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4. Nonverbale Kommunikation in der Fernsehwerbung von Fazer und Milka

Author

Hämäläinen, E. (Ella)

Subjects
Saksan kieli ja kulttuuri
Abstract

Nonverbale Kommunikation ist eine viel ältere Form der Kommunikation als verbale Kommunikation, welche schon lange bevor der Mensch zu sprechen lernte verwendet wurde. Seit Tausenden von Jahren verwendet die Menschheit wortlose Botschaften, um Gedanken, Ideen und Emotionen durch Gesten, Körperhaltung und Geräusche zu kommunizieren. Die nonverbale Kommunikation wird seit den 1960er Jahren relativ intensiv erforscht. Im 21. Jahrhundert konzentriert sich die Forschung auf die nonverbale Kommunikation als Teil des Interaktionsprozesses und weniger auf einzelne nonverbale Botschaften. Obwohl die nonverbale Kommunikation in der Fernsehwerbung eine sehr wichtige Rolle spielt, ist sie in der Fernsehwerbung bisher kaum untersucht worden und wurde daher als Thema dieser Forschung gewählt. Diese Pro-Gradu-Arbeit beschäftigt sich mit der nonverbalen Kommunikation in der Fernsehwerbung von Milka und Fazer. Das Ziel dieser Arbeit ist herauszufinden, welche Formen der nonverbalen Kommunikation in den Fernsehwerbungen von Milka und Fazer vorkommen und welche von diesen Formen im unmittelbaren Umfeld des Produkts dargestellt werden. Finnland und Deutschland sind im kulturellen Kontext sehr ähnlich zueinander und deswegen wird auch untersucht, ob es Unterschiede in der nonverbalen Kommunikation wegen der Kultur beim vorliegenden Korpus gibt. Es wird auch betrachtet, welche Rolle die nonverbale Kommunikation beim Konsum des Produkts spielt. Ein anderes Ziel der Forschung ist herauszufinden, wie sowohl die nonverbalen als auch die verbalen Elemente als Argumentation benutzt werden. Der theoretische Teil der Arbeit befasst sich mit den für die Arbeit wichtigsten Themen: nonverbale Kommunikation, ihre Bereiche und kulturellen Besonderheiten sowie Werbung. Das Untersuchungsmaterial besteht aus vier Fernsehwerbungen, zwei von Milka und zwei von Fazer. Das Material und die Methodik werden nach dem theoretischen Teil vorgestellt. Die Analyse der Untersuchung ist in drei Teile eingeteilt und stützt sich auf die im theoretischen Teil behandelten Themen. Um die Daten so genau wie möglich zu analysieren, werden die Werbevideos zunächst auf einer pragmatischen-analytischen Ebene untersucht. Anschließend werden alle Elemente der nonverbalen Kommunikation, die in der Fernsehwerbung vorkommen, sowie die Rolle dieser Elemente beim Konsum des Produkts und die Verwendung sowohl nonverbaler als auch verbaler Elemente als Argumentationsmittel untersucht. Die Studie soll dazu beitragen, den Einsatz der nonverbalen Kommunikation in der Fernsehwerbung besser zu verstehen. Die Analyse zeigt, dass die nonverbale Kommunikation offensichtlich viele Möglichkeiten bietet, dem Empfänger Informationen zu vermitteln, insbesondere in Form von Emotionen, und daher ein wichtiger Faktor im Verbraucherverhalten ist.Tiivistelmä. Nonverbaalinen viestintä on paljon vanhempi viestinnän muoto kuin verbaalinen viestintä — sitä käytettiin jo kauan ennen kuin ihmiset oppivat puhumaan. Tuhansien vuosien ajan ihmiskunta on käyttänyt eleitä, asentoja ja ääniä välittääkseen ajatuksia, ideoita ja tunteita. Nonverbaalista viestintää onkin tutkittu suhteellisen ahkerasti 1960-luvulta lähtien. 2000-luvulla tutkimus on keskittynyt yksittäisten nonverbaalisten viestien tarkastelemisen sijaan nonverbaaliseen viestintään osana vuorovaikutusprosessia. Vaikka nonverbaalisella viestinnällä on erittäin tärkeä rooli televisiomainoksissa, ei sitä ole kuitenkaan juuri tutkittu televisiomainoksissa, ja siksi se valikoitui tämän tutkimuksen aiheeksi. Tämä pro gradu -tutkielma käsittelee nonverbaalista viestintää Milkan ja Fazerin televisiomainoksissa. Tutkielman tavoitteena on selvittää, mitä kaikkia nonverbaalisen viestinnän osa-alueita Milkan ja Fazerin televisiomainoksissa esiintyy ja ilmeneekö näissä kulttuurisia eroja. Nonverbaalisen viestinnän merkitystä tarkastellaan myös tuotteen kulutuksen yhteydessä. Tutkielman tavoitteena on myös selvittää, miten sekä nonverbaalisia että verbaalisia elementtejä käytetään argumentaatiokeinoina. Tutkielman teoriaosassa käsitellään tutkielman kannalta keskeisimpiä aiheita: nonverbaalista viestintää, sen osa-alueita ja kulttuurisidonnaisuutta sekä mainoksia ja mainontaa yleisesti. Tutkimusmateriaali koostuu neljästä televisiomainoksesta, joista kaksi on Milkan ja kaksi Fazerin. Materiaali ja metodiikka esitellään teoriaosan jälkeen. Tutkielman analyysi on jaettu kolmeen osaan ja se pohjautuu teoriaosassa käsiteltyihin aiheisiin. Tietojen mahdollisimman tarkan analysoinnin kannalta mainoksia tarkastellaan ensin pragmaattisanalyyttisellä tasolla. Tämän jälkeen tutkitaan mitä kaikkia nonverbaalisen viestinnän osa-alueita televisiomainoksissa ilmenee, minkälainen rooli kyseisillä osa-alueilla on tuotteen kulutuksen yhteydessä sekä selvitetään, miten sekä nonverbaalisia että verbaalisia elementtejä käytetään argumentaatiokeinoina. Tutkimus auttaa ymmärtämään paremmin nonverbaalisen viestinnän käyttötarkoitusta televisiomainoksissa. Analyysin perusteella voidaan todeta, että nonverbaalinen viestintä tarjoaa selvästi monia mahdollisuuksia välittää tietoa vastaanottajalle erityisesti tunteiden muodossa, ja on siten tärkeä tekijä kuluttajakäyttäytymisen kannalta.

Published
2022

5. Maternal early-pregnancy body mass index-associated metabolomic component and mental and behavioral disorders in children

Author

Girchenko, P. (Polina), Lahti-Pulkkinen, M. (Marius), Lipsanen, J. (Jari), Heinonen, K. (Kati), Lahti, J. (Jari), Rantalainen, V. (Ville), Hämäläinen, E. (Esa), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Kajantie, E. (Eero), Räikkönen, K. (Katri), Girchenko, P. (Polina), Lahti-Pulkkinen, M. (Marius), Lipsanen, J. (Jari), Heinonen, K. (Kati), Lahti, J. (Jari), Rantalainen, V. (Ville), Hämäläinen, E. (Esa), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Kajantie, E. (Eero), and Räikkönen, K. (Katri)

Abstract

Maternal pre-pregnancy obesity and/or higher body mass index (BMI) have been associated with neurodevelopmental and mental health adversities in children. While maternal metabolomic perturbations during pregnancy may underpin these associations, the existing evidence is limited to studying individual metabolites, not capturing metabolic variation specific to maternal BMI, and not accounting for the correlated nature of the metabolomic measures. By using multivariate supervised analytical methods, we first identified maternal early-pregnancy BMI-associated metabolomic component during pregnancy. We then examined whether this component was associated with mental and behavioral disorders in children, improved the prediction of the child outcomes over maternal BMI, and what proportion of the effect of maternal BMI on the child outcomes this component mediated. Early-pregnancy BMI of 425 mothers participating in the PREDO study was extracted from the national Medical Birth Register. During pregnancy, mothers donated up to three blood samples, from which a targeted panel of 68 metabolites were measured. Mental and behavioral disorders in children followed-up from birth until 8.4–12.8 years came from the Care Register for Health Care. Of the 68 metabolites averaged across the three sampling points, 43 associated significantly with maternal early-pregnancy BMI yielding a maternal early-pregnancy BMI-associated metabolomic component (total variance explained, 55.4%; predictive ability, 52.0%). This metabolomic component was significantly associated with higher hazard of any mental and behavioral disorder [HR 1.45, 95%CI(1.15, 1.84)] and relative risk of having a higher number of co-morbid disorders [RR 1.43, 95%CI(1.12, 1.69)] in children. It improved the goodness-of-model-fit over maternal BMI by 37.7–65.6%, and hence the predictive significance of the model, and mediated 60.8–75.8% of the effect of maternal BMI on the child outcomes. Maternal BMI-related metabolom

Published
2022

6. A novel variant in SMG9 causes intellectual disability, confirming a role for nonsense-mediated decay components in neurocognitive development

