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1. A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

Author

Li, S., Spitz, N., Ghantous, A., Abrishamcar, S., Reimann, B., Marques, I., Silver, M.J., Aguilar-Lacasaña, S., Kitaba, N., Rezwan, F.I., Röder, Stefan, Sirignano, L., Tuhkanen, J., Mancano, G., Sharp, G.C., Metayer, C., Morimoto, L., Stein, D.J., Zar, H.J., Alfano, R., Nawrot, T., Wang, C., Kajantie, E., Keikkala, E., Mustaniemi, S., Ronkainen, J., Sebert, S., Silva, W., Vääräsmäki, M., Jaddoe, V.W.V., Bernstein, R.M., Prentice, A.M., Cosin-Tomas, M., Dwyer, T., Håberg, S.E., Herceg, Z., Magnus, M.C., Munthe-Kaas, M.C., Page, C.M., Völker, M., Gilles, M., Send, T., Witt, S., Zillich, L., Gagliardi, L., Richiardi, L., Czamara, D., Räikkönen, K., Chatzi, L., Vafeiadi, M., Arshad, S.H., Ewart, S, Plusquin, M., Felix, J.F., Moore, S.E., Vrijheid, M., Holloway, J.W., Karmaus, W., Herberth, Gunda, Zenclussen, Ana Claudia, Streit, F., Lahti, J., Hüls, A., Hoang, T.T., London, S.J., Wiemels, J.L., Li, S., Spitz, N., Ghantous, A., Abrishamcar, S., Reimann, B., Marques, I., Silver, M.J., Aguilar-Lacasaña, S., Kitaba, N., Rezwan, F.I., Röder, Stefan, Sirignano, L., Tuhkanen, J., Mancano, G., Sharp, G.C., Metayer, C., Morimoto, L., Stein, D.J., Zar, H.J., Alfano, R., Nawrot, T., Wang, C., Kajantie, E., Keikkala, E., Mustaniemi, S., Ronkainen, J., Sebert, S., Silva, W., Vääräsmäki, M., Jaddoe, V.W.V., Bernstein, R.M., Prentice, A.M., Cosin-Tomas, M., Dwyer, T., Håberg, S.E., Herceg, Z., Magnus, M.C., Munthe-Kaas, M.C., Page, C.M., Völker, M., Gilles, M., Send, T., Witt, S., Zillich, L., Gagliardi, L., Richiardi, L., Czamara, D., Räikkönen, K., Chatzi, L., Vafeiadi, M., Arshad, S.H., Ewart, S, Plusquin, M., Felix, J.F., Moore, S.E., Vrijheid, M., Holloway, J.W., Karmaus, W., Herberth, Gunda, Zenclussen, Ana Claudia, Streit, F., Lahti, J., Hüls, A., Hoang, T.T., London, S.J., and Wiemels, J.L.

Abstract

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.

Published
2024

4. Parental preconception BMI trajectories from childhood to adolescence and asthma in the future offspring.

Author

Bowatte G., Bui D.S., Priyankara S., Lowe A.J., Perret J.L., Lodge C.J., Hamilton G.S., Erbas B., Thomas P., Thompson B., Schlunssen V., Martino D., Holloway J.W., Svanes C., Abramson M.J., Walters E.H., Dharmage S.C., Bowatte G., Bui D.S., Priyankara S., Lowe A.J., Perret J.L., Lodge C.J., Hamilton G.S., Erbas B., Thomas P., Thompson B., Schlunssen V., Martino D., Holloway J.W., Svanes C., Abramson M.J., Walters E.H., and Dharmage S.C.

Abstract

Background: Recent evidence suggests that parental exposures before conception can increase the risk of asthma in offspring. Objective(s): We investigated the association between parents' preconception body mass index (BMI) trajectories from childhood to adolescence and subsequent risk of asthma in their offspring. Method(s): Using group-based trajectory modeling from the Tasmanian Longitudinal Health Study, we identified BMI trajectories for index participants (parents) when aged 4 years to 15 years. Multinomial regression models adjusted for potential confounders were utilized to estimate the association between these early-life parents' BMI trajectories and asthma phenotypes in their subsequent offspring. Result(s): The main analysis included 1822 parents and 4208 offspring. Four BMI trajectories from age 4 years to 15 years were identified as the best-fitting model: low (8.8%), normal (44.1%), above normal (40.2%), and high (7.0%). Associations were observed between father's high BMI trajectory and risk of asthma in offspring before the age of 10 years (relative risk ratio [RRR] =1.70 [95% CI = 0.98-2.93]) and also asthma ever (RRR = 1.72 [95% CI = 1.00-2.97]), especially allergic asthma ever (RRR = 2.05 [95% CI = 1.12-3.72]). These associations were not mediated by offspring birth weight. No associations were observed for maternal BMI trajectories and offspring asthma phenotypes. Conclusion(s): This cohort study over 6 decades of life and across 2 generations suggests that the high BMI trajectory in fathers, well before conception, increased the risk of asthma in their offspring.Copyright © 2022 American Academy of Allergy, Asthma & Immunology

Published
2022

8. Path-loss characteristics of urban wireless channels

Author

Herring, K.T., Holloway, J.W., Staelin, D.H., and Bliss, D.W.

Subjects
Attenuation -- Analysis, Fading channels -- Evaluation, City planning -- Technology application, Mobile communication systems -- Research, Wireless communication systems -- Research, Wireless technology, Technology application, Business, Computers, Electronics, Electronics and electrical industries
Published
2010

9. DNA methylation and body mass index from birth to adolescence: meta-analyses of epigenome-wide association studies

Author

Vehmeijer, F.O.L. (Florianne O.L.), Küpers, A.M. (Marlijn), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Lent, S. (Samantha), Jima, D.D. (Dereje D.), Tindula, G. (Gwen), Reese, S.E. (Sarah E.), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F.I. (Faisal I.), Melton, P.E. (Philip E.), Nohr, C. (Christian), Escaramís, G. (Geòrgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S.T. (Samuli T.), Gao, L. (Lu), Ross, J.P. (Jason P.), Starling, A.P. (Anne P.), Holloway, J.W. (John W.), Yousefi, P. (Paul), Aasvang, G.M. (Gunn Marit), Beilin, L.J. (Lawrence), Bergström, A. (Anna), Binder, E.B. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (B.), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Håberg, S.E. (Siri E), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, C.A. (Christian), Langhendries, J.P. (Jean Paul), Lepeule, J. (Johanna), Magnus, M.C. (Maria C.), Maguire, R.L. (Rachel L.), Molloy, P.L. (Peter L.), Poppelaars-Monnereau, C. (Claire), Mori, T.A. (Trevor A.), Oken, E. (Emily), Räikkönen, K. (Katri), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J.M. (Judith), Xu, C.-J. (Cheng-Jian), Yang, I.V. (Ivana V.), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B.S. (Beverly S.), Breton, C. (Carrie), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sørensen, T.I.A. (Thorkild), Huang, R.-C. (Rae-Chi), Arshad, S.H. (Syed), Nystad, W. (Wenche), Melén, E. (Erik), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S.K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A.A. (Andrea), Relton, C.L. (Caroline), Snieder, H. (Harold), Jaddoe, V.W.V. (Vincent), Felix, J.F. (Janine), Vehmeijer, F.O.L. (Florianne O.L.), Küpers, A.M. (Marlijn), Sharp, G.C. (Gemma C.), Salas, L.A. (Lucas A.), Lent, S. (Samantha), Jima, D.D. (Dereje D.), Tindula, G. (Gwen), Reese, S.E. (Sarah E.), Qi, C. (Cancan), Gruzieva, O. (Olena), Page, C. (Christian), Rezwan, F.I. (Faisal I.), Melton, P.E. (Philip E.), Nohr, C. (Christian), Escaramís, G. (Geòrgia), Rzehak, P. (Peter), Heiskala, A. (Anni), Gong, T. (Tong), Tuominen, S.T. (Samuli T.), Gao, L. (Lu), Ross, J.P. (Jason P.), Starling, A.P. (Anne P.), Holloway, J.W. (John W.), Yousefi, P. (Paul), Aasvang, G.M. (Gunn Marit), Beilin, L.J. (Lawrence), Bergström, A. (Anna), Binder, E.B. (Elisabeth), Chatzi, L. (Leda), Corpeleijn, E. (Eva), Czamara, D. (Darina), Eskenazi, B. (B.), Ewart, S. (Susan), Ferre, N. (Natalia), Grote, V. (Veit), Gruszfeld, D. (Dariusz), Håberg, S.E. (Siri E), Hoyo, C. (Cathrine), Huen, K. (Karen), Karlsson, R. (Robert), Kull, C.A. (Christian), Langhendries, J.P. (Jean Paul), Lepeule, J. (Johanna), Magnus, M.C. (Maria C.), Maguire, R.L. (Rachel L.), Molloy, P.L. (Peter L.), Poppelaars-Monnereau, C. (Claire), Mori, T.A. (Trevor A.), Oken, E. (Emily), Räikkönen, K. (Katri), Rifas-Shiman, S.L. (Sheryl), Ruiz-Arenas, C. (Carlos), Sebert, S. (Sylvain), Ullemar, V. (Vilhelmina), Verduci, E. (Elvira), Vonk, J.M. (Judith), Xu, C.-J. (Cheng-Jian), Yang, I.V. (Ivana V.), Zhang, H. (Hongmei), Zhang, W. (Weiming), Karmaus, W. (Wilfried), Dabelea, D. (Dana), Muhlhausler, B.S. (Beverly S.), Breton, C. (Carrie), Lahti, J. (Jari), Almqvist, C. (Catarina), Jarvelin, M.-R. (Marjo-Riitta), Koletzko, B. (Berthold), Vrijheid, M. (Martine), Sørensen, T.I.A. (Thorkild), Huang, R.-C. (Rae-Chi), Arshad, S.H. (Syed), Nystad, W. (Wenche), Melén, E. (Erik), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Holland, N. (Nina), Bustamante, M. (Mariona), Murphy, S.K. (Susan K.), Hivert, M.-F. (Marie-France), Baccarelli, A.A. (Andrea), Relton, C.L. (Caroline), Snieder, H. (Harold), Jaddoe, V.W.V. (Vincent), and Felix, J.F. (Janine)

Abstract

Background: DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods: We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results: DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10−7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7). Conclusions: There were only minimal associations of DNA methylation with childhood and adolescent BMI.

