Tuesday, October 25, 2011

Parental age as a risk factor for non-syndromic oral clefts: A meta-analysis.

J Dent. 2011 Oct 13. [Epub ahead of print]
Parental age as a risk factor for non-syndromic oral clefts: A meta-analysis.
Herkrath AP, Herkrath F, Rebelo MA, Vettore MV.
SourceInstituto Leônidas e Maria Deane, Fundação Oswaldo Cruz, Rua Terezina, 476 - Adrianópolis, Manaus, AM, CEP: 69.057-070, Brazil.

OBJECTIVES: A meta-analysis was conducted to assess the relationship between parental age and the occurrence of non-syndromic oral clefts. The questions addressed if younger or older mothers and fathers have an increased risk of having a child with non-syndromic oral clefts.

DATA: Data from cohort studies, case-control, cross-sectional and prevalence studies in which the association between parental age and oral clefts was investigated were analysed. Only studies on oral clefts not associated with syndromes or other anomalies were considered.

SOURCES: An electronic literature search were conducted in Medline, Embase, LILACS, SciELO, SCOPUS and the Cochrane library databases to identify original research published until November 2010. References of the selected articles were also searched.

STUDY SELECTION: The initial database search identified 4623 citations and according to eligibility criteria 80 articles were submitted to quality assessment. In 13 studies measures of association could be extracted for meta-analysis.

CONCLUSION: Our findings suggest that fathers forty years of age or older had a 58% higher probability of having a child with cleft palate compared to those aged between 20 and 39 years. The probability of mothers aged between 35 and 39 years having a child with cleft palate was 20% higher in comparison with those between 20 and 29 years-old, whilst for those aged 40 years or more this probability was 28% higher compared to those aged between 20 and 29 years. Mothers aged 40 years or over were 1.56 times more likely to have a newborn with cleft lip with or without palate compared to those aged between 20 and 29 years. No evidence of association between early maternal and paternal age with occurrence of oral clefts was observed.

Copyright © 2011. Published by Elsevier Ltd.

PMID:22019990[PubMed - as supplied by publisher]

Tuesday, October 18, 2011

Advanced paternal and grandpaternal age and schizophrenia

Schizophr Res. 2011 Oct 13. [Epub ahead of print]
Advanced paternal and grandpaternal age and schizophrenia: A three-generation perspective.
Frans EM, McGrath JJ, Sandin S, Lichtenstein P, Reichenberg A, Långström N, Hultman CM.
SourceDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

BACKGROUND: Advanced paternal age has been linked with an increased risk of schizophrenia in the offspring. If age-related de novo mutations in the male germ line underlie this association, grandpaternal and paternal age would both be expected to influence the risk of schizophrenia. The aim of the current study was to explore the links between both paternal and grandpaternal age with respect to the risk of schizophrenia in a large, national register-based cohort.

METHOD: We linked the Swedish Multi-Generation and Hospital Discharge Registers and compared parents' ages at offspring birth for 20,582 schizophrenia-affected and 100,176 non-affected individuals. Grandparents' ages at the birth of the parent were compared between 2511 affected and 15,619 non-affected individuals. The risk of schizophrenia was examined with logistic regression when the predictor variable (parent or grandparent age) varied across age strata.

RESULTS: After adjusting for maternal age, birth year and proband sex, we confirmed that offspring of older fathers had an increased risk of schizophrenia. Compared to those with paternal age 20-24years, those with fathers >55years had a two-fold increased risk of schizophrenia. With respect to grandparent age, older maternal (but not paternal) grandfather age was associated with an increased risk of schizophrenia. Compared to maternal grandfather age 20-24years, those with maternal grandfathers >55years had a significantly increased risk of schizophrenia (adjusted odds ratio and 95% confidence intervals; 2.79, 1.71-4.56). The pattern of results was essentially unchanged when we examined male and female probands separately.

CONCLUSION: This is the first study to report an association between grandpaternal age and risk of schizophrenia. The selective effect of advanced maternal grandfather age suggests that the biological mechanisms involving the X-chromosome may differentially contribute to the association between paternal age and offspring risk of schizophrenia.

Copyright © 2011. Published by Elsevier B.V.

Wednesday, October 05, 2011

Probable association between preeclampsia/eclampsia and paternal age: a pilot study

Ginecol Obstet Mex. 2011 Apr;79(4):190-5.
[Probable association between preeclampsia/eclampsia and paternal age: a pilot study].
[Article in Spanish]
García-Ortiz L, Gutiérrez-Salinas J, Galaviz-Hernández C, Chima-Galán Mdel C, Hilton-Cáceres JM, Escobedo-Aguirre F, de la Peña-Gutiérrez M, Iniesta-Mejía A, Miranda-Murillo J.
SourceLaboratorio de Medicina Genómica, Centro Médico Nacional 20 de Noviembre, ISSSTE, México. garortiz@yahoo.com

BACKGROUND: The preeclampsia is a multisystemic syndrome that occupied the first cause of maternal and fetal mortality around the world. Epidemiologic studies shown both mother and father contribute at the same risk for preeclampsia.

OBJECTIVE: To determinate if there is an association between preeclampsia and paternal age.

MATERIAL AND METHOD: Preeclampsia-eclampsia patients and couples were analyzed in agree to "National High Blood Pressure Education Program Working Group" classification, and a control group constituted by normal pregnant women and couples was included.

RESULTS: There were 27 cases with mild preeclampsia and her couples, 13 cases with severe preeclampsia and her couples and 40 controls conformed by normal pregnant women and her couples. The statistical analysis of variance of the ages shown that men from preeclamptic group had a greater variance in contrast with man of control group (p < 0.001; valor of F = 5.084).

CONCLUSIONS: Although is not clear how paternal age interview in preeclampsia risk, the interaction between paternal-maternal imprinting and spermatic senescence, followed by shortened telomeres of chromosome, could be produce the inactivity of a whole network of signals implicated in disease aetiology.

De novo copy number variants associated with intellectual disability have a paternal origin and age bias.

J Med Genet. 2011 Oct 3. [Epub ahead of print]
De novo copy number variants associated with intellectual disability have a paternal origin and age bias.
Hehir-Kwa JY, Rodríguez-Santiago B, Vissers LE, de Leeuw N, Pfundt R, Buitelaar JK, Pérez-Jurado LA, Veltman JA.
Source1Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences and Institute for Genetic and Metabolic Disorders, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

BackgroundDe novo mutations and structural rearrangements are a common cause of intellectual disability (ID) and other disorders with reduced or null reproductive fitness. Insight into the genomic and environmental factors predisposing to the generation of these de novo events is therefore of significant clinical importance.MethodsThis study used information from single nucleotide polymorphism microarrays to determine the parent-of-origin of 118 rare de novo copy number variations (CNVs) detected in a cohort of 3443 patients with ID.ResultsThe large majority of these CNVs (76%, p=1.14×10(-8)) originated on the paternal allele. This paternal bias was independent of CNV length and CNV type. Interestingly, the paternal bias was less pronounced for CNVs flanked by segmental duplications (64%), suggesting that molecular mechanisms involved in the formation of rare de novo CNVs may be dependent on the parent-of-origin. In addition, a significantly increased paternal age was only observed for those CNVs which were not flanked by segmental duplications (p=0.02).ConclusionThis indicates that rare de novo CNVs are increasingly being generated with advanced paternal age by replication based mechanisms during spermatogenesis.

PMID:21969336[PubMed - as supplied by publisher]