Author

Rahikkala, E. (Elisa), Urpa, L. (Lea), Ghimire, B. (Bishwa), Topa, H. (Hande), Kurki, M. I. (Mitja I.), Koskela, M. (Maryna), Airavaara, M. (Mikko), Hämäläinen, E. (Eija), Pylkäs, K. (Katri), Körkkö, J. (Jarmo), Savolainen, H. (Helena), Suoranta, A. (Anu), Bertoli-Avella, A. (Aida), Rolfs, A. (Arndt), Mattila, P. (Pirkko), Daly, M. (Mark), Palotie, A. (Aarno), Pietiläinen, O. (Olli), Moilanen, J. (Jukka), Kuismin, O. (Outi), Rahikkala, E. (Elisa), Urpa, L. (Lea), Ghimire, B. (Bishwa), Topa, H. (Hande), Kurki, M. I. (Mitja I.), Koskela, M. (Maryna), Airavaara, M. (Mikko), Hämäläinen, E. (Eija), Pylkäs, K. (Katri), Körkkö, J. (Jarmo), Savolainen, H. (Helena), Suoranta, A. (Anu), Bertoli-Avella, A. (Aida), Rolfs, A. (Arndt), Mattila, P. (Pirkko), Daly, M. (Mark), Palotie, A. (Aarno), Pietiläinen, O. (Olli), Moilanen, J. (Jukka), and Kuismin, O. (Outi)

Abstract

Biallelic loss-of-function variants in the SMG9 gene, encoding a regulatory subunit of the mRNA nonsense-mediated decay (NMD) machinery, are reported to cause heart and brain malformation syndrome. Here we report five patients from three unrelated families with intellectual disability (ID) and a novel pathogenic SMG9 c.551 T > C p.(Val184Ala) homozygous missense variant, identified using exome sequencing. Sanger sequencing confirmed recessive segregation in each family. SMG9 c.551T > C p.(Val184Ala) is most likely an autozygous variant identical by descent. Characteristic clinical findings in patients were mild to moderate ID, intention tremor, pyramidal signs, dyspraxia, and ocular manifestations. We used RNA sequencing of patients and age- and sex-matched healthy controls to assess the effect of the variant. RNA sequencing revealed that the SMG9 c.551T > C variant did not affect the splicing or expression level of SMG9 gene products, and allele-specific expression analysis did not provide evidence that the nonsense mRNA-induced NMD was affected. Differential gene expression analysis identified prevalent upregulation of genes in patients, including the genes SMOX, OSBP2, GPX3, and ZNF155. These findings suggest that normal SMG9 function may be involved in transcriptional regulation without affecting nonsense mRNA-induced NMD. In conclusion, we demonstrate that the SMG9 c.551T > C missense variant causes a neurodevelopmental disorder and impacts gene expression. NMD components have roles beyond aberrant mRNA degradation that are crucial for neurocognitive development.

Published
2022

7. Maternal postpartum depressive symptoms partially mediate the association between preterm birth and mental and behavioral disorders in children

Author

Girchenko, P. (Polina), Robinson, R. (Rachel), Rantalainen, V. J. (Ville Juhani), Lahti-Pulkkinen, M. (Marius), Heinonen-Tuomaala, K. (Kati), Lemola, S. (Sakari), Wolke, D. (Dieter), Schnitzlein, D. (Daniel), Hämäläinen, E. (Esa), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Kajantie, E. (Eero), Räikkönen, K. (Katri), Girchenko, P. (Polina), Robinson, R. (Rachel), Rantalainen, V. J. (Ville Juhani), Lahti-Pulkkinen, M. (Marius), Heinonen-Tuomaala, K. (Kati), Lemola, S. (Sakari), Wolke, D. (Dieter), Schnitzlein, D. (Daniel), Hämäläinen, E. (Esa), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Kajantie, E. (Eero), and Räikkönen, K. (Katri)

Abstract

Preterm birth has been linked with postpartum depressive (PPD) disorders and high symptom levels, but evidence remains conflicting and limited in quality. It remains unclear whether PPD symptoms of mothers with preterm babies were already elevated before childbirth, and whether PPD symptoms mediate/aggravate the effect of preterm birth on child mental disorders. We examined whether preterm birth associated with maternal PPD symptoms, depressive symptoms trajectories from antenatal to postpartum stage, and whether PPD symptoms mediated/aggravated associations between preterm birth and child mental disorders. Mothers of preterm (n = 125) and term-born (n = 3033) children of the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study reported depressive symptoms four times within 8 weeks before and twice within 12 months after childbirth. Child mental and behavioral disorder diagnoses until age 8.4–12.8 years came from medical register. Preterm birth associated with higher PPD symptoms (mean difference = 0.19 SD, 95% CI 0.01, 0.37, p = 0.04), and higher odds (odds ratio = 2.23, 95% CI 1.22, 4.09, p = 0.009) of the mother to belong to a group that had consistently high depressive symptoms levels trajectory from antenatal to postpartum stage. PPD symptoms partially mediated and aggravated the association between preterm birth and child mental disorders. Preterm birth, maternal PPD symptoms and child mental disorders are associated, calling for timely prevention interventions.

Published
2022

8. Quantitative urine proteomics in pregnant women for the identification of predictive biomarkers for preeclampsia

Author

Joenväärä, S. (Sakari), Holm, M. (Matilda), Saraswat, M. (Mayank), Agarwal, R. (Rahul), Tohmola, T. (Tiialotta), Kajantie, E. (Eero), Räikkönen, K. (Katri), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Hämäläinen, E. (Esa), Renkonen, R. (Risto), Joenväärä, S. (Sakari), Holm, M. (Matilda), Saraswat, M. (Mayank), Agarwal, R. (Rahul), Tohmola, T. (Tiialotta), Kajantie, E. (Eero), Räikkönen, K. (Katri), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Hämäläinen, E. (Esa), and Renkonen, R. (Risto)

Abstract

Background: Preeclampsia (PE) is a life-threatening disease characterized by elevated blood pressure and proteinuria. Predictive biomarkers of PE are needed, especially those predicting PE in early pregnancy. The aim of this pilot study was to identify urine proteins that could be candidates for new non-invasive markers for PE. Methods: Urine samples at three time points of pregnancy (12–14, 18–20 and 26–28 weeks of gestation) were prospectively collected from high-risk women who subsequently developed PE (n = 7), high-risk women who did not develop PE (n = 6), and women without known risk factors for PE (n = 4). The samples were analyzed using mass spectrometry and we subsequently quantified 361 proteins used for further analysis. Rigorous statistical analysis with multiple methods was performed to identify biomarker candidates. Results: Of the clinical risk factors analyzed, pre-pregnancy body mass index (BMIBP) was found to be the most important predictor of PE. We identified multiple proteins that correlated with BMIBP and could improve the prediction of PE in combination with BMIBP. Other statistical analyses identified six proteins that each could differentiate women who subsequently developed PE from those who did not at all three time points. Conclusions: We identified multiple urine proteins that could be used to predict PE in combination with BMIBP. We also identified six proteins that are strong candidates for predicting PE already in early pregnancy.

Published
2022

14. Wir wollen die biologische Vielfalt schützen:eine sprachwissenschaftlich-funktionale Analyse über das Thema Nachhaltigkeit auf der Plattform thisisFINLAND

Author

Hämäläinen, E. (Ella)

Abstract

Nachhaltigkeit ist weltweit ein aktuelles Thema, das mittlerweile Mainstream geworden ist und deswegen als Thema der Arbeit gewählt wurde. Die Hypothese ist, dass die Artikel appellierende Funktion, die normalerweise charakteristisch für klassische Werbung ist, neben der informativen Funktion haben. Das Ziel dieser Arbeit ist durch eine sprachwissenschaftlich-funktionale Analyse herauszufinden, wie über das Thema Nachhaltigkeit in der Plattform thisisFINLAND kommuniziert wird und wie damit geworben wird, wenn überhaupt. Die Forschungsfragen der Arbeit sind folgende: Wie wird das Thema ‚Nachhaltigkeit‘ in den Texten der Plattform finland.fi versprachlicht? Wird das Thema ‚Nachhaltigkeit‘ beworben? Das Material dieser Arbeit besteht aus den fünf jüngsten deutschsprachigen Artikeln vom Oktober 2019 der Plattform thisisFINLAND, die vom Thema Nachhaltigkeit handeln. Als Methode dieser Arbeit wird die Lasswell-Formel verwendet, die ein einfaches Kommunikationsmodell ist. Die Formel lautent folgendermaßen: Wer sagt was in welchem Kanal zu wem mit welchem Effekt? Die untersuchten Aspekte Sender, Nachhaltigkeit als Thema, Zielgruppe und Funktion sind aufgrund dieser Formel gebildet worden. Aufgrund der Analyse zeigt sich, dass die Sender, also Finnland und die finnische Bevölkerung, vielseitig über die Sache, die im Zusammenhang mit Nachhaltigkeit stehen, zu zwei verschiedenen deutschsprachigen Zielgruppen, bzw. Touristen und Unternehmen, kommunizieren. Das Thema Nachhaltigkeit wird vielseitig in den Texten versprachlicht: Drei Dimensionen der Nachhaltigkeit kommen klar in den Texten durch verschiedene Wortfelder zum Ausdruck. Man kann sagen, dass die Hypothese der Arbeit richtig war: Das Thema Nachhaltigkeit wird beworben. Die Texte haben neben der informativen Funktion viele Merkmale der appellierende Funktion, die charakteristisch für die klassische Werbung ist. Weitere mögliche Forschung kann z.B. ein Vergleich von deutsch- und englischsprachigen Artikeln der Plattform thisisFINLAND über Nachhaltigkeit oder die Untersuchung der Visualisierung sein.