Published
2020
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10. Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Author

Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), Melén, E. (Erik), Merid, S.K. (Simon Kebede), Novoloaca, A. (Alexei), Sharp, G.C. (Gemma C.), Küpers, A.M. (Marlijn), Kho, A.T. (Alvin T.), Roy, R. (Ritu), Gao, L. (Lu), Annesi-Maesano, I. (Isabella), Jain, P. (Pooja), Plusquin, M. (Michelle), Kogevinas, M. (Manolis), Allard, C. (Catherine), Vehmeijer, F.O.L. (Florianne O.L.), Kazmi, N. (Nabila), Salas, L.A. (Lucas A.), Rezwan, F.I. (Faisal I.), Zhang, H. (Hongmei), Sebert, S. (Sylvain), Czamara, D. (Darina), Rifas-Shiman, S.L. (Sheryl), Melton, P.E. (Phillip E.), Lawlor, D.A. (Debbie A.), Pershagen, G. (Göran), Breton, C. (Carrie), Huen, K. (Karen), Baïz, N. (Nour), Gagliardi, L. (Luigi), Nawrot, T.S. (Tim S.), Corpeleijn, E. (Eva), Perron, P. (Patrice), Duijts, L. (Liesbeth), Nohr, C. (Christian), Bustamante, M. (Mariona), Ewart, S. (Susan), Karmaus, W. (Wilfried), Zhao, S. (Shanshan), Page, C.M. (Christian M.), Herceg, Z. (Zdenko), Jarvelin, M.-R. (Marjo-Riitta), Lahti, J. (Jari), Baccarelli, A.A. (Andrea), Anderson, D. (Denise), Kachroo, P. (Priyadarshini), Relton, C.L. (Caroline), Bergström, A. (Anna), Eskenazi, B. (B.), Soomro, M.H. (Munawar Hussain), Vineis, P. (Paolo), Snieder, H. (Harold), Bouchard, L. (Luigi), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Vrijheid, M. (Martine), Arshad, S.H. (Syed), Holloway, J.W. (John W.), Håberg, S.E. (Siri E), Magnus, P. (Per), Dwyer, T. (Terence), Binder, E.B. (Elisabeth), Demeo, D.L. (Dawn), Vonk, J.M. (Judith), Newnham, J.P. (John), Tantisira, K.G. (Kelan G.), Kull, C.A. (Christian), Wiemels, J. (Joseph), Heude, B. (Barbara), Sunyer, J. (Jordi), Nystad, W. (Wenche), Munthe-Kaas, M.C. (Monica Cheng), Räikkönen, K. (Katri), Oken, E. (Emily), Huang, R.-C. (Rae-Chi), Weiss, S.T. (Scott T.), Antó, J.M. (Josep Maria), Bousquet, J. (Jean), Kumar, A. (Ashish), Söderhäll, C. (Cilla), Almqvist, C. (Catarina), Cardenas, A. (Andres), Gruzieva, O. (Olena), Xu, C.-J. (Cheng-Jian), Reese, S.E. (Sarah E.), Kere, J. (Juha), Brodin, P. (Petter), Solomon, O. (Olivia), Wielscher, M. (Matthias), Holland, N. (Nina), Ghantous, A. (Akram), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Koppelman, G.H. (Gerard), London, S.J. (Stephanie J.), and Melén, E. (Erik)

Abstract

BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

Published
2020
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11. Preweaning growth of [F.sub.1] tropically adapted beef cattle breeds x Angus and reproductive performance of their Angus dams in arid rangeland

Author

Holloway, J.W., Warrington, B.G., Forrest, D.W., and Randel, R.D.

Subjects
Beef cattle -- Breeding, Aberdeen-Angus cattle -- Research, Rangelands -- Research, Zoology and wildlife conservation
Abstract

The objective of this study was to determine the preweaning performance of [F.sub.1] Brahman (Bos indicus)-, Senepol (Bos taurus)-, and Tuli (Sanga)-Angus calves under semiarid south Texas conditions and to evaluate the reproductive performance of their Angus dams. Four hundred eighty-nine records collected over 4 yr were analyzed. The statistical model for performance traits included the effects of breed of sire, year, sex, age of dam, and breed of sire x year. Year effects were important (P < 0.05) for performance traits but could be explained, at least partially, by differences between years in rainfall patterns. Brahman [F.sub.1] calves were 13% less (P < 0.05)vigorous at birth, 4.7 kg heavier (P < 0.05) at birth, 13.5 kg heavier (P < 0.05) at weaning, 0.25 units lower (P < 0.05) in body condition score (BCS) at weaning, and 1.75 units greater (P < 0.05) in frame score (scores of I to 9) at weaning than Tuli and Senepol [F.sub.1] calves. Senepol [F.sub.1] calves were intermediate (P < 0.05) between the Brahman and Tuli [F.sub.1] calves for birth and weaning weight but had 11% more (P < 0.05) vigor at birth than the other two crossbreds. Tuli and Senepol [F.sub.1] were similar (P > 0.05) in BCS and frame size at weaning. Males were 3.3 kg heavier (P = 0.12) at birth than females, especially for the [F.sub.1] Brahman males that were 4.5 kg heavier (P < 0.05) than their counterparts. Brahman [F.sub.1] weaned 19.9 kg heavier (P < 0.05) than the average of the other two [F.sub.1] in the year of the greatest rainfall (1994), whereas the average advantage in other years was 11.4 kg. This difference gave rise to a breed of sire x year interaction (P < 0.003). Brahman [F.sub.1] were heavier at every measurement and appeared to be later-maturing and more able to excel under good forage conditions than the other two [F.sub.1] breed types; Senepol and Tuli [F.sub.1] were similar (P > 0.05) in these respects but appeared to be more competitive in relative growth rate to the Brahman [F.sub.1] calves in years of greater nutritional stress. Angus females were observed to have a relatively low reproductive rate and high apparent fetal loss at the first (27.5%) and second (19.2%) compared with the third or later pregnancy (11.2%). Angus females that gave birth to Brahman [F.sub.1] calves had 20.1% lower (P < 0.05) pregnancy rates in the succeeding year than those that had given birth to the other two breeds. Key Words: Breeding Methods, Crossbreeding, Performance, Genotype Environment Interaction

Published
2002

14. Effects of Supplemental Feeding Interval on Adult Cows in Western Texas

Author

Huston, J.E., Lippke, H., Forbes, T.D.A., Holloway, J.W., and Machen, R.V.

Subjects
Dietary supplements -- Influence, Cows -- Health aspects, Feed utilization efficiency -- Analysis, Zoology and wildlife conservation
Abstract

Two experiments involving Brangus and Hereford x Brangus cows (3 to 10 yr) were conducted at four locations in western Texas to determine the effects of supplemental feeding interval on serum urea nitrogen (SUN) patterns, intake of supplement and forage, and winter changes in live body weight and condition score. Treatments were control (Control; no supplemental feed) and the equivalent of .91 kg/d of cottonseed meal (CSM) fed daily (Daily), three times per week (3T/WK), or one time per week (WK). At each location, one pasture group was given all four treatments (four cows/treatment) using Calan gates. In Exp. 1, conducted in 1994-95, blood samples were obtained for determining SUN during the last week of the study. Experiment 2, conducted in 1995-96, included both an individually fed herd and four additional herds at each location that were group-fed the four treatments. Experiment 2 included estimates of intakes of both CSM and forage in both individually fed and group-fed herds. A bolus containing chromium (Cr-bolus) was used to estimate fecal output in the individually fed cows. A double marker technique was used to determine total (Cr-bolus) and CSM (Yb) intakes in the group-fed cows. Data included initial and final cow weights and condition scores (Exp. 1 and 2), SUN patterns (Exp. 1), and supplement, forage, and total intakes (Exp. 2). Feeding CSM to range cows increased SUN concentrations (Exp. 1), reduced losses in live body weight and body condition score (Exp. 1 and 2), and tended to decrease forage intake by the approximate amount of the supplement (Exp. 2). Generally, providing supplement as infrequently as once per week reduced losses in live body weight and body condition score compared with control and was as effective as once daily supplementation. For the group-fed cows, supplement intake, forage intake, and live body weight change were more variable within groups with once daily feeding than when supplement was fed less frequently. These data indicate that feeding as infrequently as one time per week can be effective nutrition management for adult cows grazing native range. Key Words: Supplements, Feeding Frequency

Published
1999

15. Maternal Nrf1 and gluthathione-S-transferase polymorphisms do not modify associations of prenatal tobacco smoke exposure with asthma and lung function in school-aged children

Author

Henderson, A.J., Newson, R.B., Rose-Zerilli, M., Ring, S.M., Holloway, J.W., and Shaheen, S.O.

