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1. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta‐analysis of European, North American and Australian cohorts

Author: Santos, S, Voerman, E, Amiano, P, Barros, H, Beilin, LJ, Bergström, A, Charles, M‐A, Chatzi, L, Chevrier, C, Chrousos, GP, Corpeleijn, E, Costa, O, Costet, N, Crozier, S, Devereux, G, Doyon, M, Eggesbø, M, Fantini, MP, Farchi, S, Forastiere, F, Georgiu, V, Godfrey, KM, Gori, D, Grote, V, Hanke, W, Hertz‐Picciotto, I, Heude, B, Hivert, M‐F, Hryhorczuk, D, Huang, R‐C, Inskip, H, Karvonen, AM, Kenny, LC, Koletzko, B, Küpers, LK, Lagström, H, Lehmann, I, Magnus, P, Majewska, R, Mäkelä, J, Manios, Y, McAuliffe, FM, McDonald, SW, Mehegan, J, Melén, E, Mommers, M, Morgen, CS, Moschonis, G, Murray, D, Chaoimh, C Ní, Nohr, EA, Andersen, A‐M Nybo, Oken, E, Oostvogels, AJJM, Pac, A, Papadopoulou, E, Pekkanen, J, Pizzi, C, Polanska, K, Porta, D, Richiardi, L, Rifas‐Shiman, SL, Roeleveld, N, Ronfani, L, Santos, AC, Standl, M, Stigum, H, Stoltenberg, C, Thiering, E, Thijs, C, Torrent, M, Tough, SC, Trnovec, T, Turner, S, Gelder, MMHJ, Rossem, L, Berg, A, Vrijheid, M, Vrijkotte, TGM, West, J, Wijga, AH, Wright, J, Zvinchuk, O, Sørensen, TIA, Lawlor, DA, Gaillard, R, and Jaddoe, VWV
Subjects: Obesity, Contraception/Reproduction, Diabetes, Preterm, Low Birth Weight and Health of the Newborn, Infant Mortality, Cardiovascular, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Prevention, Nutrition, Pediatric, Aetiology, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, 2.1 Biological and endogenous factors, Prevention of disease and conditions, and promotion of well-being, Metabolic and endocrine, Reproductive health and childbirth, Good Health and Well Being, Adult, Australia, Birth Weight, Body Mass Index, Cohort Studies, Europe, Female, Gestational Age, Gestational Weight Gain, Humans, Infant, Newborn, North America, Odds Ratio, Overweight, Pregnancy, Pregnancy Complications, Risk Factors, Birthweight, body mass index, pregnancy complications, preterm birth, weight gain, Medical and Health Sciences, Obstetrics & Reproductive Medicine
Abstract: ObjectiveTo assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta-analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265 270 births.MethodsInformation on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain.ConclusionsMaternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity.Tweetable abstractPromoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.
Published: 2019

2. Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood

Author: Elhakeem, A, Taylor, AE, Inskip, HM, Huang, J, Tafflet, M, Vinther, JL, Asta, F, Erkamp, JS, Gagliardi, L, Guerlich, K, Halliday, J, Harskamp-van Ginkel, MW, He, J-R, Jaddoe, VWV, Lewis, S, Maher, GM, Manios, Y, Mansell, T, McCarthy, FP, McDonald, SW, Medda, E, Nisticò, L, de Moira, AP, Popovic, M, Reiss, IKM, Rodrigues, C, Salika, T, Smith, A, Stazi, MA, Walker, C, Wu, M, Åsvold, BO, Barros, H, Brescianini, S, Burgner, D, Chan, JKY, Charles, M-A, Eriksson, JG, Gaillard, R, Grote, V, Håberg, SE, Heude, B, Koletzko, B, Morton, S, Moschonis, G, Murray, D, O'Mahony, D, Porta, D, Qiu, X, Richiardi, L, Rusconi, F, Saffery, R, Tough, SC, Vrijkotte, TGM, Nelson, SM, Nybo Andersen, A-M, Magnus, MC, Lawlor, DA, and Assisted Reproductive Technology and Future Health (ART-Health) Cohort Collaboration
Subjects: Adult, Male, 42 Health sciences, Adolescent, Reproductive Techniques, Assisted, Infant, 32 Biomedical and clinical sciences, Embryo Transfer, Cohort Studies, Pregnancy, Semen, Child, Preschool, Humans, Female, Obesity, Child, Adiposity
Abstract: IMPORTANCE: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. OBJECTIVE: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. EXPOSURES: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). MAIN OUTCOMES AND MEASURES: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. RESULTS: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). CONCLUSIONS AND RELEVANCE: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.
Published: 2022

3. Epigenome-wide contributions to individual differences in childhood phenotypes: a GREML approach

Author: Alexander Neumann, Esther Walton, Janine F. Felix, Pingault J, Henning Tiemeier, Charlotte A.M. Cecil, Jaddoe Vwv, Child and Adolescent Psychiatry / Psychology, Pediatrics, and Epidemiology
Subjects: Birth weight, Population, Individuality, Context (language use), Biology, Epigenesis, Genetic, Epigenome, SDG 3 - Good Health and Well-being, Genetics, Birth Weight, Humans, education, Molecular Biology, Genetics (clinical), education.field_of_study, Gestational age, Methylation, DNA Methylation, Explained variation, Phenotype, DNA methylation, Generation R, CpG Islands, Human medicine, Developmental Biology, Genome-Wide Association Study
Abstract: BackgroundDNA methylation is an epigenetic mechanism involved in human development. Numerous epigenome-wide association studies (EWAS) have investigated the associations of DNA methylation at single CpG sites with childhood outcomes. However, the overall contribution of DNA methylation across the genome (R2Methylation) towards childhood phenotypes is unknown. An estimate ofR2Methylationwould provide context regarding the importance of DNA methylation explaining variance in health outcomes. We therefore estimated the variance explained by epigenome-wide cord blood methylation (R2Methylation) for five childhood phenotypes: gestational age, birth weight, and body mass index (BMI), IQ and ADHD symptoms at school age. We adapted a genome-based restricted maximum likelihood (GREML) approach with cross-validation (CV) to DNA methylation data and applied it in two population-based birth cohorts: ALSPAC (n = 775) and GenerationR(n = 1382).ResultsUsing information from > 470,000 autosomal probes we estimated that DNA methylation at birth explains 32% (SDCV = 0.06) of gestational age variance and 5% (SDCV = 0.02) of birth weight variance. TheR2Methylationestimates for BMI, IQ and ADHD symptoms at school age estimates were near 0% across almost all cross-validation iterations.ConclusionsThe results suggest that cord blood methylation explains a moderate degree of variance in gestational age and birth weight, in line with the success of previous EWAS in identifying numerous CpG sites associated with these phenotypes. In contrast, we could not obtain a reliable estimate for school-age BMI, IQ and ADHD symptoms. This may reflect a null bias due to insufficient sample size to detect variance explained in more weakly associated phenotypes, although the trueR2Methylationfor these phenotypes is likely below that of gestational age and birth weight when using DNA methylation at birth.
Published: 2022

4. Incidence rates and symptomatology of community infections with SARS-CoV-2 in children and parents: The CoKids longitudinal household study

Author: de Hoog, MLA, primary, Sluiter-Post, JGC, additional, Westerhof, I, additional, Fourie, E, additional, Heuvelman, VD, additional, Boom, TT, additional, Euser, SM, additional, Badoux, P, additional, Reusken, C, additional, Bont, LJ, additional, Sanders, L, additional, Jaddoe, VWV, additional, Herpers, BL, additional, Eggink, D, additional, Wildenbeest, JG, additional, Duijts, L, additional, van Houten, MA, additional, and Bruijning-Verhagen, PCJL, additional
Published: 2021
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5. Spectacle wear and refractive errors in Dutch children

Author: Iyer, V, primary, Enthoven, CA, additional, van Dommelen, P, additional, Samkar, A van, additional, Groenewoud, JH, additional, Reijneveld, SA, additional, Jaddoe, VWV, additional, and Klaver, CCW, additional
Published: 2021
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6. Epigenome-wide change and variation in DNA methylation from birth to late adolescence

Author: Lotte C Houtepen, Tom R. Gaunt, Henning Tiemeier, Andrew J Simpkin, Cecil Cam, Janine F. Felix, Jolien Rijlaarsdam, Alexander Neumann, van IJzendoorn Mh, Jaddoe Vwv., Rosa H. Mulder, Caroline L Relton, Bastiaan T. Heijmans, Esther Walton, Matthew Suderman, and Marian J. Bakermans-Kranenburg
Subjects: 0303 health sciences, dNaM, Disease, Epigenome, Biology, Genome, 03 medical and health sciences, 0302 clinical medicine, CpG site, Evolutionary biology, DNA methylation, human activities, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract: DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5,019 blood samples collected at multiple time-points from birth to late adolescence from 2,348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for nonlinear change and inter-individual variation in nonlinear trajectories was somewhat less common (11% and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. By contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often nonlinear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu.ac.uk.
Published: 2020
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7. Association Between Portable Music Player Use and Hearing Loss Among Children of School Age in the Netherlands

Author: André Goedegebure, le Clercq Cmp, Hein Raat, Jaddoe Vwv, Baatenburg de Jong Rj, van der Schroeff Mp, Erasmus MC other, Otorhinolaryngology and Head and Neck Surgery, Epidemiology, Pediatrics, and Public Health
Subjects: Male, medicine.medical_specialty, Cross-sectional study, Hearing loss, Population, Audiology, 03 medical and health sciences, 0302 clinical medicine, Audiometry, Risk Factors, 030225 pediatrics, Prevalence, otorhinolaryngologic diseases, medicine, Humans, Prospective Studies, Child, Hearing Loss, High-Frequency, 030223 otorhinolaryngology, education, Netherlands, education.field_of_study, medicine.diagnostic_test, business.industry, Audiogram, Tympanometry, Cross-Sectional Studies, Acoustic Impedance Tests, Hearing Loss, Noise-Induced, Socioeconomic Factors, Otorhinolaryngology, Cohort, Female, Surgery, medicine.symptom, business, Music, Cohort study
Abstract: Importance Portable music player use may have harmful effects on hearing. The magnitude and effect of frequent music exposure, especially at younger ages, on hearing are unclear. Objectives To examine the prevalence of noise-induced hearing loss in a 9- to 11-year-old population and associations with portable music player use and sociodemographic factors. Design, Setting, and Participants A cross-sectional study within an ongoing, prospective, birth cohort study within Rotterdam, the Netherlands was conducted. Between ages 9 and 11 years, 5355 children underwent their first audiometric evaluation. Children were excluded if they had missing or failed tympanometry results. The study was conducted from April 16, 2012, to October 25, 2015. Exposures Portable music player (PMP) use and sociodemographic factors assessed via parental questionnaires. Main Outcomes and Measures Hearing acuity measured by pure-tone audiometry at 0.5 to 8 kHz. Possible noise-induced hearing loss was contingent on a high-frequency notch and/or high-frequency hearing loss in the audiogram, or reported hearing-related symptoms. Results The final sample included 3116 participants who were a mean (interquartile range) age of 9.7 (9.6-9.9) years and equally distributed between boys (1550 [49.7%]) and girls (1566 [50.3%]). Of these, 1244 (39.9%) reported no PMP use, 577 (18.5%) reported use 1 or 2 days per week, 254 (8.2%) reported use 3 or more days per week, and for 1041 (33.4%), PMP use was not reported. Audiometric notches and high-frequency hearing loss were present in 443 (14.2%) of all children; 140 (4.5%) fulfilled the criteria of a notch, 238 (7.6%) of high-frequency hearing loss, and 65 (2.1%) of both. Of the cohort, 52 (1.7%) showed bilateral impairment. Hearing-related symptoms were reported for 232 (11.3%) of the respondents, and 831 (40.0%) of the respondents used portable music players. Portable music player use was associated with high-frequency hearing loss (odds ratio [OR], 2.88; 95% CI, 1.36-6.980 for 1 or 2 days per week and OR, 2.74; 95% CI, 1.22-6.96 for ≥3 days per week), but listening time and duration were not. There was no association of music exposure with high-frequency notches. Conclusions and Relevance In this study, 14.2% of school-aged children showed audiometric notches or high-frequency hearing loss. This hearing impairment is already present prior to exposure to known noise hazards, such as club and concert attendance, and may have lifelong consequences. Repeated measurements are needed to confirm the association of portable music player use with hearing impairment in children.
Published: 2018