Published
2020

15. Longitudinal metabolic profiling of maternal obesity, gestational diabetes, and hypertensive pregnancy disorders

Author

Kivelä, J. (Jemina), Sormunen-Harju, H. (Heidi), Girchenko, P. V. (Polina V.), Huvinen, E. (Emilia), Stach-Lempinen, B. (Beata), Kajantie, E. (Eero), Villa, P. M. (Pia M.), Reynolds, R. M. (Rebecca M.), Hämäläinen, E. K. (Esa K.), Lahti-Pulkkinen, M. (Marius), Murtoniemi, K. K. (Katja K.), Laivuori, H. (Hannele), Eriksson, J. G. (Johan G.), Räikkönen, K. (Katri), Koivusalo, S. B. (Saila B.), Kivelä, J. (Jemina), Sormunen-Harju, H. (Heidi), Girchenko, P. V. (Polina V.), Huvinen, E. (Emilia), Stach-Lempinen, B. (Beata), Kajantie, E. (Eero), Villa, P. M. (Pia M.), Reynolds, R. M. (Rebecca M.), Hämäläinen, E. K. (Esa K.), Lahti-Pulkkinen, M. (Marius), Murtoniemi, K. K. (Katja K.), Laivuori, H. (Hannele), Eriksson, J. G. (Johan G.), Räikkönen, K. (Katri), and Koivusalo, S. B. (Saila B.)

Abstract

Context: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden. Objective: To assess levels, profiles, and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM), or hypertensive disorders. Design, Setting and Participant: A secondary analysis of 2 study cohorts, PREDO and RADIEL, including 741 pregnant women. Main Outcome Measures: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 [interquartile range (IQR) 12.4–13.7], 20 (IQR 19.3–23.0), and 28 (27.0–35.0) weeks of gestation. Results: Across all 3 time points women with obesity [body mass index (BMI) ≥ 30kg/m²] in comparison to normal weight (BMI 18.5–24.99 kg/m²) had significantly higher levels of most very-low-density lipoprotein-related measures, many fatty and most amino acids, and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia, and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered nonsignificant after adjustment for BMI and the other pregnancy disorders. Conclusions: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.

Published
2021

16. Maternal depression and inflammation during pregnancy

Author

Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Robinson, R. (Rachel), Lehto, S. M. (Soili M.), Toffol, E. (Elena), Heinonen, K. (Kati), Reynolds, R. M. (Rebecca M.), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Hämäläinen, E. (Esa), Lahti, J. (Jari), Räikkönen, K. (Katri), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Robinson, R. (Rachel), Lehto, S. M. (Soili M.), Toffol, E. (Elena), Heinonen, K. (Kati), Reynolds, R. M. (Rebecca M.), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Hämäläinen, E. (Esa), Lahti, J. (Jari), and Räikkönen, K. (Katri)

Abstract

Background: Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions. Methods: We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records. Results: Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26–1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17–0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00–0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12–0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction). Conclusions: Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early

Published
2021

17. Serum inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women

Author

Keikkala, E. (Elina), Forstén, J. (Janina), Ritvos, O. (Olli), Stenman, U.-H. (Ulf-Håkan), Kajantie, E. (Eero), Hämäläinen, E. (Esa), Räikkönen, K. (Katri), Villa, P. M. (Pia M.), Laivuori, H. (Hannele), Keikkala, E. (Elina), Forstén, J. (Janina), Ritvos, O. (Olli), Stenman, U.-H. (Ulf-Håkan), Kajantie, E. (Eero), Hämäläinen, E. (Esa), Räikkönen, K. (Katri), Villa, P. M. (Pia M.), and Laivuori, H. (Hannele)

Abstract

Objectives: Maternal serum inhibin-A, pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine artery pulsatility index (UtA PI) were analysed to study their ability to predict pre-eclampsia (PE). Study design: Serial serum samples for the nested case-control study were collected prospectively at 12–14, 18–20 and 26–28 weeks of gestation from 11 women who later developed early-onset PE (EO PE, diagnosis < 34 + 0 weeks of gestation), 34 women who developed late-onset PE (LO PE, diagnosis ≥ 34 + 0 weeks) and 89 controls. Main outcome measures: Gestational age -adjusted multiples of the median (MoM) values were calculated for biomarker concentrations. Multivariate regression analyses were performed to combine first trimester biomarkers, previously reported results on PlGF, maternal risk factors and UtA PI. Area under curve (AUC) values and 95% confidence intervals (CIs) for the prediction of PE and its subtypes were calculated. Results: A high first trimester inhibin-A predicted PE (AUC 0.618, 95%CI, 0.513–0.724), whereas PAPP-A and PlGF predicted only EO PE (0.701, 0.562–0.840 and 0.798, 0.686–0.909, respectively). At 26–28 weeks PAPP-A2 and inhibin-A predicted all PE subtypes. In the multivariate setting inhibin-A combined with maternal pre-pregnancy body mass index, prior PE and mean UtA PI predicted PE (0.811,0.726–0.896) and LO PE (0.824, 0.733–0.914). Conclusions: At first trimester inhibin-A show potential ability to predict not only EO PE but also LO PE whereas PlGF and PAPP-A predict only EO PE. At late second trimester inhibin-A and PAPP-A2 might be useful for short-term prediction of PE.

Published
2021

18. Maternal antenatal stress and mental and behavioral disorders in their children

Author

Tuovinen, S. (Soile), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Heinonen, K. (Kati), Lahti, J. (Jari), Reynolds, R. M. (Rebecca M.), Hämäläinen, E. (Esa), Villa, P. M. (Pia M.), Kajantie, E. (Eero), Laivuori, H. (Hannele), Raikkonen, K. (Katri), Tuovinen, S. (Soile), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Heinonen, K. (Kati), Lahti, J. (Jari), Reynolds, R. M. (Rebecca M.), Hämäläinen, E. (Esa), Villa, P. M. (Pia M.), Kajantie, E. (Eero), Laivuori, H. (Hannele), and Raikkonen, K. (Katri)

Abstract

Background: Maternal antenatal stress, including symptoms of depression, anxiety and perceived stress, is associated with mental and behavioral problems in children. Whether it is associated with child mental and behavioral disorders remains uncertain. We examined if maternal antenatal symptoms of depression, anxiety and perceived stress were associated with mental and behavioral disorders in their children, if the associations varied according to gestational week, stress type, fluctuating or consistently high symptoms, and if they were driven by maternal or paternal lifetime mood or anxiety disorders. Methods: 3365 mothers participating in the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiologic Studies Depression Scale, the State Anxiety Inventory and the Perceived Stress Scale up to 14 times throughout pregnancy. The Care Register for Health Care provided data on mental and behavioral (including neurodevelopmental) disorders for their children from birth (11/07/2006–07/24/2010) until 12/31/2016 and for parental lifetime mood and anxiety disorders until 12/31/2016. Results: The hazard of any childhood mental and behavioral disorder (HR=1.91, 95% CI: 1.39–2.51) was significantly higher for children whose mothers reported consistently high in comparison to consistently low levels of all types of stress throughout pregnancy. The associations remained significant when adjusted for maternal and paternal lifetime mood and anxiety disorders (and their comorbidity and timing and mood disorder type). Conclusions: Maternal antenatal stress is associated with higher risk of childhood mental and behavioral disorders. Efforts to reduce maternal antenatal stress should be given a high priority to improve child mental health.

Published
2021

26. A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders

Author

Suarez, A. (Anna), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Czamara, D. (Darina), Arloth, J. (Janine), Malmberg, A. L. (Anni LK.), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Reynolds, R. M. (Rebecca M.), Provençal, N. (Nadine), Binder, E. B. (Elisabeth B.), and Räikkönen, K. (Katri)

Subjects
Cord blood methylation, Childhood mental health, Polyepigenetic biomarker, Prospective study, Glucocorticoids, Prenatal psychopathology
Abstract

Background: Maternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes. Methods: Children (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child’s age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583). Results: The fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p < 0.001) more days in inpatient or outpatient treatment with any mental and behavioral disorder as the primary diagnosis. Criteria for mediation tests were not met. Conclusions: These findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders.