Subjects
Passive smoking -- Research, Asthma in children -- Genetic aspects, Asthma in children -- Risk factors, Asthma in children -- Development and progression, Asthma in children -- Research, Genetic polymorphisms -- Research, Glutathione transferase -- Genetic aspects, Glutathione transferase -- Research, Health
Published
2010

17. Genetic susceptibility to the respiratory effects of air pollution

Author

Yang, I.A., Fong, K.M., Zimmerman, P.V., Holgate, S.T., and Holloway, J.W.

Subjects
Respiratory tract diseases -- Genetic aspects, Respiratory tract diseases -- Risk factors, Air pollution -- Genetic aspects, Genetic susceptibility -- Reports, Oxidative stress -- Genetic aspects, Health
Published
2009

18. Genetic susceptibility to the respiratory effects of air pollution

Author

Yang, I.A., Fong, K.M., Zimmerman, P.V., Holgate, S.T., and Holloway, J.W.

Subjects
Genetic susceptibility -- Research, Air pollution -- Health aspects, Respiratory tract diseases -- Risk factors, Respiratory tract diseases -- Genetic aspects, Health
Published
2008

19. Physiological adaptations in adipose tissue of Brahman vs Angus heifers

Author

Sprinkle, J.E., Hansard, H.S., Warrington, B.G., Holloway, J.W., Wu, G., and Smith, S.B.

Subjects
Adipose tissues -- Physiological aspects, Adaptation (Physiology) -- Research, Zebus -- Physiological aspects, Aberdeen-Angus cattle -- Physiological aspects, Heifers -- Physiological aspects, Zoology and wildlife conservation
Abstract

Nonpregnant yearling Brahman (n = 12) and Angus (n = 12) heifers were equally allocated to two dietary treatments in a replicated study to examine responses in lipid metabolism to nutritional treatments consisting of a moderate energy diet (2.0 Mcal ME/kg) fed at maintenance and a 2.5 x maintenance high-energy diet (2.4 Mcal ME/kg) fed for 30 d. In vitro lipogenesis and the activities of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) were determined in perianal subcutaneous adipose tissue biopsies at the start and end of the trial. At the start of the trial, breeds had similar (P > .10) rates of lipogenesis and LPL activity. Brahman had greater (P < .05) HSL activity than Angus at the start of the trial and tended (P < .07) to have greater HSL activity at the end. Diet did not influence (P > .10) HSL activity. Heifers on the high-energy, higher-intake diet had greater lipogenesis (P < .001) and LPL activity (P < .01) than those on the moderate-energy diet. Inclusion of body condition score (BCS) nested within breed as a covariate explained breed differences for lipogenesis (P < .05). Thus, by including the covariate, the two breeds had similar (P > .10) rates of lipogenesis at the end of the trial. When adjusted for BCS nested within breed, Brahman had greater (P < .05) LPL activity than Angus. Key Words: Beef Cattle, Breeds, Lipoproteins, Triacylglycerol Lipase, Lipogenesis

Published
1998

20. Adipose tissue partitioning of limit-fed beef cattle and beef cattle with ad libitum access to feed differing in adaptation to heat

Author

Sprinkle, J.E., Ferrell, C.L., Holloway, J.W., Warrington, B.G., Greene, L.W., Wu, G., and Stuth, J.W.

Subjects
Beef cattle -- Physiological aspects, Adipose tissues -- Research, Adaptation (Physiology) -- Research, Fat metabolism -- Research, Lipoprotein lipase -- Physiological aspects, Zoology and wildlife conservation
Abstract

We compared fat distribution and lipoprotein lipase (LPL) activity in steers differing in adaptability to the subtropics. Steers were fed a grain diet (3.13 Mcal ME/kg DM) at limited (150 kcal ME[multiplied by][kg.sup.-.75][multiplied by][d.sup.-1]; .23 kg ADG) or ad libitum levels for 140 d, then slaughtered. Sixteen British- (8 Angus, 8 Hereford; S), 16 Boran- (R), 16 Brahman- (B), and 16 Tuli- (T) cross steers from MARC III composite cows were used. Adipose tissue samples from perirenal, omental, and subcutaneous depots were analyzed for LPL activity. Carcass measurements including omental, external, and seam fat trim from 1/2 of the carcass were measured. Subcutaneous fat had greater (P < .05) LPL activity than fat from the other depots. Generally, there were no differences (P > .05) in fat distribution for steers fed at limited levels. Means for ADG, slaughter weights, carcass weights, yield grades, and carcass lipid weights for S and B fed for ad libitum intake were greater (P < .05) than those for T and R. Marbling was greatest (P < .05) for S and did not differ (P > .05) for the other breeds with ad libitum intake. Factor analysis of fat depots for animals with ad libitum intake indicated that Bos taurus cattle differing in adaptation to heat deposited fat differently; S deposited greater (P < .05) proportions of carcass fat and T deposited greater (P < .05) proportions of internal fat. It seems that accumulation of internal fat is detrimental for ADG for Bos taurus cattle. Key Words: Lipoprotein Lipase, Beef Cattle, Breeds, Heat, Adipose Tissue

Published
1998

23. Animal performance and fleece characteristics of Angora goats maintained on western and southern Texas rangeland

Author

Lupton, C.J., Huston, J.E., Holloway, J.W., Warrington, B.G., Waldron, D.F., Thompson, P.V., Pfeiffer, F.A., and Qi, K.

Subjects
Angora goat -- Research, Mohair -- Research, Zoology and wildlife conservation
Abstract

Two hundred castrated male Angora goats (18 mo of age) were divided equally between rangeland sites in the oak savannah of the Edwards Plateau (EP) and the mixed-brush shrublands of the South Texas Plains (STP) for 5 yr to study influence of environment and age on body weight (BW), mohair production, and mohair fiber characteristics. Goats were grazed on rangeland typical of the respective regions and were given typical management that included shearing in February and July or August of each year. Shorn goats were weighed and individual fleeces were measured for grease weight (GFW), clean yield (CMFP), average fiber diameter (AFD), and proportion of medullated fibers, med (MFP) and kemp (KFP). Rainfall and maximum and minimum temperatures were recorded daily at each site. The AFD (P = .01) and its associated SD (P [less than] .001) and kemp levels (P = .03) were all higher at the STP than at the EP site (39.4 vs 37.9 [[micro]meter], 10.4 vs 11.1 [[micro]meter], and .80 vs .68%, respectively). Angora goats at EP weighed less (38.1 vs 41.7 kg, P = .03), and sheared less (1.90 vs 2.22 kg, P = .01), finer (36.4 vs 39.3 [[micro]meter], P [less than] .001), and less kempy (.52 vs .84%, P [less than] .001) mohair at the February shearing than at the August shearing. No seasonal differences in body weight or in mohair production or quality were apparent at STP. The proportions of total variation in grease mohair production (30.6%), CMFP (22.2%), and AFD (15.7%) due to year effects were two to three times greater at STP than at EP. In contrast, year effects were responsible for only a small proportion (2.2 to 4.6%) of the variation in medullated fibers. The effects of rainfall accumulation within specific 6-mo growing periods were positive for BW, GFW, CFW, AFD, SD of AFD and MFP and negative for CMFP and KFP. Only the rainfall effects on SD of AFD and medullated fibers were significant (P [less than] .05). The effects of age were positive for BW (P [less than] .001), CMFP (P = .046), AFD (P [less than] .001), MFP (P = .014), and KFP (P = .084) and negative for GFW (P = .046) and CFW (P = .107). This study documents influence of environment and age of goats on body weight, mohair production, and fiber characteristics. Key Words: Age, Angora, Goats, Body Weight, Environment, Mohair

Published
1996

24. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns Findings From the Pregnancy and Childhood Epigenetics Consortium