8. A periconceptional energy-rich dietary pattern is associated with early fetal growth: the Generation R study

Author: Bouwland-Both, MI, Steegers-Theunissen, RPM, Vujkovic, M, Lesaffre, EMEH, Mook-Kanamori, DO, Hofman, A, Lindemans, J, Russcher, H, Jaddoe, VWV, and Steegers, EAP
Published: 2013
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9. Homocysteine and folate concentrations in early pregnancy and the risk of adverse pregnancy outcomes: the Generation R Study

Author: Bergen, NE, Jaddoe, VWV, Timmermans, S, Hofman, A, Lindemans, J, Russcher, H, Raat, H, Steegers-Theunissen, RPM, and Steegers, EAP
Published: 2012
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10. Maternal smoking during pregnancy, fetal arterial resistance adaptations and cardiovascular function in childhood

Author: Geelhoed, JJM, el Marroun, H, Verburg, BO, van Osch-Gevers, L, Hofman, A, Huizink, AC, Moll, HA, Verhulst, FC, Helbing, WA, Steegers, EAP, and Jaddoe, VWV
Published: 2011
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11. Comparison of pregnancy outcomes in women with repaired versus unrepaired atrial septal defect

Author: Yap, S-C, Drenthen, W, Meijboom, FJ, Moons, P, Mulder, BJM, Vliegen, HW, van Dijk, APJ, Jaddoe, VWV, Steegers, EAP, Roos-Hesselink, JW, and Pieper, PG
Published: 2009
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12. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author: Couto Alves, A, De Silva, NMG, Karhunen, V, Sovio, U, Das, S, Taal, HR, Warrington, NM, Lewin, AM, Kaakinen, M, Cousminer, DL, Thiering, E, Timpson, NJ, Bond, TA, Lowry, E, Brown, CD, Estivill, X, Lindi, V, Bradfield, JP, Geller, F, Speed, D, Coin, LJM, Loh, M, Barton, SJ, Beilin, LJ, Bisgaard, H, Bønnelykke, K, Alili, R, Hatoum, IJ, Schramm, K, Cartwright, R, Charles, M, Salerno, V, Clément, K, Claringbould, AAJ, BIOS Consortium, van Duijn, CM, Moltchanova, E, Eriksson, JG, Elks, C, Feenstra, B, Flexeder, C, Franks, S, Frayling, TM, Freathy, RM, Elliott, P, Widén, E, Hakonarson, H, Hattersley, AT, Rodriguez, A, Banterle, M, Heinrich, J, Heude, B, Holloway, JW, Hofman, A, Hyppönen, E, Inskip, H, Kaplan, LM, Hedman, AK, Läärä, E, Prokisch, H, Grallert, H, Lakka, TA, Lawlor, DA, Melbye, M, Ahluwalia, TS, Marinelli, M, Millwood, IY, Palmer, LJ, Pennell, CE, Perry, JR, Ring, SM, Savolainen, MJ, Rivadeneira, F, Standl, M, Sunyer, J, Tiesler, CMT, Uitterlinden, AG, Schierding, W, O’Sullivan, JM, Prokopenko, I, Herzig, K, Smith, GD, O'Reilly, P, Felix, JF, Buxton, JL, Blakemore, AIF, Ong, KK, Jaddoe, VWV, Grant, SFA, Sebert, S, McCarthy, MI, Järvelin, M., and Early Growth Genetics (EGG) Consortium
Abstract: Copyright © 2019 The Authors. Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
Published: 2019

13. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

Author: Haworth, S, Shapland, CY, Hayward, C, Prins, BP, Felix, JF, Medina-Gomez, C, Rivadeneira, F, Wang, C, Ahluwalia, TS, Vrijheid, M, Guxens, M, Sunyer, J, Tachmazidou, I, Walter, K, Iotchkova, V, Jackson, A, Cleal, L, Huffmann, J, Min, JL, Sass, L, Timmers, PRHJ, Smith, G, Fisher, SE, Wilson, JF, Cole, TJ, Fernandez-Orth, D, Bønnelykke, K, Bisgaard, H, Pennell, CE, Jaddoe, VWV, Dedoussis, G, Timpson, N, Zeggini, E, Vitart, V, St Pourcain, B, consortium, UK10K, and Bhattacharya, S
Abstract: Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.
Published: 2019

14. Author Correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author: Waage, J, Standl, M, Curtin, JA, Jessen, LE, Thorsen, J, Tian, C, Schoettler, N, 23andMe Research Team, AAGC collaborators, Flores, C, Abdellaoui, A, Ahluwalia, TS, Alves, AC, Amaral, AFS, Antó, JM, Arnold, A, Barreto-Luis, A, Baurecht, H, van Beijsterveldt, CEM, Bleecker, ER, Bonàs-Guarch, S, Boomsma, DI, Brix, S, Bunyavanich, S, Burchard, EG, Chen, Z, Curjuric, I, Custovic, A, den Dekker, HT, Dharmage, SC, Dmitrieva, J, Duijts, L, Ege, MJ, Gauderman, WJ, Georges, M, Gieger, C, Gilliland, F, Granell, R, Gui, H, Hansen, T, Heinrich, J, Henderson, J, Hernandez-Pacheco, N, Holt, P, Imboden, M, Jaddoe, VWV, Jarvelin, M-R, Jarvis, DL, Jensen, KK, Jónsdóttir, I, Kabesch, M, Kaprio, J, Kumar, A, Lee, Y-A, Levin, AM, Li, X, Lorenzo-Diaz, F, Melén, E, Mercader, JM, Meyers, DA, Myers, R, Nicolae, DL, Nohr, EA, Palviainen, T, Paternoster, L, Pennell, CE, Pershagen, G, Pino-Yanes, M, Probst-Hensch, NM, Rüschendorf, F, Simpson, A, Stefansson, K, Sunyer, J, Sveinbjornsson, G, Thiering, E, Thompson, PJ, Torrent, M, Torrents, D, Tung, JY, Wang, CA, Weidinger, S, Weiss, S, Willemsen, G, Williams, LK, Ober, C, Hinds, DA, Ferreira, MA, Bisgaard, H, Strachan, DP, and Bønnelykke, K
Subjects: ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION, ComputingMethodologies_COMPUTERGRAPHICS
Abstract: In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.
Published: 2018

15. Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Author: Waage, J, Standl, M, Curtin, JA, Jessen, L, Thorsen, J, Tian, C, Schoettler, N, The 23andMe Research Team, AAGC Collaborators, Flores, C, Abdellaoui, A, Ahluwalia, TS, Alves, A, Amaral, AFS, Antó, JM, Arnold, A, Barreto-Luis, A, Baurecht, H, van Beijsterveldt, CEM, Bleecker, ER, Bonàs-Guarch, S, Boomsma, D, Brix, S, Bunyavanich, S, Burchard, E, Chen, Z, Curjuric, I, Custovic, A, den Dekker, HT, Dharmage, SC, Dmitrieva, J, Duijts, L, Ege, MJ, Gauderman, WJ, Georges, M, Gieger, C, Gilliland, F, Granell, R, Gui, H, Hansen, T, Heinrich, J, Henderson, J, Hernandez-Pacheco, N, Holt, P, Imboden, M, Jaddoe, VWV, Jarvelin, M-R, Jarvis, DL, Jensen, KK, Jónsdóttir, I, Kabesch, M, Kaprio, J, Kumar, A, Lee, Y-A, Levin, AM, Li, X, Lorenzo-Diaz, F, Melén, E, Mercader, JM, Meyers, DA, Myers, R, Nicolae, DL, Nohr, EA, Palviainen, T, Paternoster, L, Pennell, C, Pershagen, G, Pino-Yanes, M, Probst-Hensch, NM, Rüschendorf, F, Simpson, A, Stefansson, K, Sunyer, J, Sveinbjornsson, G, Thiering, E, Thompson, PJ, Torrent, M, Torrents, D, Tung, JY, Wang, CA, Weidinger, S, Weiss, S, Willemsen, G, Williams, LK, Ober, C, Hinds, DA, Ferreira, MA, Bisgaard, H, Strachan, DP, and Bønnelykke, K
Abstract: Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.
Published: 2018

16. A genome-wide association study for corneal astigmatism: The CREAM Consortium

Author: Shah, Rupal, Li, Q, Zhao, W, Tedja, MS, Tideman, WL, Khawaja, A, Fan, Q, Yazar, S, Williams, KM, Verhoeven, VJM, Xie, J, Wang, YX, Hess, M, Nickels, S, Lackner, KJ, Pärssinen, O, Wedenoja, J, Biino, G, Concas, MP, Uitterlinden, A, Rivadeneira, F, Jaddoe, VWV, Hysi, PG, Sim, X, Tan, N, Tham, Y, Sensaki, S, Hofman, A, Vingerling, JR, Jonas, JB, Mitchell, P, Hammond, CJ, Höhn, R, Baird, PN, Wong, TY, Cheng, C, Teo, YY, Mackey, DA, Williams, C, Saw, S, Klaver, CCW, Guggenheim, Jeremy, Bailey-Wilson, JE, and The CREAM Consortium
Abstract: Purpose: To identify genes and genetic markers associated with corneal astigmatism.\ud Methods: A meta-analysis was performed of genome-wide association studies (GWAS) of corneal astigmatism undertaken for 14 European ancestry (N = 22,250) and 8 Asian ancestry (N = 9,120) cohorts by the CREAM Consortium. Cases were defined as having >0.75 D of corneal astigmatism. For the meta-analysed results of European ancestry cohorts, subsequent gene-based and gene-set analyses were performed using VEGAS2 and MAGMA software. Additionally, estimates of SNP-based heritability for corneal and refractive astigmatism and spherical equivalent were calculated for Europeans using LD score regression.\ud Results: Meta-analysis of all cohorts identified a genome-wide significant locus near the gene PDGFRA (platelet derived growth factor receptor alpha): top SNP: rs7673984, odds ratio = 1.12 (95% CI: 1.08-1.16), P = 5.55 x 10-9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified 3 novel candidate genes for corneal astigmatism in Europeans: CLDN7 (claudin-7), ACP2 (acid phosphatase 2, lysosomal) and TNFAIP8L3 (TNF alpha induced protein 8 like 3).\ud Conclusions: In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified 3 novel candidate genes CLDN7, ACP2 and TNFAIP8L3 that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors to the development of astigmatism.
Published: 2018

17. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author: Felix, JF, Joubert, BR, Baccarelli, AA, Sharp, GC, Almqvist, C, Annesi-Maesano, I, Arshad, H, Baïz, N, Bakermans-Kranenburg, MJ, Bakulski, KM, Binder, EB, Bouchard, L, Breton, CV, Brunekreef, B, Brunst, KJ, Burchard, EG, Bustamante, M, Chatzi, L, Munthe-Kaas, M, Corpeleijn, E, Czamara, D, Dabelea, D, Smith, G, De Boever, P, Duijts, L, Dwyer, T, Eng, C, Eskenazi, B, Everson, TM, Falahi, F, Fallin, MD, Farchi, S, Fernandez, MF, Gao, L, Gaunt, TR, Ghantous, A, Gillman, MW, Gonseth, S, Grote, V, Gruzieva, O, Håberg, SE, Herceg, Z, Hivert, M-F, Holland, N, Holloway, JW, Hoyo, C, Hu, D, Huang, R-C, Huen, K, Järvelin, M-R, Jima, DD, Just, AC, Karagas, MR, Karlsson, R, Karmaus, W, Kechris, KJ, Kere, J, Kogevinas, M, Koletzko, B, Koppelman, GH, Küpers, LK, Ladd-Acosta, C, Lahti, J, Lambrechts, N, Langie, SAS, Lie, RT, Liu, AH, Magnus, MC, Magnus, P, Maguire, RL, Marsit, CJ, McArdle, W, Melén, E, Melton, P, Murphy, SK, Nawrot, TS, Nisticò, L, Nohr, EA, Nordlund, B, Nystad, W, Oh, SS, Oken, E, Page, CM, Perron, P, Pershagen, G, Pizzi, C, Plusquin, M, Raikkonen, K, Reese, SE, Reischl, E, Richiardi, L, Ring, S, Roy, RP, Rzehak, P, Schoeters, G, Schwartz, DA, Sebert, S, Snieder, H, Sørensen, TIA, Starling, AP, Sunyer, J, Taylor, JA, Tiemeier, H, Ullemar, V, Vafeiadi, M, Van Ijzendoorn, MH, Vonk, JM, Vriens, A, Vrijheid, M, Wang, P, Wiemels, JL, Wilcox, AJ, Wright, RJ, Xu, C-J, Xu, Z, Yang, IV, Yousefi, P, Zhang, H, Zhang, W, Zhao, S, Agha, G, Relton, CL, Jaddoe, VWV, London, SJ, Epidemiology, Erasmus MC other, Pediatrics, Child and Adolescent Psychiatry / Psychology, Psychiatry, Research Methods and Techniques, dIRAS RA-2, One Health Chemisch, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Department of Psychology and Logopedics, Helsinki Collegium for Advanced Studies, Medicum, University of Helsinki, and Developmental Psychology Research Group
Subjects: DNA Methylation/physiology, Epidemiology, Maternal Health, education, Embaràs, DISEASE, Environmental Pollution/analysis, Epigenesis, Genetic, Cohort Studies, Prenatal Exposure Delayed Effects/epidemiology, Folic Acid, Pregnancy, Journal Article, Humans, MATERNAL SMOKING, CORD BLOOD, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Cohort Profiles, METAANALYSIS, PRENATAL EXPOSURE, Maternal Exposure/adverse effects, EPIGENOME-WIDE ASSOCIATION, 0104 Statistics, Child Health, Infant, Newborn, DNA METHYLATION DATA, DNA Methylation, Epigenètica, BIRTH-WEIGHT, 3142 Public health care science, environmental and occupational health, Folic Acid/blood, 1117 Public Health And Health Services, Maternal Exposure, Prenatal Exposure Delayed Effects, MENDELIAN RANDOMIZATION, Epigenetics, Female, Human medicine, Environmental Pollution
Abstract: UK Medical Research Council; Wellcome Trust [102215/2/13/2, WT088806, 084762MA]; UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]; UK Medical Research Council Integrative Epidemiology Unit; University of Bristol [MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8]; United States National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK10324]; Swedish Research Council; Swedish Heart-Lung Foundation; Freemason Child House Foundation in Stockholm; MeDALL (Mechanisms of the Development of ALLergy), within the European Union [261357]; Stockholm County Council (ALF); Swedish Foundation for Strategic Research (SSF) [RBc08-0027]; Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet; Swedish Research Council Formas; Swedish Environment Protection Agency; Center for Integrative Research on Childhood Leukemia and the Environment [P01ES018172]; NIH [P50ES018172, R01ES09137, 5P30CA082103, P01 ES009605, R01 ES021369, R01ES023067, K01ES017801, R01ES022216, P30ES007048, R01ES014447, P01ES009581, R826708-01, RD831861-01, P50ES026086, R01DK068001, R01 DK100340, R01 DK076648, R01ES022934, R01HL111108, R01NR013945, R37 HD034568, UL1 TR001082, P30 DK56350]; EPA [RD83451101, RD83615901, RD 82670901, RD 83451301, 83615801-0]; UCSF Comprehensive Cancer Center Support grant [P30 CA82103]; Swiss Science National Foundation [P2LAP3_158674]; Sutter-Stottner Foundation; Commission of the European Community, specific RTD Programme 'Quality of Life and Management of Living Resources' within the 5th Framework Programme [QLRT-2001-00389, QLK1-CT-2002-30582]; 6th Framework Programme [007036]; European Union's Seventh Framework Programme (FP7), project EarlyNutrition [289346]; European Research Council Advanced grant ERC-AdG [322605 META-GROWTH]; Autism Speaks grant [260377]; Funds for Research in Respiratory Health; French Ministry of Research: IFR program; INSERM Nutrition Research Program; French Ministry of Health: Perinatality Program; French National Institute for Population Health Surveillance (INVS); Paris-Sud University; French National Institute for Health Education (INPES); Nestle; Mutuelle Generale de l'Education Nationale (MGEN); French-speaking association for the study of diabetes and metabolism (Alfediam) [2012/51290-6]; EU; European Research Council [ERC-2012-StG.310898, 268479-BREATHE]; Flemish Scientific Research Council (FWO) [N1516112 / G.0.873.11N.10]; European Community's Seventh Framework Programme FP7 project EXPOsOMICS [308610]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA grant [628858]; Bijzonder Onderzoeksfonds (BOF) Hasselt University; Ministry of the Flemish Community (Department of Economics, Science and Innovation); Ministry of the Flemish Community (Department of Environment, Nature and Energy); CEFIC LRI award by the Research Foundation-Flanders (FWO); CEFIC LRI award by the Research Foundation-Flanders (FWO) [12L5216N]; Flemish Institute for Technological Research (VITO) [12L5216N]; Bill AMP; Melinda Gates Foundation Grand Challenges Exploration grant [OPP119403]; Sandler Family Foundation; American Asthma Foundation; National Institutes of Health; National Heart, Lung and Blood Institute [HL117004]; National Institute of Environmental Health Sciences [ES24844]; National Institute on Minority Health and Health Disparities [MD006902, MD009523]; National Institute of General Medical Sciences [GM007546]; Tobacco-Related Disease Research Program [24RT-0025]; Hutchison Whampoa Ltd, Hong Kong; University of Groningen; Well Baby Clinic Foundation Icare; Noordlease; Youth Health Care Drenthe; Biobanking and Biomolecular Research Infrastructure Netherlands [CP2011-19]; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; European Union's Horizon research and innovation programme [733206, 633595]; National Institute of Child and Human Development [R01HD068437]; Netherlands Organization for Health Research and Development [VIDI 016.136.361]; Consolidator grant from the European Research Council [ERC-2014-CoG-648916]; Netherlands' Organization for Scientific Research (NWO VICI); European Research Council ERC; Netherlands' Organization for Scientific Research (NWO Spinoza Award); Gravitation program of the Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO) [024.001.003]; Lung Foundation Netherlands [3.2.12.089]; Fonds de Recherche du Quebec en Sante (FRQ-S) [20697]; Canadian Institute of Health Reseach (CIHR) [MOP 115071]; Diabete Quebec grant; Canadian Diabetes Association operating grant [OG-3-08-2622]; American Diabetes Association Pathways Accelerator Early Investigator Award [1-15-ACE-26]; MRC Integrative Epidemiology Unit - Medical Research Council [MC_UU_12013/1-9]; National Institute of Environmental Health Sciences, National Institutes of Health [K99ES025817]; Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041]; Spanish Ministry of Health [FIS-PI04/1436, FIS-PI08/1151]; Spanish Ministry of Health (FEDER funds) [FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615]; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Fundacio La Marato de TV3 [090430]; EU Commission [261357-MeDALL]; National Institute of Allergy and Infectious Diseases [N01-AI90052]; National Institutes of Health USA [R01 HL082925, R01 HL132321]; Asthma UK [364]; NIAID/NIH [R01AI091905, R01AI121226]; National Institute of Health [R01AI121226, R01 AI091905, R01HL132321]; NIH/NIEHS [N01-ES75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES-49019, Z01 ES044005, ES049033, ES049032]; Norwegian Research Council/BIOBANK [221097]; Oslo University Hospital; Unger-Vetlesens foundation; Norwegian American Womens Club; INCA/Plan Cancer-EVA-INSERM, France; International Childhood Cancer Cohort Consortium (I4C); INCA/Plan Cancer-EVA-INSERM (France); IARC Postdoctoral Fellowship; EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND); NIEHS [R21ES014947, R01ES016772]; NIDDK [R01DK085173]; National Institute of Environmental Health Science [P30 ES025128]; University of Oulu grant [65354]; Oulu University Hospital [2/97, 8/97]; Ministry of Health and Social Affairs [23/251/97, 160/97, 190/97]; National Institute for Health and Welfare, Helsinki [54121]; Regional Institute of Occupational Health, Oulu, Finland [50621, 54231]; EU [QLG1-CT-2000-01643, E51560]; NorFA grant [731, 20056, 30167]; Academy of Finland; NIH-NIEHS [P01 ES022832]; US EPA [RD83544201]; NIH-NIGMS [P20GM104416]; NCI [R25CA134286]; Netherlands Organization for Scientific Research and Development; Netherlands Asthma Fund; Netherlands Ministry of Spatial Planning, Housing, and the Environment; Netherlands Ministry of Health, Welfare, and Sport; MeDALL; European Union under the Health Cooperation Work Program of the 7th Framework program [261357]; Italian National Centre for Disease Prevention and Control (CCM grant); Italian Ministry of Health (art 12); Italian Ministry of Health (12bis Dl.gs.vo) [502/92]; EraNet; EVO; University of Helsinki Research Funds; Signe and Ane Gyllenberg foundation; Emil Aaltonen Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; University of Helsinki; University of Western Australia (UWA); Curtin University; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women's and Infant's Research Foundation (KEMH); Edith Cowan University; National Health and Medical Research Council [1059711]; National Health and Medical Research Council (NHMRC) fellowship [1053384]; Australian National Health and Medical Research Council; United States National Institute of Health; Greek Ministry of Health (programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece); Greek Ministry of Health ('Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health); European Union (EU) [EU FP6-2003-Food-3-NewGeneris, EU FP7 ENV.2007.1.2.2.2, 211250 ESCAPE, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7 ENV.2008.1.2.1.6, 226285 ENRIECO]; National Institutes of Health [NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, NIH-NIEHS R01ES025145]; Centers for Disease Control and Prevention [U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498]; Autism Speaks [7659]; Swedish Research Council through the Swedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF projects); Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Asthma and Allergy Association's Research Foundation; Stiftelsen Frimurare Barnahuset Stockholm; Norwegian Ministry of Health and Care Services; Ministry of the Flemish Community (Flemish Agency for Care and Health); University of Bristol; Ministry of Education and Research; European Union (EU) (EU FP7-HEALTH-single stage CHICOS); European Union (EU) (EU-FP7-HEALTH) [308333 HELIX]; European Union (EU) (EU FP6. STREP HiWATE); UK Medical Research Council; Wellcome Trust [102215/2/13/2, WT088806, 084762MA]; UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]; UK Medical Research Council Integrative Epidemiology Unit; University of Bristol [MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8]; United States National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK10324]; Swedish Research Council; Swedish Heart-Lung Foundation; Freemason Child House Foundation in Stockholm; MeDALL (Mechanisms of the Development of ALLergy), within the European Union [261357]; Stockholm County Council (ALF); Swedish Foundation for Strategic Research (SSF) [RBc08-0027]; Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet; Swedish Research Council Formas; Swedish Environment Protection Agency; Center for Integrative Research on Childhood Leukemia and the Environment [P01ES018172]; NIH [P50ES018172, R01ES09137, 5P30CA082103, P01 ES009605, R01 ES021369, R01ES023067, K01ES017801, R01ES022216, P30ES007048, R01ES014447, P01ES009581, R826708-01, RD831861-01, P50ES026086, R01DK068001, R01 DK100340, R01 DK076648, R01ES022934, R01HL111108, R01NR013945, R37 HD034568, UL1 TR001082, P30 DK56350]; EPA [RD83451101, RD83615901, RD 82670901, RD 83451301, 83615801-0]; UCSF Comprehensive Cancer Center Support grant [P30 CA82103]; Swiss Science National Foundation [P2LAP3_158674]; Sutter-Stottner Foundation; Commission of the European Community, specific RTD Programme 'Quality of Life and Management of Living Resources' within the 5th Framework Programme [QLRT-2001-00389, QLK1-CT-2002-30582]; 6th Framework Programme [007036]; European Union's Seventh Framework Programme (FP7), project EarlyNutrition [289346]; European Research Council Advanced grant ERC-AdG [322605 META-GROWTH]; Autism Speaks grant [260377]; Funds for Research in Respiratory Health; French Ministry of Research: IFR program; INSERM Nutrition Research Program; French Ministry of Health: Perinatality Program; French National Institute for Population Health Surveillance (INVS); Paris-Sud University; French National Institute for Health Education (INPES); Nestle; Mutuelle Generale de l'Education Nationale (MGEN); French-speaking association for the study of diabetes and metabolism (Alfediam) [2012/51290-6]; EU; European Research Council [ERC-2012-StG.310898, 268479-BREATHE]; Flemish Scientific Research Council (FWO) [N1516112 / G.0.873.11N.10]; European Community's Seventh Framework Programme FP7 project EXPOsOMICS [308610]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA grant [628858]; Bijzonder Onderzoeksfonds (BOF) Hasselt University; Ministry of the Flemish Community (Department of Economics, Science and Innovation); Ministry of the Flemish Community (Department of Environment, Nature and Energy); CEFIC LRI award by the Research Foundation-Flanders (FWO); CEFIC LRI award by the Research Foundation-Flanders (FWO) [12L5216N]; Flemish Institute for Technological Research (VITO) [12L5216N]; Bill AMP; Melinda Gates Foundation Grand Challenges Exploration grant [OPP119403]; Sandler Family Foundation; American Asthma Foundation; National Institutes of Health; National Heart, Lung and Blood Institute [HL117004]; National Institute of Environmental Health Sciences [ES24844]; National Institute on Minority Health and Health Disparities [MD006902, MD009523]; National Institute of General Medical Sciences [GM007546]; Tobacco-Related Disease Research Program [24RT-0025]; Hutchison Whampoa Ltd, Hong Kong; University of Groningen; Well Baby Clinic Foundation Icare; Noordlease; Youth Health Care Drenthe; Biobanking and Biomolecular Research Infrastructure Netherlands [CP2011-19]; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; European Union's Horizon research and innovation programme [733206, 633595]; National Institute of Child and Human Development [R01HD068437]; Netherlands Organization for Health Research and Development [VIDI 016.136.361]; Consolidator grant from the European Research Council [ERC-2014-CoG-648916]; Netherlands' Organization for Scientific Research (NWO VICI); European Research Council ERC; Netherlands' Organization for Scientific Research (NWO Spinoza Award); Gravitation program of the Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO) [024.001.003]; Lung Foundation Netherlands [3.2.12.089]; Fonds de Recherche du Quebec en Sante (FRQ-S) [20697]; Canadian Institute of Health Reseach (CIHR) [MOP 115071]; Diabete Quebec grant; Canadian Diabetes Association operating grant [OG-3-08-2622]; American Diabetes Association Pathways Accelerator Early Investigator Award [1-15-ACE-26]; MRC Integrative Epidemiology Unit - Medical Research Council [MC_UU_12013/1-9]; National Institute of Environmental Health Sciences, National Institutes of Health [K99ES025817]; Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041]; Spanish Ministry of Health [FIS-PI04/1436, FIS-PI08/1151]; Spanish Ministry of Health (FEDER funds) [FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615]; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Fundacio La Marato de TV3 [090430]; EU Commission [261357-MeDALL]; National Institute of Allergy and Infectious Diseases [N01-AI90052]; National Institutes of Health USA [R01 HL082925, R01 HL132321]; Asthma UK [364]; NIAID/NIH [R01AI091905, R01AI121226]; National Institute of Health [R01AI121226, R01 AI091905, R01HL132321]; NIH/NIEHS [N01-ES75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES-49019, Z01 ES044005, ES049033, ES049032]; Norwegian Research Council/BIOBANK [221097]; Oslo University Hospital; Unger-Vetlesens foundation; Norwegian American Womens Club; INCA/Plan Cancer-EVA-INSERM, France; International Childhood Cancer Cohort Consortium (I4C); INCA/Plan Cancer-EVA-INSERM (France); IARC Postdoctoral Fellowship; EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND); NIEHS [R21ES014947, R01ES016772]; NIDDK [R01DK085173]; National Institute of Environmental Health Science [P30 ES025128]; University of Oulu grant [65354]; Oulu University Hospital [2/97, 8/97]; Ministry of Health and Social Affairs [23/251/97, 160/97, 190/97]; National Institute for Health and Welfare, Helsinki [54121]; Regional Institute of Occupational Health, Oulu, Finland [50621, 54231]; EU [QLG1-CT-2000-01643, E51560]; NorFA grant [731, 20056, 30167]; Academy of Finland; NIH-NIEHS [P01 ES022832]; US EPA [RD83544201]; NIH-NIGMS [P20GM104416]; NCI [R25CA134286]; Netherlands Organization for Scientific Research and Development; Netherlands Asthma Fund; Netherlands Ministry of Spatial Planning, Housing, and the Environment; Netherlands Ministry of Health, Welfare, and Sport; MeDALL; European Union under the Health Cooperation Work Program of the 7th Framework program [261357]; Italian National Centre for Disease Prevention and Control (CCM grant); Italian Ministry of Health (art 12); Italian Ministry of Health (12bis Dl.gs.vo) [502/92]; EraNet; EVO; University of Helsinki Research Funds; Signe and Ane Gyllenberg foundation; Emil Aaltonen Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; University of Helsinki; University of Western Australia (UWA); Curtin University; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women's and Infant's Research Foundation (KEMH); Edith Cowan University; National Health and Medical Research Council [1059711]; National Health and Medical Research Council (NHMRC) fellowship [1053384]; Australian National Health and Medical Research Council; United States National Institute of Health; Greek Ministry of Health (programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece); Greek Ministry of Health ('Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health); European Union (EU) [EU FP6-2003-Food-3-NewGeneris, EU FP7 ENV.2007.1.2.2.2, 211250 ESCAPE, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7 ENV.2008.1.2.1.6, 226285 ENRIECO]; National Institutes of Health [NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, NIH-NIEHS R01ES025145]; Centers for Disease Control and Prevention [U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498]; Autism Speaks [7659]; Swedish Research Council through the Swedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF projects); Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Asthma and Allergy Association's Research Foundation; Stiftelsen Frimurare Barnahuset Stockholm; Norwegian Ministry of Health and Care Services; Ministry of the Flemish Community (Flemish Agency for Care and Health); University of Bristol; Ministry of Education and Research; European Union (EU) (EU FP7-HEALTH-single stage CHICOS); European Union (EU) (EU-FP7-HEALTH) [308333 HELIX]; European Union (EU) (EU FP6. STREP HiWATE); [R01ES017646]; [R01ES01900]; [R01ES16443]; [USA / NIHH 2000 G DF682]; [50945]; [R01 HL095606]; [R01 HL1143396]
Published: 2018