Published
2020

27. Black carbon, maritime traffic and the Arctic

Author

Brunila, O.-P. (Olli-Pekka), Inkinen, T. (Tommi), Hämäläinen, E. (Esa), Kunnaala-Hyrkki, V. (Vappu), and Ala-Rämi, K. (Katariina)

Subjects
Black carbon, Arctic, Ship traffic, Emission abatement
Abstract

Maritime transportation covers approximately 90% of the global traffic volumes. The global fleet consists of approximately 100,000 diesel ships, around 250 LNG ships, and a smaller number of methanol or even electric ferries. When it comes to maritime transportation, the Arctic sea route is becoming more and more interesting for the shipping industry as it has been estimated that the Northeast Passage can shorten the travelling distance significantly compared to Suez Canal. Black Carbon (BC) is the second largest contributor to climate change emissions after carbon dioxide (CO₂). BC particles spread out from different sources and the majority of BC emissions are transmitted to the Polar Regions from other parts of the globe. The share of global BC emission from international shipping is estimated to be up to 3% of the global total. The Northern Sea Route can shorten the travelling distance, but it is important to find out, will the increase of maritime traffic effect the BC emissions in the Arctic. This paper considers how BC from ships’ fuel affects the Arctic. This paper also discusses alternative fuels and emission abatement technologies, which can decrease the emissions from ships and may also affect the BC emissions in the Arctic in the future.

Published
2020

33. Associations of antenatal glucocorticoid exposure with mental health in children

Author

Wolford, E. (Elina), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Lipsanen, J. (Jari), Tuovinen, S. (Soile), Lahti, J. (Jari), Heinonen, K. (Kati), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Pesonen, A.-K. (Anu-Katriina), Villa, P. M. (Pia M), Laivuori, H. (Hannele), Reynolds, R. M. (Rebecca M), Räikkönen, K. (Katri), Wolford, E. (Elina), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Lipsanen, J. (Jari), Tuovinen, S. (Soile), Lahti, J. (Jari), Heinonen, K. (Kati), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Pesonen, A.-K. (Anu-Katriina), Villa, P. M. (Pia M), Laivuori, H. (Hannele), Reynolds, R. M. (Rebecca M), and Räikkönen, K. (Katri)

Abstract

Background: Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children. Methods: We included 4708 women and their children, born 2006–2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child’s birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age. Results: Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76–4.32), 3.61 (2.19–5.95), 3.29 (1.86–5.82), and 6.04 (3.25–11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children. Conclusions: Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.

Published
2020

34. Cerebral small vessel disease genomics and its implications across the lifespan

Author

Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), Debette, S. (Stéphanie), Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), and Debette, S. (Stéphanie)

Abstract

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Published
2020
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35. A genome-wide cross-phenotype meta-analysis of the association of blood pressure with migraine

Author

Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), Chasman, D.I. (Daniel), Guo, Y. (Yanjun), Rist, P.M. (Pamela M.), Daghlas, I. (Iyas), Giulianini, F. (Franco), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tonu), Pers, T.H. (Tune H.), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), McMahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.D. (Scott D.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H. H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Hrafnsdottir, M.G. (Maria Gudlaug), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda W. J. H.), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T. (Thomas), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn M. J. M. van den), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark J.), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel I.), Nyholt, D.R. (Dale R.), Palotie, A. (Aarno), Agee, M. (Michelle), Auton, A. (Adam), Bell, R.K. (Robert K.), Bryc, K. (Katarzyna), Elson, S.L. (Sarah L.), Fontanillas, P. (Pierre), Huber, K.E. (Karen E.), Kleinman, A. (Aaron), Litterman, N.K. (Nadia K.), McCreight, J.C. (Jennifer C.), McIntyre, M.H. (Matthew H.), Mountain, J.L. (Joanna L.), Noblin, E.S. (Elizabeth S.), Northover, C.A.M. (Carrie A. M.), Pitts, S.J. (Steven J.), Sathirapongsasuti, J.F. (J. Fah), Sazonova, O.V. (Olga V.), Shelton, J.F. (Janie F.), Shringarpure, S. (Suyash), Tian, C. (Chao), Tung, J.Y. (Joyce Y.), Vacic, V. (Vladimir), Kurth, K.H. (Karl), and Chasman, D.I. (Daniel)

Abstract

Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3.56 × 10−06) and systolic BP (SBP, rg = 0.06, P = 0.01), but not pulse pressure (PP, rg = −0.01, P = 0.75). Cross-trait meta-analysis reveals 14 shared loci (P ≤ 5 × 10−08), nine of which replicate (P < 0.05) in the UK Biobank. Five shared loci (ITGB5, SMG6, ADRA2B, ANKDD1B, and KIAA0040) are reinforced in gene-level analysis and highlight potential mechanisms involving vascular development, endothelial function and calcium homeostasis. Mendelian randomization reveals stronger instrumental estimates of DBP (OR [95% CI] = 1.20 [1.15–1.25]/10 mmHg; P = 5.57 × 10−25) on migraine than SBP (1.05 [1.03–1.07]/10 mmHg; P = 2.60 × 10−07) and a corresponding opposite effect for PP (0.92 [0.88–0.95]/10 mmHg; P = 3.65 × 10−07). These findings support a critical role of DBP in migraine susceptibility and shared biology underlying BP and migraine.

Published
2020
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36. Cord blood DNA methylation reflects cord blood C-reactive protein levels but not maternal levels: a longitudinal study and meta-analysis

Author

Yeung, E.H. (Edwina H.), Guan, W. (Weihua), Zeng, X. (Xuehuo), Salas, L.A. (Lucas A.), Mumford, S.L. (Sunni L.), de Prado Bert, P. (Paula), Meel, E.R. (Evelien) van, Malmberg, A. (Anni), Sunyer, J. (Jordi), Duijts, L. (Liesbeth), Felix, J.F. (Janine), Czamara, D. (Darina), Hämäläinen, E. (Esa), Binder, E.B. (Elisabeth), Räikkönen, K. (Katri), Lahti, J. (Jari), London, S.J. (Stephanie J.), Silver, R.M. (Robert M.), Schisterman, E.F. (Enrique F.), Yeung, E.H. (Edwina H.), Guan, W. (Weihua), Zeng, X. (Xuehuo), Salas, L.A. (Lucas A.), Mumford, S.L. (Sunni L.), de Prado Bert, P. (Paula), Meel, E.R. (Evelien) van, Malmberg, A. (Anni), Sunyer, J. (Jordi), Duijts, L. (Liesbeth), Felix, J.F. (Janine), Czamara, D. (Darina), Hämäläinen, E. (Esa), Binder, E.B. (Elisabeth), Räikkönen, K. (Katri), Lahti, J. (Jari), London, S.J. (Stephanie J.), Silver, R.M. (Robert M.), and Schisterman, E.F. (Enrique F.)

Abstract

BACKGROUND: Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. RESULTS: Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in cord blood. The t

Published
2020
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37. Polygenic prediction of the risk of perinatal depressive symptoms

Author

Rantalainen, V. (Ville), Binder, E. B. (Elisabeth B.), Lahti‐Pulkkinen, M. (Marius), Czamara, D. (Darina), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Girchenko, P. (Polina), Kvist, T. (Tuomas), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Lahti, J. (Jari), Räikkönen, K. (Katri), Rantalainen, V. (Ville), Binder, E. B. (Elisabeth B.), Lahti‐Pulkkinen, M. (Marius), Czamara, D. (Darina), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Girchenko, P. (Polina), Kvist, T. (Tuomas), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Lahti, J. (Jari), and Räikkönen, K. (Katri)

Abstract

Background: Perinatal depression carries adverse effects on maternal health and child development, but genetic underpinnings remain unclear. We investigated the polygenic risk of perinatal depressive symptoms. Methods: About 742 women from the prospective Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction cohort were genotyped and completed the Center for Epidemiologic Studies Depression scale 14 times during the prenatal period and twice up to 12 months postpartum. Polygenic risk scores for major depressive disorder, bipolar disorder, schizophrenia, and cross-disorder were calculated using multiple p-value thresholds. Results: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder, but not bipolar disorder, were associated with higher prenatal and postpartum depressive symptoms (0.8%–1% increase per one standard deviation increase in polygenic risk scores). Prenatal depressive symptoms accounted for and mediated the associations between the polygenic risk scores and postpartum depressive symptoms (effect size proportions-mediated: 52.2%–88.0%). Further, the polygenic risk scores were associated with 1.24–1.45-fold odds to belong to the group displaying consistently high compared with consistently low depressive symptoms through out the prenatal and postpartum periods. Conclusions: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder in non-perinatal populations generalize to perinatal depressive symptoms and may afford to identify women for timely preventive interventions.

