Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Natriuretic peptide system gene variants are associated with ventricular dysfunction after coronary artery bypass grafting.

BACKGROUND: Ventricular dysfunction (VnD) after primary coronary artery bypass grafting is associated with increased hospital stay and mortality. Natriuretic peptides have compensatory vasodilatory, natriuretic, and paracrine influences on myocardial failure and ischemia. The authors hypothesized that natriuretic peptide system gene variants independently predict risk of VnD after primary coronary artery bypass grafting. METHODS: A total of 1,164 patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass at two institutions were prospectively enrolled. After prospectively defined exclusions, 697 patients of European descent (76 with VnD) were analyzed. VnD was defined as need for at least 2 new inotropes and/or new mechanical ventricular support after coronary artery bypass grafting. A total of 139 haplotype-tagging single nucleotide polymorphisms (SNPs) within 7 genes (NPPA, NPPB, NPPC, NPR1, NPR2, NPR3, CORIN) were genotyped. SNPs univariately associated with VnD were entered into logistic regression models adjusting for clinical covariates predictive of VnD. To control for multiple comparisons, permutation analyses were conducted for all SNP associations. RESULTS: After adjusting for clinical covariates and multiple comparisons within each gene, seven NPPA/NPPB SNPs (rs632793, rs6668352, rs549596, rs198388, rs198389, rs6676300, rs1009592) were associated with decreased risk of postoperative VnD (additive model; odds ratios 0.44-0.55; P = 0.010- 0.036) and four NPR3 SNPs (rs700923, rs16890196, rs765199, rs700926) were associated with increased risk of postoperative VnD (recessive model; odds ratios 3.89-4.28; P = 0.007-0.034). CONCLUSIONS: Genetic variation within the NPPA/NPPB and NPR3 genes is associated with risk of VnD after primary coronary artery bypass grafting. Knowledge of such genotypic predictors may result in better understanding of the molecular mechanisms underlying postoperative VnD

Titin truncating mutations: A rare cause of dilated cardiomyopathy in the young

10.1016/j.ppedcard.2016.01.003Progress in Pediatric Cardiology4041-45PPCA

A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy

10.1038/s41436-018-0036-2Genetics in Medicine1-1

Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery.

Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after coronary artery bypass graft surgery. METHODS AND RESULTS: Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (SNPs) encompassing the 4q25 locus. Three SNPs were then assessed in a separately collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF and multiple comparisons, rs2200733, rs13143308, and 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0x10(-4) to 3.4x10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. CONCLUSIONS: In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons

Idade materna como fator de risco: estudo com primigestas na faixa etária igual ou superior a 28 anos La edad materna como un factor de riesgo: estudio com primigestas en la facha etaria igual o superior a 28 años Maternal age as a risk factor: a study on first time pregnant women with age equal or higher than 28 years old

Trata-se de estudo transversal, cujo objetivo foi analisar a idade materna como fator de risco ou não, através da verificação de intercorrências na gestação, parto e puerpério de primigestas com idade igual ou superior a 28 anos e das condições de nascimento e alta de seus recém-nascidos, comparando-as com o grupo de primigestas na faixa etária de 20 a 27 anos. Foi realizado em Botucatu/S.P., no período de janeiro de 1990 a junho de 1995. A análise estatística, discutida ao nível de 5% de significância, foi realizada através da prova de Mann-Whitney, teste de Goodman e avaliação do risco relativo e risco relativo corrigido, através da técnica de Mantel-Haenszel. Concluiu-se que a idade materna igual ou superior a 28 anos não constituiu fator de risco gestacional, puerperal e intra-parto mas, por outro lado, foi fator de risco, mesmo após controlado o tipo de parto, para as seguintes intercorrências perinatais: taquipnéia transitória do recém-nascido, cianose generalizada ao nascer e infecção neonatal.<br>Es un estudio que tiene por objetivo analizar la edad materna como factor de riesgo o no, a través de la verificación de complicaciones en la gestación, parto y puerperio de primigestantes con edad igual o superior a 28 años, así como también las condiciones de nacimiento y alta de sus recien nacidos, haciendo una comparación con los grupos de primigestas en la facha etaria de 20 a 27 años. Se realizó en Botucatu/SP, del enero, 1990 al junio, 1995. El análisis de las estadísticas discutidas, tuvo un nivel significante de 5%, estas fueron realizadas a través de la prueba de Mann-Whitney y teste de Goodman. La evaluación del riesgo relativo y riesgo relativo corregido, fueron hechas a través de la técnica de Mantel-Haenszel. Se concluye que la edad maternal igual o superior a 28 años no constituye un factor de riesgo gestacional, puerperal e intra-parto, pero por outro lado, fue un factor de riesgo, mismo después de controlado el tipo de parto, para las siguientes complicaciones perinatales: taquipnea transitoria del recien nacido, cianosis generalizada ao nacer e infección neonatal.<br>This is a transverse-type designed study with the aim analise maternal age as a risk factor, and as not a risk factor, through the verification of incidents during pregnancy, birth and puerperium of first time pregnant women with age equal or higher than 28 years old; as well as birth conditions and discharge of their newborns, comparing them with a group of first time pregnant women from 20 to 27 years old. The study was carried out in Botucatu, São Paulo, from January, 1990 to June, 1995. The statistical analysis, discussed at the level of 5% of significance, was developed through Mann-Whitney test, Goodman test and the evaluation of relative risk and corrected relative risk through Mantel-Haenszel technique. We concluded that maternal age equal or higher than 28 years old, is not a pregnancy, puerperal and intrapartum risk factor, although, on the other hand, it was a risk factor even after controlled parturition for the following perinatal incidents: newborn tachypnea, generalized cyanosis at birth and neonatal infection