18. Genetic Basis for Gestation Length

Author: Pennell, CE, Warrington, NM, Mook-Kanamori, D, Lye, SJ, Newnham, JP, Palmer, LJ, Jaddoe, VWV, Freathy, RM, Jacobssen, B, Holloway, J, McCarthy, MI, Frayling, TM, Consortium, PGP, and Consortium, EGG
Published: 2016

19. The influence of maternal obesity on the long-term health of the offspring

Author: Godfrey, KM, Reynolds, RM, Prescott, SL, Nyirenda, M, Jaddoe, VWV, Eriksson, JG, Broekman, BFP, and Psychiatry
Abstract: In addition to immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of off spring health during childhood and later adult life. Observational studies provide evidence for eff ects of maternal obesity on her off spring's risks of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Maternal obesity could also lead to poorer cognitive performance and increased risk of neurodevelopmental disorders, including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious-disease-related outcomes. Insights from experimental studies support causal eff ects of maternal obesity on off spring outcomes, which are mediated at least partly through changes in epigenetic processes, such as alterations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the off spring of obese women who lose weight before pregnancy have a reduced risk of obesity, few controlled intervention studies have been done in which maternal obesity is reversed and the consequences for off spring have been examined. Because the long-term eff ects of maternal obesity could have profound public health implications, there is an urgent need for studies on causality, underlying mechanisms, and eff ective interventions to reverse the epidemic of obesity in women of childbearing age and to mitigate consequences for off spring.
Published: 2016

20. Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Author: Paternoster, L, Standl, M, Waage, J, Baurecht, H, Hotze, M, Strachan, DP, Curtin, JA, Bonnelykke, K, Tian, C, Takahashi, A, Esparza-Gordillo, J, Alves, AC, Thyssen, JP, den Dekker, HT, Ferreira, MA, Altmaier, E, Sleiman, PMA, Xiao, FL, Gonzalez, JR, Marenholz, I, Kalb, B, Pino-Yanes, M, Xu, C-J, Carstensen, L, Groen-Blokhuis, MM, Venturini, C, Pennell, CE, Barton, SJ, Levin, AM, Curjuric, I, Bustamante, M, Kreiner-Moller, E, Lockett, GA, Bacelis, J, Bunyavanich, S, Myers, RA, Matanovic, A, Kumar, A, Tung, JY, Hirota, T, Kubo, M, McArdle, WL, Henderson, AJ, Kemp, JP, Zheng, J, Smith, GD, Rueschendorf, F, Bauerfeind, A, Lee-Kirsch, MA, Arnold, A, Homuth, G, Schmidt, CO, Mangold, E, Cichon, S, Keil, T, Rodriguez, E, Peters, A, Franke, A, Lieb, W, Novak, N, Foelster-Holst, R, Horikoshi, M, Pekkanen, J, Sebert, S, Husemoen, LL, Grarup, N, De Jongste, JC, Rivadeneira, F, Hofman, A, Jaddoe, VWV, Pasmans, SGMA, Elbert, NJ, Uitterlinden, AG, Marks, GB, Thompson, PJ, Matheson, MC, Robertson, CF, Ried, JS, Li, J, Zuo, XB, Zheng, XD, Yin, XY, Sun, LD, McAleer, MA, O'Regan, GM, Fahy, CMR, Campbell, LE, Macek, M, Kurek, M, Hu, D, Eng, C, Postma, DS, Feenstra, B, Geller, F, Hottenga, JJ, Middeldorp, CM, Hysi, P, Bataille, V, Spector, T, Tiesler, CMT, Thiering, E, Pahukasahasram, B, Yang, JJ, Imboden, M, Huntsman, S, Vilor-Tejedor, N, Relton, CL, Myhre, R, Nystad, W, Custovic, A, Weiss, ST, Meyers, DA, Soederhaell, C, Melen, E, Ober, C, Raby, BA, Simpson, A, Jacobsson, B, Holloway, JW, Bisgaard, H, Sunyer, J, Probst-Hensch, NM, Williams, LK, Godfrey, KM, Wang, CA, Boomsma, DI, Melbye, M, Koppelman, GH, Jarvis, D, McLean, WHI, Irvine, AD, Zhang, XJ, Hakonarson, H, Gieger-, C, Burchard, EG, Martin, NG, Duijts, L, Linneberg, A, Jarvelin, M-R, Noethen, MM, Lau, S, Huebner, N, Lee, Y-A, Tamari, M, Hinds, DA, Glass, D, Brown, SJ, Heinrich, J, Evans, DM, Weidinger, S, AAGC, AAGC, and Epidemio, EGL
Abstract: Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis.
Published: 2015