Published
2020

38. Persistently high levels of maternal antenatal inflammation are associated with and mediate the effect of prenatal environmental adversities on neurodevelopmental delay in the offspring

Author

Girchenko, P. (Polina), Lahti-Pulkkinen, M. (Marius), Heinonen, K. (Kati), Reynolds, R. M. (Rebecca M.), Laivuori, H. (Hannele), Lipsanen, J. (Jari), Villa, P. M. (Pia M.), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Lahti, J. (Jari), Räikkönen, K. (Katri), Girchenko, P. (Polina), Lahti-Pulkkinen, M. (Marius), Heinonen, K. (Kati), Reynolds, R. M. (Rebecca M.), Laivuori, H. (Hannele), Lipsanen, J. (Jari), Villa, P. M. (Pia M.), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Lahti, J. (Jari), and Räikkönen, K. (Katri)

Abstract

Background: Prenatal exposure to environmental adversities, including maternal overweight/obesity, diabetes/hypertensive disorders, or mood/anxiety disorders, increases the risk for adverse neurodevelopmental outcomes in children. However, the underlying biological mechanisms remain elusive. We tested whether maternal antenatal inflammation was associated with the number of neurodevelopmental delay areas in children and whether it mediated the association between exposure to any prenatal environmental adversity and child neurodevelopmental delay. Methods: Mother-child dyads (N = 418) from the PREDO (Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction) study were followed up to 10.8 years. We analyzed maternal plasma high-sensitivity C-reactive protein and glycoprotein acetyls at 3 consecutive antenatal time points, measured maternal body mass index in early pregnancy, extracted data on diabetes/hypertensive disorders in pregnancy from medical records, and extracted data on mood/anxiety disorders until childbirth from the Care Register for Health Care. To estimate the number of neurodevelopmental delay areas in children across cognitive, motor, and social functioning, we pooled data from the Care Register for Health Care on psychological development disorders with mother-reported Ages and Stages Questionnaire data on developmental milestones. Results: Higher levels of maternal high-sensitivity C-reactive protein and glycoprotein acetyls at and across all 3 antenatal time points were associated with 1.30- to 2.36-fold (p values < 0.02) increased relative risk for higher number of areas of child neurodevelopmental delay. Higher maternal inflammation across the 3 time points also mediated the effect of any prenatal environmental adversity on child neurodevelopmental delay. Conclusions: Higher levels of maternal inflammation, especially when persisting throughout pregnancy, increase a child’s risk of neurodevelopmental delay and medi

Published
2020

39. Maternal hypertensive pregnancy disorders and mental disorders in children

Author

Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Tuovinen, S. (Soile), Sammallahti, S. (Sara), Reynolds, R. M. (Rebecca M.), Lahti, J. (Jari), Heinonen, K. (Kati), Lipsanen, J. (Jari), Hämäläinen, E. (Esa), Villa, P. M. (Pia M.), Kajantie, E. (Eero), Laivuori, H. (Hannele), Räikkönen, K. (Katri), Lahti-Pulkkinen, M. (Marius), Girchenko, P. (Polina), Tuovinen, S. (Soile), Sammallahti, S. (Sara), Reynolds, R. M. (Rebecca M.), Lahti, J. (Jari), Heinonen, K. (Kati), Lipsanen, J. (Jari), Hämäläinen, E. (Esa), Villa, P. M. (Pia M.), Kajantie, E. (Eero), Laivuori, H. (Hannele), and Räikkönen, K. (Katri)

Abstract

The associations of maternal hypertensive pregnancy disorders with offspring mental disorders remain unclear. We examined whether maternal hypertensive disorders and maximum blood pressure during pregnancy predict offspring childhood mental disorders, whether the associations are independent of maternal and paternal mental disorders and paternal hypertensive disorders, independent of or additive with maternal early pregnancy overweight/obesity and diabetes mellitus disorders, and mediated or moderated by preterm birth, small-for-gestational-age birth and neonatal intensive care unit admission. Our prospective study comprised 4743 mother-child dyads of Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction study. Women were recruited to the study in early pregnancy at Finnish maternity hospitals. Children were born 2006 to 2010 and followed-up until December 31, 2016, to ages 6.4 to 10.8 years. Hypertensive pregnancy disorders were identified from medical records, Medical Birth Register, and Care Register for Health Care. Systolic and diastolic blood pressure were measured at antenatal clinics and hospital visits. Mental disorder diagnoses were identified from Care Register for Health Care. Maternal gestational and chronic hypertension, preeclampsia and its severity increased offspring hazard of any childhood mental disorder. The associations of preeclampsia (hazard ratio=1.66 [95% CI, 1.14–2.42]) and severe preeclampsia (hazard ratio=2.01 [95% CI, 1.08–3.73]) were independent of all covariates. Maternal hypertensive and diabetes mellitus disorders and overweight/obesity also additively increased offspring hazard of mental disorders. Preterm and small-for-gestational-age births and neonatal intensive care unit admission partially mediated the effects of any and severe preeclampsia on offspring mental disorders. To conclude, maternal hypertensive pregnancy disorders carry adverse consequences for offspring mental health.

Published
2020

40. Plasma pentraxin 3 is higher in early ovarian hyperstimulation syndrome than in uncomplicated in vitro fertilization cycle of high-risk women

Author

Korhonen, K. (Kati), Unkila-Kallio, L. (Leila), Alfthan, H. (Henrik), Hämäläinen, E. (Esa), Tiitinen, A. (Aila), Mikkola, T. (Tomi), Tapanainen, J. (Juha), Savolainen-Peltonen, H. (Hanna), Korhonen, K. (Kati), Unkila-Kallio, L. (Leila), Alfthan, H. (Henrik), Hämäläinen, E. (Esa), Tiitinen, A. (Aila), Mikkola, T. (Tomi), Tapanainen, J. (Juha), and Savolainen-Peltonen, H. (Hanna)

Abstract

Purpose: Pentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF). Methods: This two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC). Results: The circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15–20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level. Conclusion: The elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS.

Published
2020

42. Migraine without aura: genome-wide association analysis identifies several novel susceptibility

Author

De Vries, B Loci, Freilinger, T, Anttila, V, Malik, R, Terwindt, GM, Pozo-Rosich, P, Winsvold, B, Nyholt, D, van Oosterhout, WPJ, Artto, V, Todt, M, Hämäläinen, E, Fernandez-Moralez, J, Louter, M, Kaunisto, MA, Schoenen, J, Raitakari, O, Lehtimäki, T, Ville-Pueyo, M, Göbel, H, Wichman, E, Sintas, C, Uitterlinden, A, Hofman, A, Rivadeneira, F, Heinze, A, Tronvik, E, van Duin, CM, Kaprio, J, Cormand, B, Wessman, M, Frants, RR, Meitinger, T, Müller-Myhsok, B, Zwart, JA, Färkkilä, M, Macaya, A, Ferrari, MD, Kubisch, C, Palotie, A, Dichgans, M, and van den Maagdenberg, AMJ

Published
2013
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43. Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Author

Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J.A. (James A), Kohane, I.S., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Smoller, J.W., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), Binder, E.B. (Elisabeth), Czamara, D. (Darina), Eraslan, G. (Gökçen), Page, C.M. (Christian M.), Lahti, J. (Jari), Lahti-Pulkkinen, M. (Marius), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P.M. (Pia M.), Reynolds, R.M. (Rebecca M.), Nystad, W. (Wenche), Håberg, S.E. (Siri E), London, S.J. (Stephanie J.), O’Donnell, K.J. (Kieran J.), Garg, E. (Elika), Meaney, M.J., Entringer, S., Wadhwa, P.D. (Pathik D.), Buss, C. (Claudia), Jones, M.J. (Meaghan J.), Lin, D.T.S. (David T. S.), MacIsaac, J.L. (Julie L.), Kobor, M.S. (Michael S.), Koen, N. (Nastassja), Zar, H.J., Koenen, M.E. (Marjorie), Dalvie, S. (Shareefa), Stein, D.J. (Dan), Kondofersky, I. (Ivan), Müller, N.S. (Nikola S.), Theis, F. (Fabian), Wray, N.R. (Naomi), Ripke, S. (Stephan), Mattheisen, M. (Manuel), Trzaskowski, M. (Maciej), Byrne, E.M. (Enda), Abdellaoui, A. (Abdel), Adams, M.J. (Mark J.), Agerbo, E. (Esben), Air, T.M. (Tracy M.), Andlauer, T.F.M. (Till F. M.), Bacanu, S.A. (Silviu), Bækvad-Hansen, M. (Marie), Beekman, A.T.F. (Aartjan), Bigdeli, T.B. (Tim B.), Blackwood, D.H.R. (Douglas), Bryois, J. (Julien), Buttenschøn, H.N. (Henriette N.), Bybjerg-Grauholm, J. (Jonas), Cai, N. (Na), Castelao, E. (Enrique), Christensen, J.H. (Jane Hvarregaard), Clarke, T.-K., Coleman, J.R.I. (Jonathan R. I.), Colodro-Conde, L. (Lucía), Couvy-Duchesne, B. (Baptiste), Craddock, N.J. (Nick), Crawford, G.E. (Gregory E.), Davies, G. (Gail), Deary, I.J. (Ian), Degenhardt, F., Derks, E.M. (Eske), Direk, N. (Nese), Dolan, C.V. (Conor), Dunn, E.C. (Erin C.), Eley, T.C. (T.), Escott-Price, V. (Valentina), Kiadeh, F.F.H. (Farnush Farhadi Hassan), Finucane, H.K. (Hilary K.), Forstner, A.J. (Andreas J.), Frank, J. (Josef), Gaspar, H.A. (Héléna A.), Gill, M. (Michael), Goes, F.S. (Fernando S.), Gordon, S.D. (Scott D.), Grove, J. (Jakob), Hall, L.S. (Lynsey S.), Hansen, C.S. (Christine Søholm), Hansen, T.F. (Thomas F.), Herms, S. (Stefan), Hickie, I.B. (Ian), Hoffmann, P. (Per), Homuth, G. (Georg), Horn, C. (Carsten), Hottenga, J.J. (Jouke Jan), Hougaard, D.M. (David M.), Ising, M. (Marcus), Jansen, R. (Rick), Jorgenson, E. (Eric), Knowles, J.A. (James A), Kohane, I.S., Kraft, J. (Julia), Kretzschmar, W.W. (Warren W.), Krogh, J. (Jesper), Kutalik, Z. (Zoltán), Li, Y. (Yihan), Lind, P.A. (Penelope), Macintyre, D.J. (Donald J), MacKinnon, D.F. (Dean F.), Maier, R.M. (Robert M.), Maier, W. (Wolfgang), Marchini, J. (Jonathan), Mbarek, H., McGrath, P. (Patrick), McGuffin, P. (Peter), Medland, S.E. (Sarah), Mehta, D. (Divya), Middeldorp, C.M. (Christel), Mihailov, E. (Evelin), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mondimore, F.M. (Francis M.), Montgomery, G.W. (Grant), Mostafavi, S. (Sara), Mullins, N. (Niamh), Nauck, M. (Matthias), Ng, B. (Bernard), Nivard, M. (Michel), Nyholt, D.R. (Dale), O’Reilly, P.F. (Paul F.), Oskarsson, H. (Hogni), Owen, M.J. (Michael J.), Painter, J.N. (Jodie N.), Pedersen, C.B. (C.), Pedersen, M.G. (Marianne Giørtz), Peterson, R.E. (Roseann E.), Pettersson, E. (Erik), Peyrot, W.J. (Wouter ), Pistis, G. (Giorgio), Posthuma, D. (Danielle), Quiroz, J.A. (Jorge A.), Qvist, P. (Per), Rice, J.P. (John), Riley, B.P. (Brien P.), Rivera, M. (Margarita), Mirza, S.S. (Saira), Schoevers, R. (Robert), Schulte, E.C. (Eva C.), Shen, L. (Ling), Shi, J. (Jianxin), Shyn, S.I. (Stanley I), Sigurdsson, E. (Engilbert), Sinnamon, G.C.B. (Grant C. B.), Smith, A.V. (Davey), Smith, D.J. (Daniel J.), Stefansson, H. (Hreinn), Steinberg, S. (Stacy), Streit, F. (Fabian), Strohmaier, J. (Jana), Tansey, K.E., Teismann, H. (Henning), Teumer, A. (Alexander), Thompson, W.K. (Wesley K.), Thomson, P.A. (Pippa A.), Thorgeirsson, T.E. (Thorgeir E.), Traylor, M. (Matthew), Treutlein, J. (Jens), Trubetskoy, V. (Vassily), Uitterlinden, A.G. (André), Umbricht, D. (Daniel), Van der Auwera, S. (Sandra), van Hemert, A.M. (Albert M.), Viktorin, A. (Alexander), Visscher, P.M. (Peter M.), Wang, Y. (Yunpeng), Webb, B.T. (Bradley T.), Weinsheimer, S.M. (Shantel Marie), Wellmann, J. (Jürgen), Willemsen, G.A.H.M. (Gonneke), Witt, S.H. (Stephanie H), Wu, Y. (Yang), Xi, H.S. (Hualin S.), Yang, J. (Jian), Zhang, F. (Futao), Arolt, V. (Volker), Baune, B.T., Berger, K. (Klaus), Boomsma, D.I. (Dorret), Cichon, S. (Sven), Dannlowski, U. (Udo), Geus, E.J.C. (Eco) de, DePaulo, J.R. (J. Raymond), Domenici, E. (Enrico), Domschke, K. (Katharina), Esko, T. (Tõnu), Grabe, H.J. (Hans Jörgen), Hamilton, S.P. (Steven P), Hayward, C. (Caroline), Heath, A.C. (Andrew), Jablensky, A. (Assen), Kloiber, S. (Stefan), Lewis, G., Li, Q.S. (Qingqin S.), Lucae, S. (Susanne), Madden, P.A. (Pamela), Magnusson, P.K. (Patrik K.), Martin, N.G. (Nicholas), McIntosh, A.M. (Andrew M.), Metspalu, A. (Andres), Mors, O. (Ole), Mortensen, P.B. (Preben Bo), Müller-Myhsok, B. (B.), Nordentoft, M. (Merete), Nöthen, M.M. (Markus), O’Donovan, M.C. (Michael C.), Paciga, S.A. (Sara A.), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perlis, R.H. (Roy H), Porteous, D.J. (David J.), Potash, J.B. (James B), Preisig, M. (Martin), Rietschel, M. (Marcella), Schaefer, C. (Catherine), Schulze, T.G. (Thomas G.), Smoller, J.W., Stefansson, K. (Kari), Tiemeier, H.W. (Henning), Uher, R. (Rudolf), Völzke, H. (Henry), Weissman, M.M., Werge, T. (Thomas), Lewis, C.M. (Cathryn), Levinson, D.F. (Douglas F.), Breen, G. (Gerome), Borglum, A.D. (Anders), Sullivan, P.F. (Patrick F.), Räikkönen, K. (Katri), and Binder, E.B. (Elisabeth)

Abstract

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Published
2019
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44. Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Author

Küpers, LK, Monnereau, C, Sharp, GC, Yousefi, P, Salas, LA, Ghantous, A, Page, CM, Reese, SE, Wilcox, AJ, Czamara, D, Starling, AP, Novoloaca, A, Lent, S, Roy, R, Hoyo, C, Breton, CV, Allard, C, Just, AC, Bakulski, KM, Holloway, JW, Everson, TM, Xu, C-J, Huang, R-C, van der Plaat, DA, Wielscher, M, Merid, SK, Ullemar, V, Rezwan, FI, Lahti, J, van Dongen, J, Langie, SAS, Richardson, TG, Magnus, MC, Nohr, EA, Xu, Z, Duijts, L, Zhao, S, Zhang, W, Plusquin, M, DeMeo, DL, Solomon, O, Heimovaara, JH, Jima, DD, Gao, L, Bustamante, M, Perron, P, Wright, RO, Hertz-Picciotto, I, Zhang, H, Karagas, MR, Gehring, U, Marsit, CJ, Beilin, LJ, Vonk, JM, Jarvelin, M-R, Bergström, A, Örtqvist, AK, Ewart, S, Villa, PM, Moore, SE, Willemsen, G, Standaert, ARL, Håberg, SE, Sørensen, TIA, Taylor, JA, Räikkönen, K, Yang, IV, Kechris, K, Nawrot, TS, Silver, MJ, Gong, YY, Richiardi, L, Kogevinas, M, Litonjua, AA, Eskenazi, B, Huen, K, Mbarek, H, Maguire, RL, Dwyer, T, Vrijheid, M, Bouchard, L, Baccarelli, AA, Croen, LA, Karmaus, W, Anderson, D, de Vries, M, Sebert, S, Kere, J, Karlsson, R, Arshad, SH, Hämäläinen, E, Routledge, MN, Boomsma, DI, Feinberg, AP, Newschaffer, CJ, Govarts, E, Moisse, M, Fallin, MD, Melén, E, Prentice, AM, Kajantie, E, Almqvist, C, Oken, E, Dabelea, D, Boezen, HM, Melton, PE, Wright, RJ, Koppelman, GH, Trevisi, L, Hivert, M-F, Sunyer, J, Munthe-Kaas, MC, Murphy, SK, Corpeleijn, E, Wiemels, J, Holland, N, Herceg, Z, Binder, EB, Davey Smith, G, Jaddoe, VWV, Lie, RT, Nystad, W, London, SJ, Lawlor, DA, Relton, CL, Snieder, H, Felix, JF, Küpers, LK, Monnereau, C, Sharp, GC, Yousefi, P, Salas, LA, Ghantous, A, Page, CM, Reese, SE, Wilcox, AJ, Czamara, D, Starling, AP, Novoloaca, A, Lent, S, Roy, R, Hoyo, C, Breton, CV, Allard, C, Just, AC, Bakulski, KM, Holloway, JW, Everson, TM, Xu, C-J, Huang, R-C, van der Plaat, DA, Wielscher, M, Merid, SK, Ullemar, V, Rezwan, FI, Lahti, J, van Dongen, J, Langie, SAS, Richardson, TG, Magnus, MC, Nohr, EA, Xu, Z, Duijts, L, Zhao, S, Zhang, W, Plusquin, M, DeMeo, DL, Solomon, O, Heimovaara, JH, Jima, DD, Gao, L, Bustamante, M, Perron, P, Wright, RO, Hertz-Picciotto, I, Zhang, H, Karagas, MR, Gehring, U, Marsit, CJ, Beilin, LJ, Vonk, JM, Jarvelin, M-R, Bergström, A, Örtqvist, AK, Ewart, S, Villa, PM, Moore, SE, Willemsen, G, Standaert, ARL, Håberg, SE, Sørensen, TIA, Taylor, JA, Räikkönen, K, Yang, IV, Kechris, K, Nawrot, TS, Silver, MJ, Gong, YY, Richiardi, L, Kogevinas, M, Litonjua, AA, Eskenazi, B, Huen, K, Mbarek, H, Maguire, RL, Dwyer, T, Vrijheid, M, Bouchard, L, Baccarelli, AA, Croen, LA, Karmaus, W, Anderson, D, de Vries, M, Sebert, S, Kere, J, Karlsson, R, Arshad, SH, Hämäläinen, E, Routledge, MN, Boomsma, DI, Feinberg, AP, Newschaffer, CJ, Govarts, E, Moisse, M, Fallin, MD, Melén, E, Prentice, AM, Kajantie, E, Almqvist, C, Oken, E, Dabelea, D, Boezen, HM, Melton, PE, Wright, RJ, Koppelman, GH, Trevisi, L, Hivert, M-F, Sunyer, J, Munthe-Kaas, MC, Murphy, SK, Corpeleijn, E, Wiemels, J, Holland, N, Herceg, Z, Binder, EB, Davey Smith, G, Jaddoe, VWV, Lie, RT, Nystad, W, London, SJ, Lawlor, DA, Relton, CL, Snieder, H, and Felix, JF