Author

Kazmi, N., Sharp, G.C. (Gregory), Reese, SE, Vehmeijer, F.O., Lahti, J. (Jari), Page, CM, Zhang, W.M., Rifas-Shiman, S.L. (Sheryl L.), Rezwan, F.I., Simpkin, A.J., Burrows, K., Richardson, T.G., Ferreira, D. L. S., Fraser, A, Harmon, Q.E., Zhao, S.S., Jaddoe, V.W.V. (Vincent), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Magnus, M.C., Håberg, S.E. (Siri E), Nystad, W. (Wenche), Nohr, C. (Christian), Starling, A.P., Kechris, K.J., Yang, I.V., Demeo, D.L. (Dawn), Litonjua, AA, Baccarelli, A., Oken, E. (Emily), Holloway, J.W. (John), Karmaus, W, Arshad, S.H. (Syed), Dabelea, D., Sorensen, H.G., Laivuori, H, Raikkonen, K. (Katri), Felix, J.F. (Janine), London, S.J. (Stephanie), Hivert, M.-F. (Marie-France), Gaunt, T.R. (Tom), Lawlor, D.A. (Debbie), Relton, C.L. (Caroline), Kazmi, N., Sharp, G.C. (Gregory), Reese, SE, Vehmeijer, F.O., Lahti, J. (Jari), Page, CM, Zhang, W.M., Rifas-Shiman, S.L. (Sheryl L.), Rezwan, F.I., Simpkin, A.J., Burrows, K., Richardson, T.G., Ferreira, D. L. S., Fraser, A, Harmon, Q.E., Zhao, S.S., Jaddoe, V.W.V. (Vincent), Czamara, D. (Darina), Binder, E.B. (Elisabeth), Magnus, M.C., Håberg, S.E. (Siri E), Nystad, W. (Wenche), Nohr, C. (Christian), Starling, A.P., Kechris, K.J., Yang, I.V., Demeo, D.L. (Dawn), Litonjua, AA, Baccarelli, A., Oken, E. (Emily), Holloway, J.W. (John), Karmaus, W, Arshad, S.H. (Syed), Dabelea, D., Sorensen, H.G., Laivuori, H, Raikkonen, K. (Katri), Felix, J.F. (Janine), London, S.J. (Stephanie), Hivert, M.-F. (Marie-France), Gaunt, T.R. (Tom), Lawlor, D.A. (Debbie), and Relton, C.L. (Caroline)

Abstract

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

Published
2019
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25. Influence of calf genotype on colostral immunoglobulins in Bos taurus and Bos indicus cows and serum immunoglobulins in their calves

Author

Vann, R.C., Holloway, J.W., Carstens, G.E., Boyd, M.E., and Randel, R.D.

Subjects
Genotype -- Research, Cows -- Physiological aspects, Immunoglobulins -- Physiological aspects, Colostrum -- Physiological aspects, Zoology and wildlife conservation
Abstract

Purebred Bos indicus calves are documented to have lower survival rates than Bos taurus calves. Thus, this study was designed to investigate the possibility that this decreased survival rate may be attributed to dam colostral immunoglobulin (Ig) concentrations and subsequent calf serum Ig concentrations. The specific objective was to determine the effect of breed type of calf on colostrum production, immunoglobulin concentrations in colostrum and calf serum, and availability and absorption efficiency of Ig. Brahman (B) and Angus (A) cattle were reciprocally mated to produce calves of the following types: A x A (n=8),A x B (n=9), B x B (n=11), and B x A (n = 11). At birth, calves were separated from their dams and a blood sample was collected before feeding pooled colostrum (30 mL/kg birth weight) at 1 and 6 h of age. From 6 to 12 h of age, each calf was placed in a box that allowed interaction with the dam but prevented suckling. At 12 h of age, each calf was fed its dam's colostrum and placed with the dam. Additional blood samples were collected at 12, 24, and 48 h after birth. Serum and colostrum samples were analyzed for IgG, Ig[G.sub.1], Ig[G.sub.2], IgM, and IgA using single radial immunodiffusion (RID) assay techniques. The cows were hand-milked after induction of milk letdown with oxytocin at i and 12 h after calving. Colostrum volume was recorded, and samples were collected. Brahman cows produced more (P < .001) colostrum at 1 and 12 h than A cows. Total Ig concentrations were obtained by summing IgG, Ig[G.sub.1], Ig[G.sub.2], IgM, and IgA concentrations. Total Ig (P < .02), IgG (P < .005), and IgA (P < .01) concentrations in colostrum were greater in cows producing crossbred calves. Total Ig (P < .006), IgG (P < .02), Ig[G.sub.1] (P < .004), and Ig[G.sub.2] (P < .02) available in colostrum were affected by B x B and A x B breed types of calf. Brahman cows had more Ig available at 1 and 12 h than A cows due to increased production of colostrum. Breed type influenced colostral Ig in cattle. Serum concentrations of total Ig, IgG, Ig[G.sub.1], Ig[G.sub.2], IgM, and IgA in the calf and efficiency of absorption at 6 and 12 h were not affected by breed type, sex of calf, or any interaction. Key Words: Bovine, Colostrum, Breed, Absorption Efficiency, Immunoglobulins

Published
1995

26. Influence of maternal and service-sire breed on serum progesterone and estrogen before calving and plasma 13,14-dihydro-15-keto-prostaglandin F2alpha after calving

Author

Lammoglia, M.A., Holloway, J.W., Lewis, A.W., Neuendorff, D.A., and Randel, R.D.

Subjects
Progesterone -- Research, Estrogen -- Research, Serum -- Research, Plasma diagnostics -- Research, Beef cattle -- Breeding, Livestock -- Research, Zoology and wildlife conservation
Abstract

Effects of breed of service sire and cow on birth weight and prepartum and postpartum endocrine function were studied in multiparous Brahman (n = 20) and Angus (n = 20) cows bred to Brahman or Angus bulls. Before calving, blood samples were collected on d 34 to 28, 27 to 21, 20 to 14, and 13 to 7, and after calving, samples were collected from d 0 to 7. Progesterone ([P.sub.4]), estrogen ([E.sub.2]), and 13,14-dihydro-15-keto-prostaglandin [F.sub.2[Alpha]] (PGFM) were quantified with RIA. Calves born to Brahman were smaller (P < .05) than calves born to Angus cows. Prepartum concentrations of [P.sub.4] were greater in Angus cows and decreased more rapidly near parturition than in Brahman cows (breed of dam X period; P < .03). Cows bearing bull calves had greater concentrations of [P.sub.4] on d 20 to 14 before calving than cows bearing heifer calves (sex of calf X period; P < .04). Prepartum [E.sub.2] was influenced (P < .05) by the breed of dam X breed of sire X period interaction. The ratio of [P.sub.4]:[E.sub.2] tended to decrease more in Angus than in Brahman cows near parturition (breed of dam X period; P < .09). Postpartum PGFM tended to be influenced (P < .08) by breed of dam X breed of sire; from d 3 to 5, Brahman cows bred to Angus bulls tended (P < .08) to have greater PGFM than Brahman cows bred to Brahman bulls or than Angus cows bred to Brahman or Angus bulls. On d I after calving, cows producing heifer calves tended (P < .09) to have greater PGFM concentrations than cows producing bull calves. Hormonal profiles before and after calving were influenced by breed of service sire and cow, sex of calf, and sampling period. Key Words: Breeds, Progesterone, Estrogen, Prostaglandins, Cattle

Published
1995

27. Herbage allowance x yearling heifer phenotype interactions for preweaning calf growth on humid pasture and semiarid rangeland

Author

Holloway, J.W., Rouquette, F.M., Jr., Warrington, B.G., Long, C.R., Owens, M.K., Forrest, D.W., and Baker, J.F.

Subjects
Calves -- Genetic aspects, Phenotype -- Research, Grasses -- Health aspects, Body size -- Research, Zoology and wildlife conservation
Abstract

Preweaning growth data were obtained during 4 yr on 349 Braford-sired calves from Brahman-Hereford [F.sub.1] first-calf females. These females were allotted to either semiarid rangeland (Uvalde) or humid improved pasture (Overton) as weanlings and to one of four herbage allowance levels at each location as yearlings. Females were wintered on systems in local industry practice and maintained on various allotted herbage levels both as yearlings and during first lactation. The desired range in herbage allowance (400 to 2,800 kg of DM per 100 kg of BW at Uvalde and 80 to 460 kg of DM per 100 kg of BW at Overton) was accomplished by adjusting stocking rate monthly from April to weaning (October). Herbage allowance and yearling heifer characteristics (hook height, condition score, or weight) were treated as continuous, independent variables in regression analyses. Preweaning daily gain responded to increased herbage allowance differently for the two locations. Generally, at Overton, herbage allowance influenced suckling calf growth to a greater extent than for the [F.sub.1] yearling variables, but at Uvalde this trend was reversed. Heifers with larger yearling heights had first calves that grew faster to weaning for both locations and all herbage allowances, although the relationship was stronger for greater herbage allowances at Overton (herbage allowance x yearling weight interaction, P [is less than] .07). This interaction was not detected (P [is greater than] .15) at Uvalde. Interactions between herbage allowance and yearling condition score were detected (P [is less than] .05) at both Overton and Uvalde, but these interactions were different (P [is less than] .15) at the two locations. At Uvalde, calf daily gain increased more with increased herbage allowance for females that had greater yearling condition than for those with less condition. At Overton, the opposite effect was observed: yearlings of lower condition had calves that benefited the most. For humid improved pastures, yearling females with lower condition scores had calves that grew faster, especially at high herbage allowances. In contrast, for semiarid rangeland, fatter yearling females had calves that grew faster, especially at high herbage allowance.

