94000 Créteil, France.


Abstract

BACKGROUND:

Schizophrenia is an aetiologically heterogeneous syndrome, with a strong genetic component. Despite a reduced fertility in this disorder, its prevalence is maintained and could be explained by de novo genetic mutations. Advanced paternal age (APA) is a major source of new mutations in human beings and could thus be associated with an increased risk of developing schizophrenia in offspring. New mutations related to APA have been implicated as a cause of sporadic cases in several autosomal dominant diseases and also in neurodevelopmental diseases, autism, intellectual disabilities, and social functioning. The aim of the present study was to summarize the results of studies investigating the role of APA, and to discuss some interpretations.

METHODS:

All relevant studies were identified through the National Library of Medicine (PubMed(®) database). Keywords used for research were "age" and "schizophrenia" linked to "paternal or father". We have identified and analysed eight cohort studies, five case-control studies, two meta-analyses, and one review concerning different father's mutations potentially transmitted, two studies comparing paternal age at conception between sporadic versus familial cases of schizophrenia. All studies selected have been published between 2000 and 2009.

RESULTS:

After controlling for several confounding factors including maternal age, the relative risk of schizophrenia increased from 1.84 to 4.62 in offspring of fathers with an older age of fatherhood. Mother's age showed no significant effects after adjusting for paternal age. There was a significant association between paternal age and risk of developing schizophrenia, there was a weaker association with psychosis.

DISCUSSION:

The results of these different studies are confirmed by two recent meta-analyses which found an increased risk of schizophrenia in offspring of fathers older than 35 years. Two main hypotheses could explain these results. The first one is based on the presence of new mutations in the spermatogonia, possibly because of accumulating replication errors in spermatogonial cell lines. This hypothesis is confirmed by Malaspina et al. (2002) [19], who found that patients without a family history of schizophrenia had significantly older fathers than probands with a positive family history of schizophrenia. However, this result has not been confirmed by other studies, and paternal age effect could be also explained by a mechanism called imprinting, which is a form of gene regulation. The second hypothesis is based on the fact that fathers with schizophrenia spectrum personality disorder, known to be genetically related to schizophrenia, could have an advanced age at conception. However, regarding this hypothesis, advanced maternal age at conception should be a risk factor for schizophrenia, and this is not the case. Thus, the first hypothesis seems more plausible than the second. APA has been identified as a risk factor for other psychiatric disorders such as autism, bipolar disorder, obsessive-compulsive disorder, and phobia, and thus seems to be a non-specific risk factor. Furthermore, its association with impaired neurocognitive outcomes during infancy and childhood in normal populations raises the question of the phenotype linked to APA.

CONCLUSION:

APA at conception appears to be a risk factor for schizophrenia. This risk factor probably interacts with genetic factors in a gene-environment interaction. To date, there is no validated cut-off at which the risk is significantly increased in offspring. In the future, studies could benefit from analyzing the phenotype related to APA.

Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.


PMID: 21703435 [PubMed - indexed for MEDLINE]


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