Abstract

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Published
2019

45. Null mutation in P4h-tm leads to decreased fear and anxiety and increased social behavior in mice

Author

Leinonen, H. (Henri), Koivisto, H. (Hennariikka), Lipponen, H.-R. (Henna-Riikka), Matilainen, A. (Anna), Salo, A. M. (Antti M.), Dimova, E. Y. (Elitsa Y.), Hämäläinen, E. (Elina), Stavén, S. (Saara), Miettinen, P. (Pasi), Myllyharju, J. (Johanna), Koivunen, P. (Peppi), Tanila, H. (Heikki), Leinonen, H. (Henri), Koivisto, H. (Hennariikka), Lipponen, H.-R. (Henna-Riikka), Matilainen, A. (Anna), Salo, A. M. (Antti M.), Dimova, E. Y. (Elitsa Y.), Hämäläinen, E. (Elina), Stavén, S. (Saara), Miettinen, P. (Pasi), Myllyharju, J. (Johanna), Koivunen, P. (Peppi), and Tanila, H. (Heikki)

Abstract

HIF prolyl 4-hydroxylases (HIF-P4Hs, also known as PHDs and EGLNs) are crucial enzymes that modulate the hypoxia inducible factor (HIF) response and help to maintain cellular oxygen homeostasis. This function is especially well-known for cytoplasmic or nuclear enzymes HIF-P4H-1–3 (PHDs 1–3, EGLNs 2, 1 and 3, respectively), but the physiological role is still obscure for a fourth suggested HIF-P4H, P4H-TM that is a transmembrane protein and resides in the endoplasmic reticulum. Recently however, both experimental and clinical evidence of the P4H-TM involvement in CNS physiology has emerged. In this study, we first investigated the expression pattern of P4H-TM in the mouse brain and found a remarkably selective abundance in brains areas that are involved in social behaviors and anxiety including amygdala, lateral septum and bed nucleus of stria terminalis. Next, we performed behavioral assays in P4h-tm−/− mice to investigate a possible phenotype associated to these brain areas. In locomotor activity tests, we found that P4h-tm−/− mice were significantly more active than their wild-type (WT) littermate mice, and habituation to test environment did not abolish this effect. Instead, spatial learning and memory seemed normal in P4h-tm−/− mice as assessed by Morris swim task. In several tests assessing anxiety and fear responses, P4h-tm−/− mice showed distinct courageousness, and they presented increased interaction towards fellow mice in social behavior tests. Most strikingly, P4h-tm−/− mice practically lacked behavioral despair response, a surrogate marker of depression, in forced swim and tail suspension tests. Instead, mutant mice of all other Hif-p4h isoforms lacked such a behavioral phenotype. In summary, this study presents a remarkable anatomy-physiology association between the brain expression of P4H-TM and the behavioral phenotype in P4h-tm−/− mice. Future studies will reveal whether P4H-TM may serve as a novel target for anti-depressant and anti-anxiety

Published
2019

46. Maternal depressive symptoms during and after pregnancy are associated with poorer sleep quantity and quality and sleep disorders in 3.5-year-old offspring

Author

Toffol, E. (Elena), Lahti-Pulkkinen, M. (Marius), Lahti, J. (Jari), Lipsanen, J. (Jari), Heinonen, K. (Kati), Pesonen, A.-K. (Anu-Katriina), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), Räikkönen, K. (Katri), Toffol, E. (Elena), Lahti-Pulkkinen, M. (Marius), Lahti, J. (Jari), Lipsanen, J. (Jari), Heinonen, K. (Kati), Pesonen, A.-K. (Anu-Katriina), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Laivuori, H. (Hannele), Villa, P. M. (Pia M.), and Räikkönen, K. (Katri)

Abstract

Objective: Maternal depressive symptoms during pregnancy have been associated with poor offspring sleep. Yet, it remains unknown whether depressive symptoms throughout pregnancy are more harmful to the child than depressive symptoms only during certain time periods in pregnancy, whether associations are specific to pregnancy stage, whether maternal symptomatology after pregnancy mediates or adds to the prenatal effects, and whether any effects are specific to some child sleep characteristics. Methods: A total of 2321 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Center for Epidemiological Studies Depression Scale biweekly between gestational weeks + days 12 + 0/13 + 6 and 38 + 0/39 + 6. At child’s mean age of 3.5 (standard deviation = 0.7) years, mothers completed the Beck Depression Inventory−II and answered questions on child sleep quantity and quality using the Brief Infant Sleep Questionnaire (BISQ) and sleep disorders using the Sleep Disturbance Scale for Children. Results: Maternal depressive symptoms showed high stability throughout pregnancy. Children of mothers with clinically significant symptomatology throughout pregnancy had shorter mother-rated sleep duration, longer sleep latency, higher odds for waking up two or more times during the night and for total and several specific sleep disorders. These associations were robust to covariates. However, maternal depressive symptoms at the child follow-up fully mediated the associations with sleep duration and awakenings, partially mediated those with sleep latency and disorders, and added to the effects on sleep disorders. Conclusion: Maternal depressive symptoms throughout pregnancy are associated with mother-rated child sleep quantity, quality, and disorders. Maternal depressive symptoms at child follow-up mediate and add to the prenatal adverse effects on child sleep characteristics.

Published
2019

47. Contribution of rare and common variants to intellectual disability in a sub-isolate of Northern Finland

Author

Kurki, M. I. (Mitja I.), Saarentaus, E. (Elmo), Pietiläinen, O. (Olli), Gormley, P. (Padhraig), Lal, D. (Dennis), Kerminen, S. (Sini), Torniainen-Holm, M. (Minna), Hämäläinen, E. (Eija), Rahikkala, E. (Elisa), Keski-Filppula, R. (Riikka), Rauhala, M. (Merja), Korpi-Heikkilä, S. (Satu), Komulainen–Ebrahim, J. (Jonna), Helander, H. (Heli), Vieira, P. (Päivi), Männikkö, M. (Minna), Peltonen, M. (Markku), Havulinna, A. S. (Aki S.), Salomaa, V. (Veikko), Pirinen, M. (Matti), Suvisaari, J. (Jaana), Moilanen, J. S. (Jukka S.), Körkkö, J. (Jarmo), Kuismin, O. (Outi), Daly, M. J. (Mark J.), Palotie, A. (Aarno), Kurki, M. I. (Mitja I.), Saarentaus, E. (Elmo), Pietiläinen, O. (Olli), Gormley, P. (Padhraig), Lal, D. (Dennis), Kerminen, S. (Sini), Torniainen-Holm, M. (Minna), Hämäläinen, E. (Eija), Rahikkala, E. (Elisa), Keski-Filppula, R. (Riikka), Rauhala, M. (Merja), Korpi-Heikkilä, S. (Satu), Komulainen–Ebrahim, J. (Jonna), Helander, H. (Heli), Vieira, P. (Päivi), Männikkö, M. (Minna), Peltonen, M. (Markku), Havulinna, A. S. (Aki S.), Salomaa, V. (Veikko), Pirinen, M. (Matti), Suvisaari, J. (Jaana), Moilanen, J. S. (Jukka S.), Körkkö, J. (Jarmo), Kuismin, O. (Outi), Daly, M. J. (Mark J.), and Palotie, A. (Aarno)

Abstract

The contribution of de novo variants in severe intellectual disability (ID) has been extensively studied whereas the genetics of mild ID has been less characterized. To elucidate the genetics of milder ID we studied 442 ID patients enriched for mild ID (>50%) from a population isolate of Finland. Using exome sequencing, we show that rare damaging variants in known ID genes are observed significantly more often in severe (27%) than in mild ID (13%) patients. We further observe a significant enrichment of functional variants in genes not yet associated with ID (OR: 2.1). We show that a common variant polygenic risk significantly contributes to ID. The heritability explained by polygenic risk score is the highest for educational attainment (EDU) in mild ID (2.2%) but lower for more severe ID (0.6%). Finally, we identify a Finland enriched homozygote variant in the CRADD ID associated gene.