Published
1994

28. ADAM 33: just another asthma gene or a breakthrough in understanding the origins of bronchial hyperresponsiveness?

Author

Holgate, S.T., Davies, D.E., Murphy, G., Powell, R.M., and Holloway, J.W.

Subjects
Asthma -- Genetic aspects -- Development and progression, Respiratory allergy -- Genetic aspects -- Development and progression, Health, Development and progression, Genetic aspects
Abstract

ADAM 33, the latest of the ADAM proteins to be described, has been identified as a major susceptibility gene in asthma linked to bronchial hyperresponsiveness. It provides an important breakthrough [...]

Published
2003

29. Allelic association and functional studies of promoter polymorphism in the leukotriene C4 synthase gene (LTC4S) in asthma. (Asthma)

Author

Sayers, I., Barton, S., Rorke, S., Beghe, B., Hayward, B., Eerdewegh, P. Van, Keith, T., Clough, J.B., Ye, S., Holloway, J.W., Sampson, A.P., and Holgate, S.T.

Subjects
Genetic polymorphisms -- Physiological aspects -- Genetic aspects, Leukotrienes -- Genetic aspects -- Physiological aspects -- Synthesis, Asthma -- Genetic aspects, Health, Physiological aspects, Genetic aspects
Abstract

Background: LTC4 synthase is essential for the production of cysteinyl leukotrienes (Cys-LT), critical mediators in asthma. We have identified a novel promoter polymorphism at position -1072 (G/A) and a -444 [...]

Published
2003

30. Herbage allowance x yearling heifer phenotype interactions for the growth of Brahman-Hereford F(sub 1) first-calf females grazing humid pasture and semiarid rangeland

Author

Holloway, J.W., Warrington, B.G., Rouquette, F.M., Jr., Long, C.R., Owens, M.K., and Baker, J.F.

Subjects
Heifers -- Physiological aspects, Zebus -- Growth, Hereford cattle -- Growth, Grasses -- Physiological aspects, Pastures -- Physiological aspects, Rangelands -- Physiological aspects, Zoology and wildlife conservation
Abstract

Growth data were collected over 4 yr from 349 Brahman-Hereford F(sub 1), first-calf, lactating females that had been allotted as weanlings to either semiarid extensive rangeland (Uvalde) or humid improved Bermudagrass pasture (Overton) and to one of four herbage allowance levels at each location as yearlings. Heifers were wintered according to systems in local practice and maintained on allotted forage levels both as yearlings and during their first lactation. Heifers were bred to Braford bulls to calve as 2-yr-olds in January to March. Herbage allowance (400 to 2,800 kg of DM/100 kg BW at Uvalde and 80 to 460 kg of DM/100 kg BW at Overton) was maintained by adjusting stocking density monthly from April to weaning (October). Herbage allowance and yearling heifer hook height, condition score, or weight (taken on April 15) were continuous independent variables in regression analyses. Final heifer weight, height, and condition responses to increased herbage allowances were related to yearling phenotypes differently (P < .01) for the two locations. At Uvalde, yearling condition score interactions were especially important in that heifers that had more condition (especially those > 5 for 1 to 10 with 10 = fattest) as yearlings retained more (P < .05) weight and condition and grew more (P > .05) in height than did those of lower yearling condition. These females also responded to increased herbage allowance by gaining advantage (P < .05) in these variables, whereas those of lower yearling condition made smaller advances. At Overton, yearling condition played little role in subsequent growth. The yearling variable that had the greatest interactive effect was height. Shorter yearling heifers (< 123 cm) responded (P < .07) to increased herbage allowance so that they had greater final condition and grew more rapidly in height than those taller as yearlings.

Published
1993

32. Relation of FTO gene variants to fetal growth trajectories: Findings from the Southampton Women's survey

Author

Barton, S.J., Mosquera, M., Cleal, J.K., Fuller, A.S., Crozier, S.R., Cooper, C., Inskip, H.M., Holloway, J.W., Lewis, R.M., and Godfrey, K.M.

Subjects
Placental amino acid transporter expression, endocrine system diseases, Reproductive Medicine, Fetal growth trajectories, Obstetrics and Gynaecology, nutritional and metabolic diseases, MC4R genotype, pathological conditions, signs and symptoms, Placental FTO expression, FTO genotype, Developmental Biology
Abstract

IntroductionPlacental function is an important determinant of fetal growth, and fetal growth influences obesity risk in childhood and adult life. Here we investigated how FTO and MC4R gene variants linked with obesity relate to patterns of fetal growth and to placental FTO expression.MethodsSouthampton Women's Survey children (n = 1990) with measurements of fetal growth from 11 to 34 weeks gestation were genotyped for common gene variants in FTO (rs9939609, rs1421085) and MC4R (rs17782313). Linear mixed-effect models were used to analyse relations of gene variants with fetal growth.ResultsFetuses with the rs9939609 A:A FTO genotype had faster biparietal diameter and head circumference growth velocities between 11 and 34 weeks gestation (by 0.012 (95% CI 0.005 to 0.019) and 0.008 (0.002–0.015) standard deviations per week, respectively) compared to fetuses with the T:T FTO genotype; abdominal circumference growth velocity did not differ between genotypes. FTO genotype was not associated with placental FTO expression, but higher placental FTO expression was independently associated with larger fetal size and higher placental ASCT2, EAAT2 and y + LAT2 amino acid transporter expression. Findings were similar for FTO rs1421085, and the MC4R gene variant was associated with the fetal growth velocity of head circumference.DiscussionFTO gene variants are known to associate with obesity but this is the first time that the risk alleles and placental FTO expression have been linked with fetal growth trajectories. The lack of an association between FTO genotype and placental FTO expression adds to emerging evidence of complex biology underlying the association between FTO genotype and obesity.

Published
2016
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33. Forage availability x heifer phenotype interactions for Brahman-Hereford F1 yearling heifers grazing humid pasture and semiarid rangeland

Author

Holloway, J.W., Warrington, B.G., Rouquette, F.M., Jr., Long, C.R., Owens, M.K., and Baker, J.F.

Subjects
Heifers -- Food and nutrition, Pasture ecology -- Influence, Rangelands -- Influence, Phenotype -- Research, Zoology and wildlife conservation
Abstract

Yearling heifer growth data were obtained during 4 yr for 524 heifers allotted to either humid bermudagrass pastures (Overton) or semiarid rangeland (Uvalde). Each year, heifers were allotted on April 15 to four forage availability levels (400 to 2,800 kg of DM per 100 kg of BW at Uvalde and 80 to 260 kg of DM per 100 kg of BW at Overton) maintaned by varying the stocking rate monthly until mid-October of each year. Forage availability and yearlig heifer characteristics (weight, condition score, and height at hooks, taken on April 15) were treated as continuous variables in regression analyses. Final heifer weight, height, and condition responses to increased forage allowance were related to yearling phenotypes differently for the two locations. Generally, at Overton, forage availability influenced final characteristics to a greater extent than did yearling variables, whereas the trend was the opposite at Uvalde. At Uvalde, the yearlig characteristic that had the largest effect on performance was height at hooks. Yearlings with large frames benefited from increased forage allowance by accumulating body fat at a faster rate than those with small frames. In contrast, at Overton, the yearling characteristic that had the largest effect on performance was condition. Fat heifers responded to increased forage availability to gain even greater advantages in fatness at the expense of potential growth in height and, thus, achieved early maturation. Yearling phenotypes were more humid, improved pastures than for semiarid rangeland. Key Words: Phenotype Environment Interaction, Adaptation, Heifers, Growth, Forage Availabity, A four-year experimental study on heifers indicated that phenotype shows greater adaptation to forage availability for cattle grazing on humid pastures than for cattle grazing on semi arid regions. Heifers were allotted to one of the four feeding systems, each year. At the end of the year heifer traits such as, weight and height at hooks, were measured to assess the interaction between phenotypic traits and forage availability. Forage availability affected the general characteristics of animals grazing on humid pastures of Overton while the opposite was observed for animals grazing on semiarid pastures of Uvalde.