21. Influence of fetal blood flow redistribution on fetal and childhood growth and fat distribution: the Generation R Study

Author: Kooijman, MN, primary, Gaillard, R, additional, Reiss, IKM, additional, Hofman, A, additional, Steegers, EAP, additional, and Jaddoe, VWV, additional
Published: 2016
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22. Associations of maternal prepregnancy body mass index and gestational weight gain with cardio-metabolic risk factors in adolescent offspring: a prospective cohort study

Author: Gaillard, R, primary, Welten, M, additional, Oddy, WH, additional, Beilin, LJ, additional, Mori, TA, additional, Jaddoe, VWV, additional, and Huang, R-C, additional
Published: 2015
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23. Fetal sex dependency of maternal vascular adaptation to pregnancy: a prospective population‐based cohort study

Author: Broere‐Brown, ZA, primary, Schalekamp‐Timmermans, S, additional, Hofman, A, additional, Jaddoe, VWV, additional, and Steegers, EAP, additional
Published: 2015
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24. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight

Author: James F. Wilson, Leena Peltonen, Ida Surakka, D S Postma, Albert Hofman, Jouke-Jan Hottenga, Johan G. Eriksson, Ulla Sovio, Dennis O. Mook-Kanamori, Joachim Heinrich, Beverley M. Shields, Nicholas J. Timpson, George Dedoussis, A. H. Wijga, Paul F. O'Reilly, Chen C-M., Hong Xiang Zhang, Jarvelin M-R., Marika Kaakinen, Nabila Bouatia-Naji, Chris Power, Paul Elliott, A Pouta, Jonathan P. Bradfield, Andrew T. Hattersley, Marjan Kerkhof, Inga Prokopenko, Fernando Rivadeneira, Steegers Eap., Linda S. Adair, Jaddoe Vwv., Craig E. Pennell, Philippe Froguel, Panagiotis Deloukas, Dorret I. Boomsma, Anja Taanila, Hartikainen A-L., Julie A. Marsh, Holly Jmp., Nicole M. Warrington, Mirna Kirin, Bridget A. Knight, Rachel M. Freathy, Gonneke Willemsen, E. Widen, Timothy M. Frayling, André G. Uitterlinden, Gerard H. Koppelman, Diana L. Cousminer, Judith B. Borja, de Geus Ejc., Adaikalavan Ramasamy, Amanda J. Bennett, Jianhua Zhao, Matthew W. Gillman, Mark I. McCarthy, Cecilia M. Lindgren, Karen L. Mohlke, Coin Ljm., Joel N. Hirschhorn, Nigel W. Rayner, Y S Aulchenko, Carla M. T. Tiesler, Christopher J. Groves, Susan M. Ring, Lyle J. Palmer, G. Davey Smith, C.M. van Duijn, Beate Glaser, Wendy L. McArdle, J. Laitinen, Reedik Mägi, Hakon Hakonarson, David M. Evans, David P. Strachan, Diane J. Berry, Grant Sfa., Neelam Hassanali, Leslie A. Lange, Pimphen Charoen, Helen N. Lyon, Stavroula Kanoni, Elina Hyppönen, Faculteit Medische Wetenschappen/UMCG, Groningen Research Institute for Asthma and COPD (GRIAC), Freathy, Rachel M, Mook-Kanamori, Dennis O, Sovio, Ulla, Prokopenko, Inga, Hypponen, Elina, McCarthy, Mark I, Biological Psychology, EMGO+ - Mental Health, Erasmus MC other, Epidemiology, Gastroenterology & Hepatology, Internal Medicine, Obstetrics & Gynecology, Public Health, and Medical Research Council (MRC)
Subjects: Netherlands Twin Register (NTR), Male, Genome-wide association study, Type 2 diabetes, Cohort Studies, 0302 clinical medicine, Pregnancy, Ethnicity, Birth Weight, GESTATIONAL-AGE, Genetics & Heredity, 0303 health sciences, Gestational age, 11 Medical And Health Sciences, 3. Good health, Isoenzymes, HEAD CIRCUMFERENCE, Wellcome Trust Case Control Consortium, Female, Life Sciences & Biomedicine, Adenylyl Cyclases, Adenylate Cyclase, EXPRESSION, medicine.medical_specialty, Genotype, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Birth weight, Ethnic Groups, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, ISOFORMS, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Early Growth Genetics (EGG) Consortium, Internal medicine, Diabetes mellitus, Cyclins, Genetics, medicine, Humans, Genetic Predisposition to Disease, COHORT, GENOME-WIDE ASSOCIATION, Alleles, METAANALYSIS, 030304 developmental biology, Fetus, Science & Technology, Models, Genetic, ADENYLYL-CYCLASE, 06 Biological Sciences, medicine.disease, GENE, Endocrinology, Glucose, Diabetes Mellitus, Type 2, Meta-Analyses of Glucose and Insulin-related traits Consortium, TYPE-2 DIABETES RISK, Developmental Biology
Abstract: To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 × 10 35) and rs9883204 in ADCY5 (P = 7 × 10 15) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113g (95% CI 89-137g) lighter at birth than the 24% with zero or one alleles (P trend = 7 × 10 30). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy. © 2010 Nature America, Inc. All rights reserved.
Published: 2010

25. O-214 Growth Trajectories And Bone Mineral Density In Children With Subclinical Celiac Disease: The Generation R Study

Author: Jansen, MAE, primary, Kiefte-de Jong, JC, additional, Gaillard, R, additional, Escher, JC, additional, Hofman, A, additional, Jaddoe, VWV, additional, Hooijkaas, H, additional, and Moll, HA, additional
Published: 2014
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26. O-172 Infant Feeding And Anti-tissue Transglutaminase Antibody Levels In Children With Subclinical Celiac Disease: The Generation R Study

Author: Tromp, IIM, primary, Jansen, MAE, additional, Kiefte-de Jong, JC, additional, Jaddoe, VWV, additional, Hofman, A, additional, Escher, JC, additional, Hooijkaas, H, additional, and Moll, HA, additional
Published: 2014
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27. Maternal haemoglobin levels and cardio-metabolic risk factors in childhood: the Generation R Study

Author: Welten, M, primary, Gaillard, R, additional, Hofman, A, additional, de Jonge, LL, additional, and Jaddoe, VWV, additional
Published: 2014
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28. Fetal sex dependency of maternal vascular adaptation to pregnancy: a prospective population-based cohort study.

Author: Broere‐Brown, ZA, Schalekamp‐Timmermans, S, Hofman, A, Jaddoe, VWV, Steegers, EAP, Broere-Brown, Z A, and Schalekamp-Timmermans, S
Subjects: PREGNANCY complications, VASCULAR resistance, FETAL growth retardation, PREECLAMPSIA, DURATION of pregnancy, PREMATURE labor, THERAPEUTICS, ARTERIAL physiology, DOPPLER ultrasonography, PHYSIOLOGICAL adaptation, BIRTH weight, BLOOD pressure, FETAL ultrasonic imaging, LONGITUDINAL method, MATERNAL age, PHYSICS, PLACENTA, SEX distribution, CASE-control method
Abstract: Objective: To investigate fetal sex dependency of maternal vascular adaptation to pregnancy as assessed by uteroplacental vascular resistance and maternal blood pressure.Design: Prospective population-based cohort study.Setting: Rotterdam, the Netherlands.Population: In total, 8224 liveborn singleton pregnancies were included.Methods: Maternal vascular adaptation was assessed in all trimesters of pregnancy. Pregnancies were stratified into being either complicated by the placental syndrome (i.e. pre-eclampsia, fetal growth restriction or preterm birth, n = 1229) or uncomplicated (n = 6995).Main Outcome Measures: First trimester: blood pressures. Second trimester: blood pressures, pulsatility index of the uterine artery (PI-UtA). Third trimester: blood pressures, PI-UtA, presence of notching in the uterine artery.Results: In women carrying a male fetus PI-UtA was higher than in women with a female fetus in the total group (second trimester P < 0.001, third trimester P = 0.005). Effect estimates differed between women with or without the placental syndrome. In the total group, women with a male fetus more often showed notching in the Doppler resistance pattern (odds ratio 1.42, 95% confidence interval 1.17-1.72). Different blood pressure patterns were observed between pregnant women with a male fetus and pregnant women with a female fetus and between complicated pregnancies and uncomplicated pregnancies.Conclusion: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy with differential effects in uncomplicated pregnancies and in pregnancies complicated by the placental syndrome.Tweetable Abstract: Fetal sex is significantly associated with maternal vascular adaptation to pregnancy. [ABSTRACT FROM AUTHOR]
Published: 2016
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29. Associations of maternal prepregnancy body mass index and gestational weight gain with cardio-metabolic risk factors in adolescent offspring: a prospective cohort study.

Author: Gaillard, R, Welten, M, Oddy, WH, Beilin, LJ, Mori, TA, Jaddoe, VWV, Huang, R‐C, Oddy, W H, Beilin, L J, Mori, T A, Jaddoe, V W V, and Huang, R-C
Subjects: PREGNANCY complications, WEIGHT gain, COHORT analysis, BODY mass index, METABOLISM, CARDIOVASCULAR disease prevention, PREVENTION of obesity, OBESITY complications, BLOOD pressure, CARDIOVASCULAR diseases, LONGITUDINAL method, OBESITY, RESEARCH funding, DISEASE prevalence, METABOLIC syndrome, WAIST-hip ratio, WAIST circumference, PRENATAL exposure delayed effects, PREVENTION
Abstract: Objective: To assess the associations of maternal prepregnancy body mass index (BMI) and rates of early-pregnancy, mid-pregnancy and total gestational weight gain with adolescent body fat distribution and cardio-metabolic outcomes.Design: Population-based prospective cohort study.Setting: Western Australia.Population: Thousand three hundred and ninety-two mothers and their children.Methods: Maternal prepregnancy weight was assessed by questionnaire. Maternal weights at a mean of 16.5 ± 2.2 SD and 34.1 ± 1.5 SD weeks of gestation were obtained from medical records. Offspring adiposity and cardio-metabolic outcomes were assessed at a median age 17.0 years [95% confidence interval (CI) range: 16.7, 17.7].Main Outcome Measures: Adolescent BMI, waist circumference (WC), waist-to-hip ratio (WHR), blood pressure, total and HDL-cholesterol, triglycerides, insulin, glucose and HOMA-IR.Results: Higher prepregnancy BMI was associated with higher adolescent BMI, WC, WHR, systolic blood pressure, insulin, glucose and HOMA-IR levels (P-values <0.05). Adjustment for adolescent current BMI attenuated the associations of prepregnancy BMI with adolescent cardio-metabolic outcomes. Higher weight gain in early-pregnancy, but not mid-pregnancy, was associated with higher adolescent BMI, WC and WHR (P-values <0.05), but not with other cardio-metabolic risk factors. Total gestational weight gain was associated with adolescent BMI and WC (P-values <0.05). Higher prepregnancy BMI and early-pregnancy weight gain were associated with increased risks of the high-metabolic risk cluster in adolescents (OR 1.57, 95% CI 1.33, 1.85 and OR 1.23, 95% CI 1.03, 1.47 per SD increase in prepregnancy BMI and early-pregnancy weight gain, respectively).Conclusions: Higher maternal prepregnancy BMI and early-pregnancy weight gain rate are associated with an adverse adolescent cardio-metabolic profile. These associations are largely mediated by adolescent BMI. [ABSTRACT FROM AUTHOR]
Published: 2016
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30. A periconceptional energy-rich dietary pattern is associated with early fetal growth: the Generation R study

Author: Bouwland-Both, MI, primary, Steegers-Theunissen, RPM, additional, Vujkovic, M, additional, Lesaffre, EMEH, additional, Mook-Kanamori, DO, additional, Hofman, A, additional, Lindemans, J, additional, Russcher, H, additional, Jaddoe, VWV, additional, and Steegers, EAP, additional
Published: 2012
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31. Perinatal outcomes and gestational weight gain in women with eating disorders: a population‐based cohort study