Published
2019

48. Longitudinal changes in plasma hemopexin and alpha-1-microglobulin concentrations in women with and without clinical risk factors for pre-eclampsia

Author

Murtoniemi, K. (Katja), Kalapotharakos, G. (Grigorios), Vahlberg, T. (Tero), Räikkönen, K. (Katri), Kajantie, E. (Eero), Hämäläinen, E. (Esa), Åkerström, B. (Bo), Villa, P. M. (Pia M.), Hansson, S. R. (Stefan R.), Laivuori, H. (Hannele), Murtoniemi, K. (Katja), Kalapotharakos, G. (Grigorios), Vahlberg, T. (Tero), Räikkönen, K. (Katri), Kajantie, E. (Eero), Hämäläinen, E. (Esa), Åkerström, B. (Bo), Villa, P. M. (Pia M.), Hansson, S. R. (Stefan R.), and Laivuori, H. (Hannele)

Abstract

Recent studies have shown increased concentration of fetal hemoglobin (HbF) in pre-eclamptic women. Plasma hemopexin (Hpx) and alpha-1-microglobulin (A1M) are hemoglobin scavenger proteins that protect against toxic effects of free heme released in the hemoglobin degradation process. We used an enzyme-linked immunosorbent assay to analyze maternal plasma Hpx and A1M concentrations at 12–14, 18–20 and 26–28 weeks of gestation in three groups: 1) 51 women with a low risk for pre-eclampsia (LRW), 2) 49 women with a high risk for pre-eclampsia (PE) who did not develop PE (HRW) and 3) 42 women with a high risk for PE who developed PE (HRPE). The study had three aims: 1) to investigate whether longitudinal differences exist between study groups, 2) to examine if Hpx and A1M concentrations develop differently in pre-eclamptic women with small for gestational age (SGA) fetuses vs. pre-eclamptic women with appropriate for gestational age fetuses, and 3) to examine if longitudinal Hpx and A1M profiles differ by PE subtype (early-onset vs. late-onset and severe vs. non-severe PE). Repeated measures analysis of variance was used to analyze differences in Hpx and A1M concentrations between the groups. We found that the differences in longitudinal plasma Hpx and A1M concentrations in HRW compared to HRPE and to LRW may be associated with reduced risk of PE regardless of clinical risk factors. In women who developed PE, a high A1M concentration from midgestation to late second trimester was associated with SGA. There were no differences in longitudinal Hpx and A1M concentrations from first to late second trimester in high-risk women who developed early-onset or. late-onset PE or in women who developed severe or. non-severe PE.

Published
2019

49. Impact of obesity on angiogenic and inflammatory markers in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort

Author

Jääskeläinen, T. (Tiina), Heinonen, S. (Seppo), Hämäläinen, E. (Esa), Pulkki, K. (Kari), Romppanen, J. (Jarkko), Laivuori, H. (Hannele), F. (FINNPEC), Jääskeläinen, T. (Tiina), Heinonen, S. (Seppo), Hämäläinen, E. (Esa), Pulkki, K. (Kari), Romppanen, J. (Jarkko), Laivuori, H. (Hannele), and F. (FINNPEC)

Abstract

Background: While several studies have demonstrated that obesity increases the risk of pre-eclampsia (PE), the mechanisms have yet to be elucidated. We assessed the association between maternal/paternal obesity and PE and hypothesized that maternal body mass index (BMI) would be associated with an adverse inflammatory and angiogenic profile. High-sensitivity C-reactive protein (hs-CRP) and following serum angiogenic markers were determined: soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). Methods: Data on BMI were available from 1450 pregnant women with PE and 1065 without PE. Serum concentrations of hs-CRP and angiogenic markers were available from a subset at first and third trimesters. Results: Prepregnancy BMI was higher in the PE group than in controls (mean ± SD) 25.3 ± 5.2 vs. 24.1 ± 4,4, p < 0.001, adjusted for parity, mother’s age, and smoking status before pregnancy. Increased hs-CRP concentrations were observed in both PE and non-PE women similarly according to BMI category. In women with PE, a higher BMI was associated with lower sFlt-1 and sEng concentrations throughout the pregnancy (p = 0.004, p = 0.008, respectively). There were no differences in PlGF in PE women according to BMI. Conclusions: We confirmed increased pre-pregnancy BMI in women with PE. Enhanced inflammatory state was confirmed in all women with overweight/obesity. Partly paradoxically we observed that PE women with obesity had less disturbed levels of angiogenic markers than normal weight women with PE. This should be taken into account when angiogenic markers are used in PE prediction., FINNPEC Members Hannele Laivuori2,7,8,9 (2Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland, 7Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland, 8Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland, 9Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, Finland), Seppo Heinonen2 (2Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland), Eero Kajantie10,11,12 (10Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, 11Children’s Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland, 12PEDEGO Research Unit, MRC Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland), Juha Kere13,14,15 (13Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden, 14Molecular Neurology Research Program, University of Helsinki, Helsinki, Finland, 15Folkhälsan Institute of Genetics, Helsinki, Finland), Katja Kivinen16 (16Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK), Anneli Pouta13,17 (13Department of Biosciences and Nutrition, and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden, 17Department of Government Services, National Institute for Health and Welfare, Helsinki, Finland)

Published
2019

50. Infant regulatory behavior problems during first month of life and neurobehavioral outcomes in early childhood

Author

Toffol, E. (Elena), Rantalainen, V. (Ville), Lahti‑Pulkkinen, M. (Marius), Girchenko, P. (Polina), Lahti, J. (Jari), Tuovinen, S. (Soile), Lipsanen, J. (Jari), Villa, P. M. (Pia M.), Laivuori, H. (Hannele), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Pesonen, A. (Anu‑Katriina), Räikkönen, K. (Katri), Toffol, E. (Elena), Rantalainen, V. (Ville), Lahti‑Pulkkinen, M. (Marius), Girchenko, P. (Polina), Lahti, J. (Jari), Tuovinen, S. (Soile), Lipsanen, J. (Jari), Villa, P. M. (Pia M.), Laivuori, H. (Hannele), Hämäläinen, E. (Esa), Kajantie, E. (Eero), Pesonen, A. (Anu‑Katriina), and Räikkönen, K. (Katri)

Abstract

Whether infant regulatory behavior problems already in the first month of life indicate an increased risk of childhood neurobehavioral problems, and whether maternal depression in the postpartum and early childhood underpins these associations remain unclear. Altogether, 2049–2364 mothers from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) study completed the Neonatal Perception Inventory on regulatory behavior problems at the infant’s age of 15.6 days (SD 3.2, range 1–30), the Infant Behavior Questionnaire-Revised on temperament at 6.5 months (SD 0.9, range 4.2–12.4), and the Ages and Stages Questionnaire-3 on developmental milestones and the Child Behavior Checklist on behavioral problems at 3.5 years (SD 0.7, range 1.9–6.0). Maternal depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale (infancy follow-ups) and Beck Depression Inventory-II (childhood follow-up). Father-rated infant temperament and paternal depressive symptoms were also available (n = 1474). Higher levels of infant regulatory behavior problems predicted higher levels of mother- and father-rated negative affectivity temperament (0.13 SD units per SD unit, 95% confidence interval 0.09–0.17; and 0.09, 0.04–0.14, respectively), lower levels of mother-rated orienting/regulation temperament (− 0.09, − 0.13 to − 0.05) and problem-solving skills (− 0.12, − 0.21 to − 0.04), and higher levels of Externalizing (0.07, 0.03–0.11) and Total behavioral problems (0.07, 0.03–0.11). Regulatory behaviors partially mediated the effect of maternal depressive symptoms. Regulatory behavior problems already during the first month of life predict neurobehavioral outcomes, and partially mediate the effect of maternal depressive symptoms. Our study may inform design of interventions aimed at timely prevention in children at risk.

Published
2019

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