Published
1992

34. Functional Translation of IL33 Locus Polymorphisms Into Altered Epithelial Cell Function Underlying Asthma

Author

Ketelaar, M., primary, Portelli, M.A., additional, Dijk, F.N., additional, Faiz, A., additional, Shrine, N., additional, Hankinson, J., additional, Bhaker, S., additional, Henry, A.P., additional, Billington, C.K., additional, Shaw, D., additional, Johnson, S.R., additional, Benest, A.V., additional, Pogson, Z.E.K., additional, Fogarty, A., additional, McKeever, T.M., additional, Singapuri, A., additional, Heaney, L., additional, Mansur, A., additional, Gaudhuri, R., additional, Thomson, N.C., additional, Holloway, J.W., additional, Lockett, G.A., additional, Howarth, P.H., additional, Niven, R., additional, Simpson, A., additional, Tobin, M.D., additional, Postma, D.S., additional, Hall, I.P., additional, Wain, L.V., additional, Brightling, C.E., additional, Obeidat, M., additional, Sin, D.D., additional, van den Berge, M., additional, Koppelman, G.H., additional, Sayers, I., additional, and Nawijn, M.C., additional

Published
2019
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35. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

Author

Beaumont, R.N. (Robin N.), Warrington, N.M. (Nicole), Cavadino, A. (Alana), Tyrrell, A.W.R., Nodzenski, M. (Michael), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Richmond, R.C. (Rebecca C.), Paternoster, L. (Lavinia), Bradfield, J.P. (Jonathan), Kreiner-Møller, E. (Eskil), Huikari, V. (Ville), Metrustry, S. (Sarah), Lunetta, K.L. (Kathryn), Painter, J.N. (Jodie N.), Hottenga, J.J. (Jouke Jan), Allard, C. (Catherine), Barton, S.J. (Sheila), Espinosa, A. (Ana), Marsh, J.A. (Julie), Potter, C. (Catherine), Zhang, G. (Ge), Ang, W.Q. (Wei), Berry, D. (Diane), Bouchard, L. (Luigi), Das, S. (Shikta), Hakonarson, H. (Hakon), Heikkinen, J. (Jani), Helgeland, Ø. (Øyvind), Hocher, B. (Berthold), Hofman, A. (Albert), Inskip, H.M. (Hazel), Jones, S.E. (Samuel E.), Kogevinas, M. (Manolis), Lind, P.A. (Penelope), Marullo, L. (Letizia), Medland, S.E. (Sarah), Murray, A. (Anna), Murray, J.C. (Jeffrey C.), Njølstad, P.R. (Pa l R.), Nohr, C. (Christian), Reichetzeder, C. (Christoph), Ring, S.M. (Susan), Ruth, K.S. (Katherine S.), Santa-Marina, L. (Loreto), Scholtens, D.M. (Denise M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Tuke, M.A. (Marcus A.), Vaudel, M. (Marc), Weedon, M.N. (Michael), Willemsen, G.A.H.M. (Gonneke), Wood, A.R. (Andrew R.), Yaghootkar, H. (Hanieh), Muglia, L.J. (Louis J.), Bartels, M. (Meike), Relton, C.L. (Caroline), Pennell, C.E. (Craig), Chatzi, L. (Leda), Estivill, X. (Xavier), Holloway, J.W. (John W.), Boomsma, D.I. (Dorret), Montgomery, G.W. (Grant W.), Murabito, J. (Joanne), Spector, T.D. (Timothy), Power, C. (Christine), Järvelin, M.-R. (Marjo-Ritta), Bisgaard, H. (Hans), Grant, S.F.A. (Struan F.A.), Sørensen, T.I.A. (Thorkild I.A.), Jaddoe, V.W. (Vincent W.), Jacobsson, B. (Bo), Melbye, M. (Mads), McCarthy, M.I. (Mark I.), Hattersley, A.T. (Andrew), Hayes, M.G. (M. Geoffrey), Frayling, T.M. (Timothy), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Hyppönen, E. (Elina), Lowe, W.L. (William L.), Evans, D.M. (David M.), Lawlor, D.A. (Debbie A.), Feenstra, B. (Bjarke), Freathy, R.M. (Rachel), Beaumont, R.N. (Robin N.), Warrington, N.M. (Nicole), Cavadino, A. (Alana), Tyrrell, A.W.R., Nodzenski, M. (Michael), Horikoshi, M. (Momoko), Geller, F. (Frank), Myhre, R. (Ronny), Richmond, R.C. (Rebecca C.), Paternoster, L. (Lavinia), Bradfield, J.P. (Jonathan), Kreiner-Møller, E. (Eskil), Huikari, V. (Ville), Metrustry, S. (Sarah), Lunetta, K.L. (Kathryn), Painter, J.N. (Jodie N.), Hottenga, J.J. (Jouke Jan), Allard, C. (Catherine), Barton, S.J. (Sheila), Espinosa, A. (Ana), Marsh, J.A. (Julie), Potter, C. (Catherine), Zhang, G. (Ge), Ang, W.Q. (Wei), Berry, D. (Diane), Bouchard, L. (Luigi), Das, S. (Shikta), Hakonarson, H. (Hakon), Heikkinen, J. (Jani), Helgeland, Ø. (Øyvind), Hocher, B. (Berthold), Hofman, A. (Albert), Inskip, H.M. (Hazel), Jones, S.E. (Samuel E.), Kogevinas, M. (Manolis), Lind, P.A. (Penelope), Marullo, L. (Letizia), Medland, S.E. (Sarah), Murray, A. (Anna), Murray, J.C. (Jeffrey C.), Njølstad, P.R. (Pa l R.), Nohr, C. (Christian), Reichetzeder, C. (Christoph), Ring, S.M. (Susan), Ruth, K.S. (Katherine S.), Santa-Marina, L. (Loreto), Scholtens, D.M. (Denise M.), Sebert, S. (Sylvain), Sengpiel, V. (Verena), Tuke, M.A. (Marcus A.), Vaudel, M. (Marc), Weedon, M.N. (Michael), Willemsen, G.A.H.M. (Gonneke), Wood, A.R. (Andrew R.), Yaghootkar, H. (Hanieh), Muglia, L.J. (Louis J.), Bartels, M. (Meike), Relton, C.L. (Caroline), Pennell, C.E. (Craig), Chatzi, L. (Leda), Estivill, X. (Xavier), Holloway, J.W. (John W.), Boomsma, D.I. (Dorret), Montgomery, G.W. (Grant W.), Murabito, J. (Joanne), Spector, T.D. (Timothy), Power, C. (Christine), Järvelin, M.-R. (Marjo-Ritta), Bisgaard, H. (Hans), Grant, S.F.A. (Struan F.A.), Sørensen, T.I.A. (Thorkild I.A.), Jaddoe, V.W. (Vincent W.), Jacobsson, B. (Bo), Melbye, M. (Mads), McCarthy, M.I. (Mark I.), Hattersley, A.T. (Andrew), Hayes, M.G. (M. Geoffrey), Frayling, T.M. (Timothy), Hivert, M.-F. (Marie-France), Felix, J.F. (Janine), Hyppönen, E. (Elina), Lowe, W.L. (William L.), Evans, D.M. (David M.), Lawlor, D.A. (Debbie A.), Feenstra, B. (Bjarke), and Freathy, R.M. (Rachel)

Abstract

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of Eu

Published
2018
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36. Cohort profile: Pregnancy and childhood epigenetics (PACE) consortium

Author

Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), London, S.J. (Stephanie J.), Felix, J.F. (Janine F.), Joubert, B.R. (Bonnie), Baccarelli, A.A. (Andrea), Sharp, G.C. (Gemma C.), Almqvist, C. (Catarina), Annesi-Maesano, I. (Isabella), Arshad, H. (Hasan), Baïz, N. (Nour), Bakermans-Kranenburg, M.J. (Marian), Bakulski, K.M. (Kelly M.), Binder, E.B. (Elisabeth), Bouchard, L. (Luigi), Breton, C. (Carrie), Brunekreef, B. (Bert), Brunst, K.J. (Kelly J.), Burchard, E.G. (Esteban), Bustamante, M. (Mariona), Chatzi, L. (Leda), Munthe-Kaas, M.C. (Monica Cheng), Corpeleijn, W.E. (Willemijn), Czamara, D. (Darina), Dabelea, D. (Dana), Smith, G.D. (George Davey), Boever, P. (Patrick) de, Duijts, L. (Liesbeth), Dwyer, T. (Terence), Eng, C. (Celeste), Eskenazi, B. (B.), Everson, T.M. (Todd M.), Falahi, F. (Fahimeh), Fallin, M.D. (M. Daniele), Farchi, S. (Sara), Fernandez, M.F. (Mariana), Gao, L. (Lu), Gaunt, T.R. (Tom), Ghantous, A. (Akram), Gillman, M.W. (Matthew W.), Gonseth, S. (Semira), Grote, V. (Veit), Gruzieva, O. (Olena), Håberg, S.E. (Siri E), Herceg, Z. (Zdenko), Hivert, M.-F. (Marie-France), Holland, N. (Nina), Holloway, J.W. (John W.), Hoyo, C. (Cathrine), Hu, D. (Donglei), Huang, R.-C. (Rae-Chi), Huen, K. (Karen), Järvelin, M.-R. (Marjo-Riitta), Jima, D.D. (Dereje D.), Just, A.C. (Allan C.), Karagas, M.R. (Margaret), Karlsson, R. (Robert), Karmaus, W. (Wilfried), Kechris, K.J. (Katerina J.), Kere, J. (Juha), Kogevinas, M. (Manolis), Koletzko, B. (Berthold), Koppelman, G.H. (Gerard), Küpers, A.M. (Marlijn), Ladd-Acosta, C. (Christine), Lahti, J., Lambrechts, N. (Nathalie), Langie, S.A.S. (Sabine A.S.), Lie, R.T. (Rolv T.), Liu, A.H. (Andrew H.), Magnus, M.C. (Maria C.), Magnus, P. (Per), Maguire, R.L. (Rachel L.), Marsit, C.J. (Carmen J.), McArdle, W.L. (Wendy), Melen, E. (Erik), Melton, P. (Phillip), Murphy, S.K. (Susan K.), Nawrot, T.S. (Tim S.), Nisticò, L. (Lorenza), Nohr, C. (Christian), Nordlund, B. (Björn), Nystad, W. (Wenche), Oh, S.S. (Sam S.), Oken, E. (Emily), Page, C.M. (Christian M.), Perron, P. (Patrice), Pershagen, G. (Göran), Pizzi, C. (Costanza), Plusquin, M. (Michelle), Räikkönen, K. (Katri), Reese, S.E. (Sarah E.), Reischl, G. (Gunilla), Richiardi, L. (Lorenzo), Ring, S.M. (Susan), Roy, R.P. (Ritu P.), Rzehak, P. (Peter), Schoeters, G. (Greet), Schwartz, D.A. (David A.), Sebert, S. (Sylvain), Snieder, H. (Harold), Sørensen, T.I.A. (Thorkild), Starling, A.P. (Anne P.), Sunyer, J. (Jordi), Taylor, J.A. (Jack A), Tiemeier, H.W. (Henning), Ullemar, V. (Vilhelmina), Vafeiadi, M. (Marina), IJzendoorn, M.H. (Rien) van, Vonk, J.M. (Judith), Vriens, A. (Annette), Vrijheid, M. (Martine), Wang, P. (Pei), Wiemels, J. (Joseph), Wilcox, A.J. (Allen), Wright, R.J. (Rosalind J.), Xu, C.-J. (Cheng-Jian), Xu, Z. (Zongli), Yang, I.V. (Ivana V.), Yousefi, P. (Paul), Zhang, H. (Hongmei), Zhang, W. (Weiming), Zhao, S. (Shanshan), Agha, G. (Golareh), Relton, C.L. (Caroline), Jaddoe, V.W.V. (Vincent), and London, S.J. (Stephanie J.)