Author: Micali, N, primary, De Stavola, B, additional, dos‐Santos‐Silva, I, additional, Steenweg‐de Graaff, J, additional, Jansen, PW, additional, Jaddoe, VWV, additional, Hofman, A, additional, Verhulst, FC, additional, Steegers, EAP, additional, and Tiemeier, H, additional
Published: 2012
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32. Explaining differences in birth outcomes in relation to maternal age: the Generation R Study

Author: Bakker, R, primary, Steegers, EAP, additional, Biharie, AA, additional, Mackenbach, JP, additional, Hofman, A, additional, and Jaddoe, VWV, additional
Published: 2011
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33. Dose-response relationship between alcohol consumption before and during pregnancy and the risks of low birthweight, preterm birth and small for gestational age (SGA)-a systematic review and meta-analyses

Author: Patra, J, primary, Bakker, R, additional, Irving, H, additional, Jaddoe, VWV, additional, Malini, S, additional, and Rehm, J, additional
Published: 2011
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34. Perinatal complications increase the risk of postpartum depression. The Generation R Study

Author: Blom, EA, primary, Jansen, PW, additional, Verhulst, FC, additional, Hofman, A, additional, Raat, H, additional, Jaddoe, VWV, additional, Coolman, M, additional, Steegers, EAP, additional, and Tiemeier, H, additional
Published: 2010
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35. Maternal anthropometrics are associated with fetal size in different periods of pregnancy and at birth. The Generation R Study

Author: Ay, L, primary, Kruithof, CJ, additional, Bakker, R, additional, Steegers, EAP, additional, Witteman, JCM, additional, Moll, HA, additional, Hofman, A, additional, Mackenbach, JP, additional, Hokken‐Koelega, ACS, additional, and Jaddoe, VWV, additional
Published: 2009
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36. Explaining differences in birthweight between ethnic populations. The Generation R Study

Author: Troe, EJWM, primary, Raat, H, additional, Jaddoe, VWV, additional, Hofman, A, additional, Looman, CWN, additional, Moll, HA, additional, Steegers, EAP, additional, Verhulst, FC, additional, Witteman, JCM, additional, and Mackenbach, JP, additional
Published: 2007
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37. Maternal haemoglobin levels and cardio-metabolic risk factors in childhood: the Generation R Study.

Author: Welten, M, Gaillard, R, Hofman, A, Jonge, LL, and Jaddoe, VWV
Subjects: HEMOGLOBINS, NUTRITION in pregnancy, MATERNAL health, PREGNANCY complication risk factors, COHORT analysis
Abstract: Objective To assess whether variations in maternal haemoglobin levels during pregnancy are associated with cardio-metabolic risk factors in school age children. Design Population-based prospective cohort study. Setting Rotterdam, The Netherlands, 2002-2012. Population Mothers and children ( n = 5002) participating in the Generation R Study. Methods We obtained maternal haemoglobin levels during early pregnancy (median gestational age 14.6 weeks [95% range 10.3, 25.3]) from venous blood samples. Maternal anaemia and elevated haemoglobin levels were based on World Health Organization criteria. We measured childhood cardio-metabolic risk factors at age 6 years. Main outcome measures Cardio-metabolic risk factors included body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic and diastolic blood pressure, left ventricular mass, and blood levels of cholesterol, insulin and C-peptide. Results Maternal haemoglobin levels were not associated with childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, systolic blood pressure, cholesterol or insulin levels. Compared with children with normal maternal haemoglobin levels, children from anaemic mothers had slightly higher diastolic blood pressures (difference 0.70 mmHg, 95% CI 0.12, 1.29) and lower C-peptide levels (difference factor 0.93, 95% CI 0.88, 0.98), and children of mothers with elevated haemoglobin levels had lower left ventricular masses (difference −1.08 g, 95% CI −1.88, −0.29). These associations attenuated after adjustment for multiple testing and were not consistent within linear models. Conclusion These results do not strongly support the hypothesis that variations in maternal haemoglobin levels during pregnancy influence cardio-metabolic risk factors in childhood. [ABSTRACT FROM AUTHOR]
Published: 2015
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38. Maternal psychological distress and fetal growth trajectories: the Generation R Study.

Author: Henrichs J, Schenk JJ, Roza SJ, van den Berg MP, Schmidt HG, Steegers EAP, Hofman A, Jaddoe VWV, Verhulst FC, and Tiemeier H
Abstract: BACKGROUND: Previous research suggests, though not consistently, that maternal psychological distress during pregnancy leads to adverse birth outcomes. We investigated whether maternal psychological distress affects fetal growth during the period of mid-pregnancy until birth. METHOD: Pregnant women (n=6313) reported levels of psychological distress using the Brief Symptom Inventory (anxious and depressive symptoms) and the Family Assessment Device (family stress) at 20.6 weeks pregnancy and had fetal ultrasound measurements in mid- and late pregnancy. Estimated fetal weight was calculated using head circumference, abdominal circumference and femur length. RESULTS: In mid-pregnancy, maternal distress was not linked to fetal size. In late pregnancy, however, anxious symptoms were related to fetal size after controlling for potential confounders. Anxious symptoms were also associated with a 37.73 g [95% confidence interval (CI) -69.22 to -6.25, p=0.019] lower birth weight. When we related maternal distress to fetal growth curves using multilevel models, more consistent results emerged. Maternal symptoms of anxiety or depression were associated with impaired fetal weight gain and impaired fetal head and abdominal growth. For example, depressive symptoms reduced fetal weight gain by 2.86 g (95% CI -4.48 to -1.23, p<0.001) per week. CONCLUSIONS: The study suggests that, starting in mid-pregnancy, fetal growth can be affected by different aspects of maternal distress. In particular, children of prenatally anxious mothers seem to display impaired fetal growth patterns during pregnancy. Future work should address the biological mechanisms underlying the association of maternal distress with fetal development and focus on the effects of reducing psychological distress in pregnancy. [ABSTRACT FROM AUTHOR]
Published: 2010
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39. Maternal folic acid supplement use in early pregnancy and child behavioural problems: the Generation R Study.

Author: Roza SJ, van Batenburg-Eddes T, Steegers EAP, Jaddoe VWV, Mackenbach JP, Hofman A, Verhulst FC, and Tiemeier H
Published: 2010
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40. Maternal pre- and postnatal anxiety and infant temperament. The generation R study.

Author: Henrichs J, Schenk JJ, Schmidt HG, Velders FP, Hofman A, Jaddoe VWV, Verhulst FC, and Tiemeier H
Abstract: The aim of this study was to investigate whether maternal anxiety that is temporary or chronic during the pre- and postnatal period predicts infant temperament. Mothers of 2997 infants in a population-based birth cohort reported levels of pregnancy-specific anxiety (Pregnancy Outcome Questionnaire) and general anxiety symptoms (Brief Symptom Inventory) prenatal and at 6 months postnatal. Temperament characteristics were assessed by maternal report using the Infant Behavior Questionnaire-Revised when the infants were 6 months of age. Maternal pregnancy-specific and general anxiety during the pre- and postnatal period were all independently associated with perceived infant temperamental difficulties. Chronically high maternal anxiety predicted the highest perceived infant activity level and negative affectivity. These findings show that different forms of maternal anxiety during both the pre- and postnatal period are independently related to perceived temperamental problems in infancy. They also emphasize the significance of chronic maternal anxiety for infant mental health. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
Published: 2009
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41. Cerebral ventricular volume and temperamental difficulties in infancy. The Generation R Study.

Author: Roza SJ, Govaert PP, Lequin MH, Jaddoe VWV, Moll HA, Steegers EAP, Hofman A, Verhulst FC, and Tiemeier H
Abstract: BACKGROUND: Numerous studies have provided evidence for subtle deviations in brain morphology in children with psychiatric disorders, but much less is known about the onset and developmental trajectory of these deviations early in life. We sought to determine whether variances in cerebral ventricular size in fetuses and newborns are associated with temperamental difficulties in infants. METHODS: Within a population-based cohort study, we measured the size of the lateral ventricle of the fetus' brain twice during pregnancy. We used 3-dimensional cranial ultrasound to measure the cerebral ventricular volume of infants at age 6 weeks. We then related the size of the cerebral ventricular system to temperamental dimensions at age 3 months using the Mother and Baby Scales, and at age 6 months using the Infant Behavior Questionnaire for a total of 1028 infants. RESULTS: The size of the lateral ventricle of the fetuses in midpregnancy was not related to temperamental difficulties in infants; however, smaller lateral ventricles in late pregnancy were associated with higher activity levels at the age of 6 months. Infants with smaller ventricular volumes at age 6 weeks experienced higher activity levels, more anger or irritability and poorer orienting later in infancy. Children with the lowest ventricular volumes scored on average 0.15 (95% confidence interval 0.06-0.23, p = 0.001) points higher (23%) on activity levels than children with the highest ventricular volumes. CONCLUSION: Variations in ventricular size before and shortly after birth are associated with temperamental difficulties. Some of the morphologic differences between children with and without psychiatric disorders may develop very early in life. [ABSTRACT FROM AUTHOR]
Published: 2008

42. Moderate alcohol consumption during pregnancy and the risk of low birth weight and preterm birth. The Generation X Study.

Author: Jaddoe VWV, Bakker R, Hofman A, Mackenbach JP, Moll HA, Steegers EAP, and Witteman JCM
Abstract: PURPOSE: To examine the associations of alcohol consumption in different periods of pregnancy with the risks of low birth weight and preterm birth. METHODS: This study was based on 7141 subjects participating in a population-based prospective cohort study from early pregnancy. Alcohol consumption was assessed in early, mid, and late pregnancy. Birth outcomes were birth weight in grams, low birth weight (<2500 g), small size for gestational age at birth (< -2 standard deviation scores) and preterm birth (gestational age <37 weeks). RESULTS: Overall, alcohol consumption during pregnancy was not associated with adverse birth outcomes. However, dose-response analyses showed tendencies toward adverse effects of average consumption of 1 or more alcoholic drinks per day in early pregnancy on birth weight (difference -129 g [95% confidence interval (CI): -271, 12]), low birth weight (adjusted odds ratio [aOR] 4.81 [95% CI: 1.10, 21.08]), small size for gestational age at birth (aOR 1.45 [95% CI: 0.33, 6.44]) and preterm birth (aOR 2.51 [95% CI: 0.92, 6.81]). Similar effects were found in late pregnancy. CONCLUSION: Average consumption of one or more but not less than one alcoholic drink per day in early or late pregnancy seems to be associated with adverse birth outcomes in the offspring. [ABSTRACT FROM AUTHOR]
Published: 2007
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43. Genome-wide associations for birth weight and correlations with adult disease

