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108. Health behaviours prior to pregnancy and fertility outcomes: Triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa)

Author

Robyn E Wootton, Rebecca B Lawn, Maria Magnus, Jorien Treur, Elizabeth Corfield, Pal R Njolstad, Ole A Andreassen, Deborah A Lawlor, Marcus R Munafo, Siri E Haberg, George Davey Smith, Ted Reichborn-Kjennerud, Per Magnus, and Alexandra Havdahl

Abstract

Introduction: Current advice to improve fertility includes reducing alcohol and caffeine consumption, achieving healthy weight-range, and stopping smoking. Advice is informed by observational evidence, which is often biased by confounding. Methods: This study uses data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway. First, we analysed associations between health behaviours prior to pregnancy (alcohol and caffeine consumption, body-mass index (BMI) and smoking) and multiple indicators of fertility (including number of children, time to conception, and miscarriage) (n=83,128 women, 67,555 men), adjusting for birthyear, education and attention deficit and hyperactive-impulsive (ADHD) traits. Second, we used individual-level Mendelian randomisation (MR) to explore possible causal effects of health behaviours on fertility outcomes (n=27,216 women, 26,131 men). Finally, we performed summary-level MR for available outcomes (n=91,462-1,232,091) and conducted multi-variable MR to control for education and ADHD liability. Results: In observational analysis, higher BMI and smoking (and to a lesser extent caffeine) were predominantly associated with reduced fertility outcomes. Unexpectedly, higher alcohol consumption was associated with predominantly improved fertility outcomes. There was little evidence from individual-level MR analyses, except smoking and higher BMI were associated with younger age at first birth in women (mean difference in years, per SD increase in genetic score; smoking: -2.65 (95%CI: -3.57, -1.73); BMI: -0.11 (95%CI: -0.16, -0.08)) and men (smoking: -2.82 (95%CI: -4.07, -1.58); BMI: -0.17 (95%CI: -0.23, -0.11)). These results were replicated in the summary-level MR analysis, however effects attenuated after adjusting for education and ADHD liability. Conclusions: Most observational evidence for associations between health behaviours and fertility was not supported by MR analyses, suggesting possible residual confounding. Evidence from MR analyses supported an effect of smoking and higher BMI on younger age of first birth, but multivariable MR suggested this might be explained by underlying liability to ADHD and low educational attainment.

Published
2022
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110. Long-Range Gene Regulation Links Genomic Type 2 Diabetes and Obesity Risk Regions to HHEX, SOX4, and IRX3

Author

Ragvin, Anja, Moro, Enrico, Fredman, David, Navratilova, Pavla, Drivenes, Øyvind, Engström, Pär G., Alonso, M. Eva, de la Calle Mustienes, Elisa, Skarmeta, José Luis Gómez, Tavares, Maria J., Casares, Fernando, Manzanares, Miguel, van Heyningen, Veronica, Molven, Anders, Njølstad, Pål R., Argenton, Francesco, Lenhard, Boris, Becker, Thomas S., and Levine, Michael S.

Published
2010
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113. Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms

Author

Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)

Abstract

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84–2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%–8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| < 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42–0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Published
2022

114. Capacity constraints as a trigger for high growth

Author

Universitat Rovira i Virgili, Coad A; Domnick C; Flachenecker F; Harasztosi P; Janiri ML; Pal R; Teruel M, Universitat Rovira i Virgili, and Coad A; Domnick C; Flachenecker F; Harasztosi P; Janiri ML; Pal R; Teruel M

Abstract

High-growth enterprises (HGEs) have a large economic impact but are notoriously hard to predict. Previous research has linked high-growth episodes to the configuration of lumpy indivisible resources inside firms, such that high capacity utilisation levels might stimulate future growth. We theorize that firms reaching critically high capacity utilisation levels reach a “trigger point” involving either broad-based investment in further growth or shrinking back to previous levels. We analyze EIBIS survey data (matched to ORBIS) which features a question on time-varying capacity utilisation. Overcapacity is a transitory state. Firms enter into overcapacity after a period of the rapid growth of sales and profits, and the years surrounding overcapacity have higher employment growth rates. Firms operating at overcapacity make incremental investments (e.g. capacity expansion, process improvements and modern machinery) rather than investing in R&D and new product development. We find support for the “fork in the road” hypothesis: for some firms, overcapacity is associated with launching into massive investments and subsequent sales growth, while for other firms, overcapacity is negatively related to both investments and sales growth. Operating above maximum capacity is like a “fork in the road”: while some firms shrink back to stay within existing capacity constraints, others respond by launching into broad-based growth. We develop a theory of firm growth, according to which some firms are better positioned for subsequent growth, depending upon their state of capacity utilisation. Firms with plenty of slack capacity can easily grow within the bounds of existing capacity constraints. Firms that are already operating above maximum capacity cannot grow by drawing on slack

Published
2022

116. Diabetes and Pancreatic Exocrine Dysfunction Due to Mutations in the Carboxyl Ester Lipase Gene-Maturity Onset Diabetes of the Young (CEL-MODY): A PROTEIN MISFOLDING DISEASE

Author

Johansson, Bente B., Torsvik, Janniche, Bjørkhaug, Lise, Vesterhus, Mette, Ragvin, Anja, Tjora, Erling, Fjeld, Karianne, Hoem, Dag, Johansson, Stefan, Ræder, Helge, Lindquist, Susanne, Hernell, Olle, Cnop, Miriam, Saraste, Jaakko, Flatmark, Torgeir, Molven, Anders, and Njølstad, Pål R.