Published
2018
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37. Maternal and fetal genetic contribution to gestational weight gain

Author

Warrington, N.M. (N. M.), Richmond, R.C. (Rebecca C.), Fenstra, B. (B.), Myhre, R. (Ronny), Gaillard, R. (Romy), Paternoster, L. (L.), Wang, C.A. (C. A.), Beaumont, R.N. (R. N.), Das, S. (Shikta), Murcia, M. (Mario), Barton, S.J. (Sheila), Espinosa, A. (A.), Thiering, E. (Elisabeth), Atalay, M. (Mustafa), Pitkanen, N. (Niina), Ntalla, I. (Ioanna), Jonsson, A.E. (A. E.), Freathy, R.M. (Rachel), Karhunen, V. (V.), Tiesler, C.M.T. (C. M.T.), Allard, C. (Catherine), Crawford, A. (A.), Ring, S.M. (Susan), Melbye, M. (Mads), Magnus, P. (Per), Rivadeneira, F. (F.), Skotte, L. (L.), Hansen, T. (Torben), Marsh, J.A. (Julie), Guxens Junyent, M. (Mònica), Holloway, J.W. (J. W.), Grallert, H. (Harald), Jaddoe, V.W.V. (Vincent), Lowe, W.L. (W. L.), Roumeliotaki, T. (Theano), Hattersley, A.T. (Andrew), Lindi, V. (Virpi), Pahkala, K. (Katja), Panoutsopoulou, K. (K.), Standl, M. (M.), Flexeder, C. (Claudia), Bouchard, L. (Luigi), Aagaard Nohr, E. (E.), Santa-Marina, L. (Loreto), Kogevinas, M. (Manolis), Niinikoski, H. (H.), Dedoussis, G.V. (George), Heinrich, J. (J.), Reynolds, R.M. (Rebecca), Lakka, T.A. (Timo), Zeggini, E. (Eleftheria), Raitakari, O.T. (O. T.), Chatzi, L. (Leda), Inskip, H.M. (Hazel), Bustamante, M. (Mariona), Hivert, M.-F. (Marie-France), Jarvelin, M.-R. (M. R.), Sørensen, T.I.A. (Thorkild), Pennell, C.E. (Craig), Felix, J.F. (J. F.), Jacobsson, B. (B.), Geller, F. (Frank), Evans, D.M. (D. M.), Lawlor, D.A. (D. A.), Warrington, N.M. (N. M.), Richmond, R.C. (Rebecca C.), Fenstra, B. (B.), Myhre, R. (Ronny), Gaillard, R. (Romy), Paternoster, L. (L.), Wang, C.A. (C. A.), Beaumont, R.N. (R. N.), Das, S. (Shikta), Murcia, M. (Mario), Barton, S.J. (Sheila), Espinosa, A. (A.), Thiering, E. (Elisabeth), Atalay, M. (Mustafa), Pitkanen, N. (Niina), Ntalla, I. (Ioanna), Jonsson, A.E. (A. E.), Freathy, R.M. (Rachel), Karhunen, V. (V.), Tiesler, C.M.T. (C. M.T.), Allard, C. (Catherine), Crawford, A. (A.), Ring, S.M. (Susan), Melbye, M. (Mads), Magnus, P. (Per), Rivadeneira, F. (F.), Skotte, L. (L.), Hansen, T. (Torben), Marsh, J.A. (Julie), Guxens Junyent, M. (Mònica), Holloway, J.W. (J. W.), Grallert, H. (Harald), Jaddoe, V.W.V. (Vincent), Lowe, W.L. (W. L.), Roumeliotaki, T. (Theano), Hattersley, A.T. (Andrew), Lindi, V. (Virpi), Pahkala, K. (Katja), Panoutsopoulou, K. (K.), Standl, M. (M.), Flexeder, C. (Claudia), Bouchard, L. (Luigi), Aagaard Nohr, E. (E.), Santa-Marina, L. (Loreto), Kogevinas, M. (Manolis), Niinikoski, H. (H.), Dedoussis, G.V. (George), Heinrich, J. (J.), Reynolds, R.M. (Rebecca), Lakka, T.A. (Timo), Zeggini, E. (Eleftheria), Raitakari, O.T. (O. T.), Chatzi, L. (Leda), Inskip, H.M. (Hazel), Bustamante, M. (Mariona), Hivert, M.-F. (Marie-France), Jarvelin, M.-R. (M. R.), Sørensen, T.I.A. (Thorkild), Pennell, C.E. (Craig), Felix, J.F. (J. F.), Jacobsson, B. (B.), Geller, F. (Frank), Evans, D.M. (D. M.), and Lawlor, D.A. (D. A.)

Abstract

Background:Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and methods:A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight).Results:Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10 â '8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG.Conclusions:We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outc

Published
2018
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38. Response to antenatal cholecalciferol supplementation is associated with common vitamin D related genetic variants

Author

Moon, R.J., Harvey, N.C., Cooper, C., D'Angelo, S., Curtis, E.M., Crozier, S.R., Barton, S.J., Robinson, S.M., Godfrey, K.M., Graham, N.J., Holloway, J.W., Bishop, N.J., Kennedy, S., Papageorghiou, A.T., Schoenmakers, I., Fraser, R., Gandhi, S.V., Prentice, A., Inskip, H.M., Javaid, M.K., and MAVIDOS Trial Group, MVT

Abstract

Context: Single nucleotide polymorphisms (SNP) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1 and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization-group analysis of the MAVIDOS trial of antenatal cholecalciferol supplementation. Setting: Hospital antenatal clinics. Participants: 682 women of White ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1) and rs2282679 (GC) were genotyped. Interventions: 1000 IU/day cholecalciferol from 14 weeks gestation until delivery. Main Outcome Measure: 25(OH)D at randomisation and 34 weeks gestation were measured in a single batch (Diasorin Liaison). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model (beta represents the change in 25(OH)D per additional common allele). Results: Only rs12785878 (DHCR7) was associated with baseline 25(OH)D [β=3.1nmol/l (95% CI 1.0, 5.2), p

Published
2017

39. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author

Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)

Abstract

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa

Published
2017
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40. Airway and peripheral urokinase plasminogen activator receptor is elevated in asthma, and identifies a severe, nonatopic subset of patients

Author

Portelli, Michael A., Moseley, C., Stewart, Ceri E., Postma, Dirkje S., Howarth, P., Warner, J.A., Holloway, J.W., Koppelman, Gerard H., and Sayers, Ian

Subjects
biological phenomena, cell phenomena, and immunity, skin and connective tissue diseases, neoplasms, biological factors, respiratory tract diseases
Abstract

Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studieshave identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking. Objectives: We aimed to comprehensively determine the uPAR expression profilein asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features. Methods: uPAR levels were determined in control (n = 9) and asthmatic (n = 27)bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels weredetermined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.Measurements and main results: In bronchial tissue, uPAR was elevated ininflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial(P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-f old; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease. Conclusions: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.

Published
2016

41. EAACI position statement on asthma exacerbations and severe asthma

Author

Custovic, A. Johnston, S.L. Pavord, I. Gaga, M. Fabbri, L. Bel, E.H. Le Souëf, P. Lötvall, J. Demoly, P. Akdis, C.A. Ryan, D. Mäkelä, M.J. Martinez, F. Holloway, J.W. Saglani, S. O'Byrne, P. Papi, A. Sergejeva, S. Magnan, A. Del Giacco, S. Kalayci, O. Hamelmann, E. Papadopoulos, N.G.