Author: Horikoshi, M, Beaumont, RN, Day, FR, Warrington, NM, Kooijman, MN, Fernandez-Tajes, J, Feenstra, B, Van Zuydam, NR, Gaulton, KJ, Grarup, N, Bradfield, JP, Strachan, DP, Li-Gao, R, Ahluwalia, TS, Kreiner, E, Rueedi, R, Lyytikäinen, L-P, Cousminer, DL, Wu, Y, Thiering, E, Wang, CA, Have, CT, Hottenga, J-J, Vilor-Tejedor, N, Joshi, PK, Boh, ETH, Ntalla, I, Pitkänen, N, Mahajan, A, Van Leeuwen, EM, Joro, R, Lagou, V, Nodzenski, M, Diver, LA, Zondervan, KT, Bustamante, M, Marques-Vidal, P, Mercader, JM, Bennett, AJ, Rahmioglu, N, Nyholt, DR, Ma, RCW, Tam, CHT, Tam, WH, CHARGE Consortium Hematology Working Group, Ganesh, SK, Van Rooij, FJA, Jones, SE, Loh, P-R, Ruth, KS, Tuke, MA, Tyrrell, J, Wood, AR, Yaghootkar, H, Scholtens, DM, Paternoster, L, Prokopenko, I, Kovacs, P, Atalay, M, Willems, SM, Panoutsopoulou, K, Wang, X, Carstensen, L, Geller, F, Schraut, KE, Murcia, M, Van Beijsterveldt, CEM, Willemsen, G, Appel, EVR, Fonvig, CE, Trier, C, Tiesler, CMT, Standl, M, Kutalik, Z, Bonàs-Guarch, S, Hougaard, DM, Sánchez, F, Torrents, D, Waage, J, Hollegaard, MV, De Haan, HG, Rosendaal, FR, Medina-Gomez, C, Ring, SM, Hemani, G, McMahon, G, Robertson, NR, Groves, CJ, Langenberg, C, Luan, J, Scott, RA, Zhao, JH, Mentch, FD, MacKenzie, SM, Reynolds, RM, Early Growth Genetics (EGG) Consortium, Lowe, WL, Tönjes, A, Stumvoll, M, Lindi, V, Lakka, TA, Van Duijn, CM, Kiess, W, Körner, A, Sørensen, TIA, Niinikoski, H, Pahkala, K, Raitakari, OT, Zeggini, E, Dedoussis, GV, Teo, Y-Y, Saw, S-M, Melbye, M, Campbell, H, Wilson, JF, Vrijheid, M, De Geus, EJCN, Boomsma, DI, Kadarmideen, HN, Holm, J-C, Hansen, T, Sebert, S, Hattersley, AT, Beilin, LJ, Newnham, JP, Pennell, CE, Heinrich, J, Adair, LS, Borja, JB, Mohlke, KL, Eriksson, JG, Widén, E, Kähönen, M, Viikari, JS, Lehtimäki, T, Vollenweider, P, Bønnelykke, K, Bisgaard, H, Mook-Kanamori, DO, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Pisinger, C, Pedersen, O, Power, C, Hyppönen, E, Wareham, NJ, Hakonarson, H, Davies, E, Walker, BR, Jaddoe, VWV, Järvelin, M-R, Grant, SFA, Vaag, AA, Lawlor, DA, Frayling, TM, Smith, GD, Morris, AP, Ong, KK, Felix, JF, Timpson, NJ, Perry, JRB, Evans, DM, McCarthy, MI, and Freathy, RM
Subjects: quantitative trait, hypertension, intrauterine growth, genome-wide association studies, metabolic disorders, 3. Good health
Abstract: Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$ < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$ = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$ = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$ = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

44. Prolonged and exclusive breastfeeding reduces the risk of infectious diseases in infancy.

Author: Duijts L, Jaddoe VWV, Hofman A, and Moll HA
Abstract: OBJECTIVE: To examine the associations of duration of exclusive breastfeeding with infections in the upper respiratory (URTI), lower respiratory (LRTI), and gastrointestinal tracts (GI) in infancy. METHODS: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward in the Netherlands. Rates of breastfeeding during the first 6 months (never; partial for <4 months, not thereafter; partial for 4-6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended infections in the URTI, LRTI, and GI until the age of 12 months were assessed by questionnaires and available for 4164 subjects. RESULTS: Compared with never-breastfed infants, those who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of infections in the URTI, LRTI, and GI until the age of 6 months (adjusted odds ratio [aOR]: 0.65 [95% confidence interval (CI): 0.51-0.83]; aOR: 0.50 [CI: 0.32-0.79]; and aOR: 0.41 [CI: 0.26-0.64], respectively) and of LRTI infections between the ages of 7 and 12 months (aOR: 0.46 [CI: 0.31-0.69]). Similar tendencies were observed for infants who were exclusively breastfed for 6 months or longer. Partial breastfeeding, even for 6 months, did not result in significantly lower risks of these infections. CONCLUSIONS: Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants. Our findings support health-policy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries. [ABSTRACT FROM AUTHOR]
Published: 2010
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45. Paternal depressive symptoms during pregnancy are related to excessive infant crying.

Author: van den Berg MP, van der Ende J, Crijnen AAM, Jaddoe VWV, Moll HA, Mackenbach JP, Hofman A, Hengeveld MW, Tiemeier H, and Verhulst FC
Published: 2009
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46. Are starting and continuing breastfeeding related to educational background? The Generation R Study.

Author: van Rossem L, Oenema A, Steegers EAP, Moll HA, Jaddoe VWV, Hofman A, Mackenbach JP, and Raat H
Published: 2009
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47. A catalog of genetic loci associated with kidney function from analyses of a million individuals

Author: Wuttke, Matthias, Li, Yong, Li, Man, Sieber, Karsten B., Feitosa, Mary F., Gorski, Mathias, Tin, Adrienne, Wang, Lihua, Chu, Audrey Y., Hoppmann, Anselm, Kirsten, Holger, Giri, Ayush, Chai, Jin-Fang, Sveinbjornsson, Gardar, Tayo, Bamidele O., Nutile, Teresa, Fuchsberger, Christian, Marten, Jonathan, Cocca, Massimiliano, Ghasemi, Sahar, Xu, Yizhe, Horn, Katrin, Noce, Damia, van der Most, Peter J., Sedaghat, Sanaz, Yu, Zhi, Akiyama, Masato, Afaq, Saima, Ahluwalia, Tarunveer S., Almgren, Peter, Amin, Najaf, Ärnlöv, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boehnke, Michael, Boerwinkle, Eric, Boissel, Mathilde, Bottinger, Erwin P., Boutin, Thibaud S., Brenner, Hermann, Brumat, Marco, Burkhardt, Ralph, Butterworth, Adam S., Campana, Eric, Campbell, Archie, Campbell, Harry, Canouil, Mickaël, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Chee, Miao-Ling, Chee, Miao-Li, Chen, Xu, Cheng, Ching-Yu, Cheng, Yurong, Christensen, Kaare, Cifkova, Renata, Ciullo, Marina, Pina Concas, Maria, Cook, James P., Coresh, Josef, Corre, Tanguy, Sala, Cinzia Felicita, Cusi, Daniele, Danesh, John, Daw, E. Warwick, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Delgado, Graciela, Demirkan, Ayse, Di Angelantonio, Emanuele, Dittrich, Katalin, Divers, Jasmin, Dorajoo, Rajkumar, Eckardt, Kai-Uwe, Ehret, Georg, Elliott, Paul, Endlich, Karlhans, Evans, Michele K., Felix, Janine F., Foo, Valencia Hui Xian, Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Friedlander, Yechiel, Froguel, Philippe, Gansevoort, Ron T., Gao, He, Gasparini, Paolo, Gaziano, J. Michael, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Giulianini, Franco, Gögele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hartman, Catharina A., Hayward, Caroline, Hellwege, Jacklyn N., Heng, Chew-Kiat, Hickst, Andrew A., Hofer, Edith, Huang, Wei, Hutri-Kähönen, Nina, Hwang, Shih-Jen, ikram, M. Arfan, indridason, Olafur S., Ingelsson, Erik, ising, Marcus, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Jonas, Jost B, Joshi, Peter K., Shilpa Josyula, Navya, Jung, Bettina, Kähönen, Mika, Kamatani, Yoichiro, Kammerer, Candace M., Kanai, Masahiro, Kastarinen, Mika, Kerr, Shona M., Khor, Chiea-Chuen, Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kraja, Aldi T., Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kühnel, Brigitte, Kuokkanen, Mikko, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lange, Leslie A., Langefeld, Carl D., Jen-Mai Lee, Jeannette, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Cohort Study, Lifelines, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J. F., Lucae, Susanne, Ann Lukas, Mary, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Christa Meisinger, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K., Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P., Veteran Program, V. A. Million, Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., Nadkarni, Girish N, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, ilja M., Noordam, Raymond, O’Connell, Jeffrey, O’Donoghue, Michelle L., Olafsson, Isleifur, Oldehinkel, Albertine J., Orho-Melander, Marju, Ouwehand, Willem H., Padmanabhan, Sandosh, Palmer, Nicholette D., Palsson, Runolfur, Penninx, Brenda W. J. H., Perls, Thomas, Perola, Markus, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Podgornaia, Anna I., Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Pramstaller, Peter P., Preuss, Michael H., Prins, Bram P., Province, Michael A., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Ridker, Paul M., Rivadeneira, Fernando, Rizzi, Federica, Roberts, David J., Robino, Antonietta, Rossing, Peter, Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Sabanayagam, Charumathi, Salomaa, Veikko, Salvi, Erika, Saum, Kai-Uwe, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Schupf, Nicole, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Smith, Blair H., Soranzo, Nicole, Spracklen, Cassandra N., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Svensson, Per O., Szymczak, Silke, Tai, E-Shyong, Tajuddin, Salman M., Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorleifsson, Gudmar, Toniolo, Daniela, Tönjes, Anke, Tremblay, Johanne, Tzoulaki, Ioanna, Uitterlinden, André G., Vaccargiu, Simona, van Dam, Rob M., van der Harst, Pim, van Duijn, Cornelia M., Velez Edward, Digna R., Verweij, Niek, Vogelezang, suzanne, Völker, üwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Wallentin, Lars, Wang, Ya Xing, Wang, Chaolong, Waterworth, Dawn M., Bin Wei, Wen, White, Harvey, Whitfield, John B., Wild, Sarah H., Wilson, James F., Wojczynski, Mary K., Wong, Charlene, Wong, Tien-Yin, Xu, Liang, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Weihua, Zonderman, Alan B., Rotter, Jerome I., Bochud, Murielle, Psaty, Bruce M., Vitart, Veronique, Wilson, James G., Dehghan, Abbas, Parsa, Afshin, Chasman, Daniel I., Ho, Kevin, Morris, Andrew P., Devuyst, Olivier, Akilesh, Shreeram, Pendergrass, Sarah A., Sim, Xueling, Böger, Carsten A., Okada, Yukinori, Edwards, Todd L., Snieder, Harold, Stefansson, Kari, Hung, Adriana M., Heid, Iris M., Markus Scholz, Teumer, Alexander, Köttgen, Anna, Pattaro, Cristian, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Internal Medicine, Epidemiology, Erasmus MC other, Pediatrics, Psychiatry, APH - Mental Health, APH - Digital Health, Wuttke, M, Li, Y, Li, M, Sieber, Kb, Feitosa, Mf, Gorski, M, Tin, A, Wang, L, Chu, Ay, Hoppmann, A, Kirsten, H, Giri, A, Chai, Jf, Sveinbjornsson, G, Tayo, Bo, Nutile, T, Fuchsberger, C, Marten, J, Cocca, M, Ghasemi, S, Xu, Y, Horn, K, Noce, D, van der Most, Pj, Sedaghat, S, Yu, Z, Akiyama, M, Afaq, S, Ahluwalia, T, Almgren, P, Amin, N, Ärnlöv, J, Bakker, Sjl, Bansal, N, Baptista, D, Bergmann, S, Biggs, Ml, Biino, G, Boehnke, M, Boerwinkle, E, Boissel, M, Bottinger, Ep, Boutin, T, Brenner, H, Brumat, M, Burkhardt, R, Butterworth, A, Campana, Eric, Campbell, A, Campbell, H, Canouil, M, Carroll, Rj, Catamo, E, Chambers, Jc, Chee, Ml, Chen, X, Cheng, Cy, Cheng, Y, Christensen, K, Cifkova, R, Ciullo, M, Concas, Mp, Cook, Jp, Coresh, J, Corre, T, Sala, Cf, Cusi, D, Danesh, J, Daw, Ew, de Borst, Mh, De Grandi, A, de Mutsert, R, de Vries, Apj, Degenhardt, F, Delgado, G, Demirkan, A, Di Angelantonio, E, Dittrich, K, Divers, J, Dorajoo, R, Eckardt, Ku, Ehret, G, Elliott, P, Endlich, K, Evans, Mk, Felix, Jf, Foo, Vhx, Franco, Oh, Franke, A, Freedman, Bi, Freitag-Wolf, S, Friedlander, Y, Froguel, P, Gansevoort, Rt, Gao, H, Gasparini, P, Gaziano, Jm, Giedraitis, V, Gieger, C, Girotto, G, Giulianini, F, Gögele, M, Gordon, Sd, Gudbjartsson, Df, Gudnason, V, Haller, T, Hamet, P, Harris, Tb, Hartman, Ca, Hayward, C, Hellwege, Jn, Heng, Ck, Hicks, Aa, Hofer, E, Huang, W, Hutri-Kähönen, N, Hwang, Sj, Ikram, Ma, Indridason, O, Ingelsson, E, Ising, M, Jaddoe, Vwv, Jakobsdottir, J, Jonas, Jb, Joshi, Pk, Josyula, N, Jung, B, Kähönen, M, Kamatani, Y, Kammerer, Cm, Kanai, M, Kastarinen, M, Kerr, Sm, Khor, Cc, Kiess, W, Kleber, Me, Koenig, W, Kooner, J, Körner, A, Kovacs, P, Kraja, At, Krajcoviechova, A, Kramer, H, Krämer, Bk, Kronenberg, F, Kubo, M, Kühnel, B, Kuokkanen, M, Kuusisto, J, La Bianca, M, Laakso, M, Lange, La, Langefeld, Cd, Lee, Jj, Lehne, B, Lehtimäki, T, Lieb, W, Lifelines Cohort, Study, Lim, Sc, Lind, L, Lindgren, Cm, Liu, J, Loeffler, M, Loos, Rjf, Lucae, S, Lukas, Ma, Lyytikäinen, Lp, Mägi, R, Magnusson, Pke, Mahajan, A, Martin, Ng, Martins, J, März, W, Mascalzoni, D, Matsuda, K, Meisinger, C, Meitinger, T, Melander, O, Metspalu, A, Mikaelsdottir, Ek, Milaneschi, Y, Miliku, K, Mishra, Pp, V. A., Million Veteran Program, Mohlke, Kl, Mononen, N, Montgomery, Gw, Mook-Kanamori, Do, Mychaleckyj, Jc, Nadkarni, Gn, Nalls, Ma, Nauck, M, Nikus, K, Ning, B, Nolte, Im, Noordam, R, O'Connell, J, O'Donoghue, Ml, Olafsson, I, Oldehinkel, Aj, Orho-Melander, M, Ouwehand, Wh, Padmanabhan, S, Palmer, Nd, Palsson, R, Penninx, Bwjh, Perls, T, Perola, M, Pirastu, M, Pirastu, N, Pistis, G, Podgornaia, Ai, Polasek, O, Ponte, B, Porteous, Dj, Poulain, T, Pramstaller, Pp, Preuss, Mh, Prins, Bp, Province, Ma, Rabelink, Tj, Raffield, Lm, Raitakari, Ot, Reilly, Df, Rettig, R, Rheinberger, M, Rice, Km, Ridker, Pm, Rivadeneira, F, Rizzi, F, Roberts, Dj, Robino, A, Rossing, P, Rudan, I, Rueedi, R, Ruggiero, D, Ryan, Ka, Saba, Y, Sabanayagam, C, Salomaa, V, Salvi, E, Saum, Ku, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, Ca, Schupf, N, Shaffer, Cm, Shi, Y, Smith, Av, Smith, Bh, Soranzo, N, Spracklen, Cn, Strauch, K, Stringham, Hm, Stumvoll, M, Svensson, Po, Szymczak, S, Tai, E, Tajuddin, Sm, Tan, Nyq, Taylor, Kd, Teren, A, Tham, Yc, Thiery, J, Thio, Chl, Thomsen, H, Thorleifsson, G, Toniolo, D, Tönjes, A, Tremblay, J, Tzoulaki, I, Uitterlinden, Ag, Vaccargiu, S, van Dam, Rm, van der Harst, P, van Duijn, Cm, Velez Edward, Dr, Verweij, N, Vogelezang, S, Völker, U, Vollenweider, P, Waeber, G, Waldenberger, M, Wallentin, L, Wang, Yx, Wang, C, Waterworth, Dm, Bin Wei, W, White, H, Whitfield, Jb, Wild, Sh, Wilson, Jf, Wojczynski, Mk, Wong, C, Wong, Ty, Xu, L, Yang, Q, Yasuda, M, Yerges-Armstrong, Lm, Zhang, W, Zonderman, Ab, Rotter, Ji, Bochud, M, Psaty, Bm, Vitart, V, Wilson, Jg, Dehghan, A, Parsa, A, Chasman, Di, Ho, K, Morris, Ap, Devuyst, O, Akilesh, S, Pendergrass, Sa, Sim, X, Böger, Ca, Okada, Y, Edwards, Tl, Snieder, H, Stefansson, K, Hung, Am, Heid, Im, Scholz, M, Teumer, A, Köttgen, A, and Pattaro, C.
Subjects: catalog, Inheritance Patterns, Hasso-Plattner-Institut für Digital Engineering GmbH, Genome-wide association study, Disease, Kidney Function Tests, Bioinformatics, DISEASE, 0302 clinical medicine, Uromodulin/urine, kidney function, 11 Medical and Health Sciences, Genetics & Heredity, ddc:616, 0303 health sciences, Kidney, Genome-wide association, HERITABILITY, GENOME-WIDE ASSOCIATION, COMMON VARIANTS, RENAL-FUNCTION, TRANS-EQTLS, METAANALYSIS, TRANSPORTER, CLASSIFICATION, INTEGRATION, Chromosome Mapping, 3. Good health, Phenotype, medicine.anatomical_structure, Medical genetics, Common variants, Renal function, Trans-EQTLS, Metaanalysis, Heritability, Transporter, Life Sciences & Biomedicine, Glomerular Filtration Rate, Metaanalysi, medicine.medical_specialty, Genotype, European Continental Ancestry Group, Quantitative Trait Loci, Common variant, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, White People, V. A. Million Veteran Program, 03 medical and health sciences, Quantitative Trait, Heritable, Lifelines Cohort Study, Uromodulin, Genetics, medicine, Humans, Genetic Predisposition to Disease, Renal Insufficiency, Chronic, Genetic Association Studies, 030304 developmental biology, Genetic association, Science & Technology, urogenital system, association, genetic loci, 06 Biological Sciences, medicine.disease, Renal Insufficiency, Chronic/genetics/physiopathology/urine, Genetic Association Studies/methods, ddc:000, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study, Kidney disease
Abstract: Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Published: 2019