Published
2011
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123. Health behaviours prior to pregnancy and fertility outcomes: Triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa)

Author

Wootton, Robyn E, primary, Lawn, Rebecca B, additional, Magnus, Maria, additional, Treur, Jorien, additional, Corfield, Elizabeth, additional, Njolstad, Pal R, additional, Andreassen, Ole A, additional, Lawlor, Deborah A, additional, Munafo, Marcus R, additional, Haberg, Siri E, additional, Davey Smith, George, additional, Reichborn-Kjennerud, Ted, additional, Magnus, Per, additional, and Havdahl, Alexandra, additional

Published
2022
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125. Premature Adult Death in Individuals Born Preterm: A Sibling Comparison in a Prospective Nationwide Follow-Up Study.

Author

Kari R Risnes, Kristine Pape, Johan H Bjørngaard, Dag Moster, Michael B Bracken, and Pal R Romundstad

Subjects
Medicine, Science
Abstract

Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings.Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses.Compared with a sibling born in week 37-41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population.Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings.

Published
2016
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129. List of contributors

Author

Allen, J., primary, Ash, R.A., additional, Asija, N., additional, Bhatnagar, A., additional, Bhatnagar, N., additional, Bracamonte, L., additional, Carr, D.J., additional, Crawford, C., additional, Cronin, J., additional, Dartois, M., additional, Dixit, D., additional, Gotts, Phil, additional, Helliker, A., additional, Kapoor, G., additional, Kinsler, R., additional, Lewis, E., additional, Loutfy, R., additional, Pal, R., additional, Quéfélec, B., additional, Rajan, S.D., additional, Stabenau, M., additional, Tam, T., additional, Webster, G.A.T., additional, Walsh, S.M., additional, Yilmazcoban, I.K., additional, and Zheng, J.Q., additional

Published
2016
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133. Vaccines for Control of Fertility

Author

Talwar, G. P., Singh, Om, Pal, R., Sad, S., Arunan, K., Chatterjee, N., Kausic, C., Upadhyay, S. N., Sahai, P., Singh, M., Chandrasekhar, S., Gupta, H., Salunke, D., Gergely, János, editor, Benczúr, M., editor, Erdei, Anna, editor, Falus, A., editor, Füst, Gy., editor, Medgyesi, G., editor, Petrányi, Gy., editor, and Rajnavölgyi, Éva, editor

Published
1993
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134. GROWTH DYNAMICS AND COTTON YIELD UNDER VARIABLE THERMAL REGIMES IN SOUTH-WESTERN PUNJAB.

Author

Kaur, Varinderjit, Singh, Som Pal, Pal, R K, Kingra, P K, Sandhu, Sandeep Singh, and Singh, Jatinderpal

Subjects
LEAF area index, SEED yield, COTTONSEED, COTTON, BT cotton, WEATHER
Abstract

A study was carried out during 2020 and 2021 to examine the growth dynamics and cotton yield under various thermal regimes in south western Punjab. The experiment was planned in a factorial randomized complete block design with four sowing dates and two cultivars and replicated thrice. There was a significant decline in growth and yield attributes of tested cultivars with each successive delay in sowing from April 01. Early sown crop recorded higher seed cotton yield (2223-2956 kg ha-1), which was 4-5% higher than April 20, 17-18% higher than May 10 and 36-46% higher than May 30 sown crop. This increase in seed cotton yield was due to congenial weather conditions which resulted in extended phenophases, better growth attributes like plant height and leaf area index, improved yield attributes like monopods plant-1, sympods plant-1, bolls plant-1 and boll weight that lead to higher seed cotton yield. Results also confirmed the outperformance of Bt hybrids in comparison to non-Bt genotype. The Bt cotton sown in the month of April was found to give higher seed cotton yield as compared to its non-Bt version. [ABSTRACT FROM AUTHOR]

Published
2023
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137. Overview of recent experimental results from the ADITYA-U tokamak

Author

Tanna, R.L., primary, Macwan, Tanmay, additional, Ghosh, J., additional, Jadeja, K.A., additional, Kumar, Rohit, additional, Aich, S., additional, Patel, K.M., additional, Raj, Harshita, additional, Singh, Kaushlender, additional, Dolui, Suman, additional, Kumar, Ankit, additional, Shukla, B.K., additional, Chattopadhyay, P.K., additional, Makwana, M.N., additional, Shah, K.S., additional, Gupta, S., additional, Balakrishnan, V., additional, Gupta, C.N., additional, Panchal, V.K., additional, Edappala, Praveenlal, additional, Arambhadiya, B., additional, Shah, Minsha, additional, Gautam, Pramila, additional, Raulji, V., additional, Shukla, Praveena, additional, Rajpal, R., additional, Nagora, U.C., additional, Patel, Kiran, additional, Yadava, Nandini, additional, Patel, S., additional, Ramaiya, N., additional, Chowdhuri, M.B., additional, Manchanda, R., additional, Dey, R., additional, Shukla, G., additional, Shah, K., additional, S, Varsha, additional, Raval, J., additional, Purohit, S., additional, Tahiliani, K., additional, Kumawat, D., additional, Jha, S.K., additional, Bisai, N., additional, Atrey, P.K., additional, Pathak, S.K., additional, Gupta, M.K., additional, Gopalkrishana, M.V., additional, Doshi, B.R., additional, Sharma, Deepti, additional, Srinivasan, R., additional, Raju, D., additional, Chauhan, Chetna, additional, Saxena, Y.C., additional, Sen, Abhijit, additional, Pal, R., additional, and Chaturvedi, S., additional

Published
2022
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