Subjects
immune system diseases, respiratory tract diseases
Abstract

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Published
2013

42. Genome-wide association study to identify genetic determinants of severe asthma

Author

Wan, Y.I., Shrine, N.R.G., Soler Artigas, M., Wain, L.V., Blakey, J.D., Moffatt, M.F., Bush, A., Chung, K. F., Cookson, W.O.C.M., Strachan, D.P., Heaney, L., Al-Momani, B.A.H., Mansur, A.H., Manney, S., Thomson, N.C., Chaudhuri, R., Brightling, C.E., Bafadhel, M., Singapuri, A., Niven, R., Simpson, A., Holloway, J.W., Howarth, P.H., Hui, J., Musk, A.W., James, A.L., Brown, M.A., Baltic, S., Ferreira, M.A.R., Thompson, P.J., Tobin, M.D., Sayers, Ian, and Hall, Ian P.

Abstract

Background The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear.Objective To identify common genetic variants affecting susceptibility to severe asthma.Methods A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies.Results An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10(−8) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10(−8) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance.Conclusions The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

Published
2012

43. Common variants at 6q22 and 17q21 are associated with intracranial volume

Author

Ikram, M.A. (Arfan), Fornage, M. (Myriam), Smith, A.V. (Davey), Seshadri, S. (Sudha), Schmidt, R. (Reinhold), Debette, S. (Stéphanie), Vrooman, H.A. (Henri), Sigurdsson, S. (Stefan), Ropele, S. (Stefan), Taal, H.R. (Rob), Mook-Kanamori, D.O. (Dennis), Coker, L.H. (Laura), Longstreth Jr, W.T., Niessen, W.J. (Wiro), DeStefano, A.L. (Anita), Beiser, A. (Alexa), Zijdenbos, A.P., Struchalin, M.V. (Maksim), Jack Jr., C.R. (Clifford), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Knopman, D.S. (David), Hartikainen, A.L., Pennell, C.E. (Craig), Thiering, E. (Eelisabeth), Steegers, E.A.P. (Eric), Hakonarson, H. (Hakon), Heinrich, J. (Joachim), Palmer, C. (Cameron), Jarvelin, M.-R. (Marjo-Riitta), McCarthy, M.I. (Mark), Grant, S.F.A. (Struan), Pourcain, B.S. (Beate), Timpson, N.J. (Nicholas), Sovio, U. (Ulla), Nalls, M.A. (Michael), Au, R. (Rhoda), Hofman, A. (Albert), Gudnason, H. (Haukur), Lugt, A. (Aad) van der, Harris, T.B. (Tamara), Meeks, W.M. (William), Vernooij, M.W. (Meike), Buchem, M.A. (Mark) van, Catellier, D.J. (Diane), Jaddoe, V.W.V. (Vincent), Gudnason, V. (Vilmundur), Windham, B.G. (Gwen), Wolf, P.A. (Philip), Duijn, C.M. (Cornelia) van, Mosley, T.H. (Thomas), Launer, L.J. (Lenore), Breteler, M.M.B. (Monique), DeCarli, C. (Charles), Adair, L.S. (Linda), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N.E. (Nienke), Benke, P.J. (Paul), Berry, D. (Diane), Coin, L. (Lachlan), Davis, O.S.P. (Oliver S.), Elliott, P. (Paul), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Gaillard, R. (Romy), Groen-Blokhuis, M. (Maria), Goh, L.-K., Haworth, C.M.A. (Claire M.), Hadley, D. (David), Hedebrand, J. (Johannes), Hinney, A. (Anke), Hirschhorn, J.N. (Joel), Holloway, J.W. (John), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (Elina), Kilpeläinen, T.O. (Tuomas), Kirin, M. (Mirna), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Lange, L.A. (Leslie), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Lewin, A. (Alex), Lindgren, C.M. (Cecilia), Lindi, V. (Virpi), Maggi, R. (Reedik), Marsh, J.A. (Julie), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Ntalla, I. (Ioanna), Oken, E. (Emily), Panoutsopoulou, K. (Kalliope), Pararajasingham, J. (Jennifer), Rodriguez, A. (Alfredo Chapin), Salem, R.M. (Rany), Sebert, S. (Sylvain), Siitonen, N. (Niina), Strachan, D.P. (David), Teo, Y.Y. (Yik Ying), Valcárcel, B. (Beatriz), Willemsen, G.A.H.M. (Gonneke), Zeggini, E. (Eleftheria), Boomsma, D.I. (Dorret), Cooper, C. (Charles), Gillman, M.H. (Matthew), Hocher, B. (Berthold), Mohlke, K.L. (Karen), Dedoussis, G.V. (George), Ong, K.K. (Ken), Pearson, E. (Ewan), Price, T.S. (Thomas), Power, C. (Christopher), Raitakari, O. (Olli), Saw, S-M. (Seang-Mei), Scherag, A. (Andre), Simell, O. (Olli), Sørensen, T.I.A. (Thorkild), Wilson, J.F. (James), Ikram, M.A. (Arfan), Fornage, M. (Myriam), Smith, A.V. (Davey), Seshadri, S. (Sudha), Schmidt, R. (Reinhold), Debette, S. (Stéphanie), Vrooman, H.A. (Henri), Sigurdsson, S. (Stefan), Ropele, S. (Stefan), Taal, H.R. (Rob), Mook-Kanamori, D.O. (Dennis), Coker, L.H. (Laura), Longstreth Jr, W.T., Niessen, W.J. (Wiro), DeStefano, A.L. (Anita), Beiser, A. (Alexa), Zijdenbos, A.P., Struchalin, M.V. (Maksim), Jack Jr., C.R. (Clifford), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Knopman, D.S. (David), Hartikainen, A.L., Pennell, C.E. (Craig), Thiering, E. (Eelisabeth), Steegers, E.A.P. (Eric), Hakonarson, H. (Hakon), Heinrich, J. (Joachim), Palmer, C. (Cameron), Jarvelin, M.-R. (Marjo-Riitta), McCarthy, M.I. (Mark), Grant, S.F.A. (Struan), Pourcain, B.S. (Beate), Timpson, N.J. (Nicholas), Sovio, U. (Ulla), Nalls, M.A. (Michael), Au, R. (Rhoda), Hofman, A. (Albert), Gudnason, H. (Haukur), Lugt, A. (Aad) van der, Harris, T.B. (Tamara), Meeks, W.M. (William), Vernooij, M.W. (Meike), Buchem, M.A. (Mark) van, Catellier, D.J. (Diane), Jaddoe, V.W.V. (Vincent), Gudnason, V. (Vilmundur), Windham, B.G. (Gwen), Wolf, P.A. (Philip), Duijn, C.M. (Cornelia) van, Mosley, T.H. (Thomas), Launer, L.J. (Lenore), Breteler, M.M.B. (Monique), DeCarli, C. (Charles), Adair, L.S. (Linda), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N.E. (Nienke), Benke, P.J. (Paul), Berry, D. (Diane), Coin, L. (Lachlan), Davis, O.S.P. (Oliver S.), Elliott, P. (Paul), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Gaillard, R. (Romy), Groen-Blokhuis, M. (Maria), Goh, L.-K., Haworth, C.M.A. (Claire M.), Hadley, D. (David), Hedebrand, J. (Johannes), Hinney, A. (Anke), Hirschhorn, J.N. (Joel), Holloway, J.W. (John), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (Elina), Kilpeläinen, T.O. (Tuomas), Kirin, M. (Mirna), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Lange, L.A. (Leslie), Lawlor, D.A. (Debbie), Lehtimäki, T. (Terho), Lewin, A. (Alex), Lindgren, C.M. (Cecilia), Lindi, V. (Virpi), Maggi, R. (Reedik), Marsh, J.A. (Julie), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Ntalla, I. (Ioanna), Oken, E. (Emily), Panoutsopoulou, K. (Kalliope), Pararajasingham, J. (Jennifer), Rodriguez, A. (Alfredo Chapin), Salem, R.M. (Rany), Sebert, S. (Sylvain), Siitonen, N. (Niina), Strachan, D.P. (David), Teo, Y.Y. (Yik Ying), Valcárcel, B. (Beatriz), Willemsen, G.A.H.M. (Gonneke), Zeggini, E. (Eleftheria), Boomsma, D.I. (Dorret), Cooper, C. (Charles), Gillman, M.H. (Matthew), Hocher, B. (Berthold), Mohlke, K.L. (Karen), Dedoussis, G.V. (George), Ong, K.K. (Ken), Pearson, E. (Ewan), Price, T.S. (Thomas), Power, C. (Christopher), Raitakari, O. (Olli), Saw, S-M. (Seang-Mei), Scherag, A. (Andre), Simell, O. (Olli), Sørensen, T.I.A. (Thorkild), and Wilson, J.F. (James)

Abstract

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10 -8) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10 -11), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 10 -12), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 × 10 -3 for 6q22 and 1.2 × 10 -3 for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.

Published
2012
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44. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Author

Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), McCarthy, M.I. (Mark), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), and McCarthy, M.I. (Mark)

Abstract

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102-11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10-8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human

Published
2009
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