48. Associations of childhood BMI, general and visceral fat mass with metabolite profiles at school-age.

Author: Schipper MC, Blaauwendraad SM, Koletzko B, Oei EHG, Jaddoe VWV, and Gaillard R
Subjects: Humans, Child, Male, Female, Cross-Sectional Studies, Metabolome physiology, Intra-Abdominal Fat metabolism, Body Mass Index, Pediatric Obesity blood
Abstract: Background: Childhood obesity increases metabolic disease risk. Underlying mechanisms remain unknown. We examined associations of body mass index (BMI), total body fat mass, and visceral fat mass with serum metabolites at school-age, and explored whether identified metabolites improved the identification of children at risk of a metabolically unhealthy phenotype., Methods: We performed a cross-sectional analysis among 497 children with a mean age of 9.8 (95% range 9.1, 10.6) years, participating in a population-based cohort study. We measured BMI, total body fat mass using DXA, and visceral fat mass using MRI. Serum concentrations of amino-acids, non-esterified-fatty-acids, phospholipids, and carnitines were determined using LC-MS/MS. Children were categorized as metabolically healthy or metabolically unhealthy, according to BMI, blood pressure, lipids, glucose, and insulin levels., Results: Higher BMI and total body fat mass were associated with altered concentrations of branched-chain amino-acids, essential amino-acids, and free carnitines. Higher BMI was also associated with higher concentrations of aromatic amino-acids and alkyl-lysophosphatidylcholines (FDR-corrected p-values < 0.05). The strongest associations were present for Lyso.PC.a.C14.0 and SM.a.C32.2 (FDR-corrected p-values < 0.01). Higher visceral fat mass was only associated with higher concentrations of 6 individual metabolites, particularly Lyso.PC.a.C14.0, PC.aa.C32.1, and SM.a.C32.2. We selected 15 metabolites that improved the prediction of a metabolically unhealthy phenotype, compared to BMI only (AUC: BMI: 0.59 [95% CI 0.47,0.71], BMI + Metabolites: 0.91 [95% CI 0.85,0.97])., Conclusions: An adverse childhood body fat profile, characterized by higher BMI and total body fat mass, is associated with metabolic alterations, particularly in amino acids, phospholipids, and carnitines. Fewer associations were present for visceral fat mass. We identified a metabolite profile that improved the identification of impaired cardiometabolic health in children, compared to BMI only., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2024
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49. The cardiovascular exercise response in children with overweight or obesity children measured by cardiovascular magnetic resonance imaging.

Author: Bongers-Karmaoui MN, Hirsch A, Budde RPJ, Roest AAW, Jaddoe VWV, and Gaillard R
Abstract: Background: Overweight and obesity are among the main causes of cardiovascular diseases. Exercise testing can aid in the early detection of subtle cardiac dysfunction not present in rest. We hypothesized that the cardiovascular response to exercise is impaired among children with overweight or obesity, characterized by the inability of the cardiovascular system to adapt to exercise by increasing cardiac volumes and blood pressure. We performed a cardiovascular stress test to investigate whether the cardiovascular exercise response is altered in children with overweight and obesity, as compared to children with a normal weight., Subjects: A subgroup of the Generation R population-based prospective cohort study, consisting of 41 children with overweight or obesity and 166 children with a normal weight with a mean age of 16 years, performed an isometric exercise., Methods: Continuous heart rate and blood pressure were measured during rest, exercise and recovery. Cardiovascular magnetic resonance (CMR) measurements were performed during rest and exercise., Results: Higher BMI was associated with a higher resting systolic and diastolic blood pressure (difference: 0.24 SDS (95% CI 0.10, 0.37) and 0.20 SDS (95% CI 0.06, 0.33)) and lower systolic and diastolic blood pressure increases from rest to peak exercise (-0.11 SDS (95% CI -0.20, -0.03) and -0.07 SDS (95% CI -0.07, -0.01)). BMI was also associated with a slower decrease in systolic and diastolic blood pressure during recovery (p values < 0.05). Higher childhood BMI was associated with lower BSA corrected left ventricular mass, end-diastolic volume and stroke volume (p values < 0.05). There were no associations of childhood BMI with the cardiac response to exercise measured by heart rate and CMR measurements., Conclusion: Childhood BMI is, across the full range, associated with a blunted blood pressure response to static exercise but there were no differences in cardiac response to exercise. Our findings suggest that adiposity may especially affect the vascular exercise reaction without affecting cardiac response., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2024
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50. Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children.

Author: Fernandes A, Avraam D, Cadman T, Dadvand P, Guxens M, Binter AC, Pinot de Moira A, Nieuwenhuijsen M, Duijts L, Julvez J, De Castro M, Fossati S, Márquez S, Vrijkotte T, Elhakeem A, McEachan R, Yang T, Pedersen M, Vinther J, Lepeule J, Heude B, Jaddoe VWV, Santos S, Welten M, El Marroun H, Mian A, Andrušaitytė S, Lertxundi A, Ibarluzea J, Ballester F, Esplugues A, Torres Toda M, Harris JR, Lucia Thorbjørnsrud Nader J, Moirano G, Maritano S, Catherine Wilson R, and Vrijheid M
Subjects: Humans, Child, Female, Europe, Pregnancy, Male, Child, Preschool, Neurodevelopmental Disorders epidemiology, Asthma epidemiology
Abstract: Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV 1 (β = 0.06; 95 %CI: 0.03, 0.09 I 2 = 4.03 %, p < 0.001) and FVC (β = 0.07; 95 %CI: 0.04, 0.09 I 2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (β = -0.04; 95 %CI: -0.07, -0.02, I 2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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