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Chan, Lili ; Jaladanki, Suraj K. ; Somani, Sulaiman ; Paranjpe, Ishan ; Kumar, Arvind ; Zhao, Shan ; Kaufman, Lewis ; Leisman, Staci ; Sharma, Shuchita ; He, John Cijiang ; Murphy, Barbara ; Fayad, Zahi A. ; Levin, Matthew A. ; Böttinger, Erwin ; Charney, Alexander W. ; Glicksberg, Benjamin ; Coca, Steven G. ; Nadkarni, Girish N.
Chan, Lili ; Chaudhary, Kumardeep ; Saha, Aparna ; Chauhan, Kinsuk ; Vaid, Akhil ; Zhao, Shan ; Paranjpe, Ishan ; Somani, Sulaiman ; Richter, Felix ; Miotto, Riccardo ; Lala, Anuradha ; Kia, Arash ; Timsina, Prem ; Li, Li ; Freeman, Robert ; Chen, Rong ; Narula, Jagat ; Just, Allan C. ; Horowitz, Carol ; Fayad, Zahi ; Cordon-Cardo, Carlos ; Schadt, Eric ; Levin, Matthew A. ; Reich, David L. ; Fuster, Valentin ; Murphy, Barbara ; He, John C. ; Charney, Alexander W. ; Böttinger, Erwin ; Glicksberg, Benjamin ; Coca, Steven G. ; Nadkarni, Girish N.
Background:
Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associatedwith worse outcomes. However, AKI among hospitalized patients with COVID19 in the United States is not well described.
Methods:
This retrospective, observational study involved a review of data from electronic health records of patients aged >= 18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality.
Results:
Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patientswith AKI required dialysis. The proportionswith stages 1, 2, or 3 AKIwere 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up.
Conclusions:
AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.
Lozano, Yudi M. ; Aguilar-Trigueros, Carlos A. ; Onandia, Gabriela ; Maaß, Stefanie ; Zhao, Tingting ; Rillig, Matthias C.
1. Microplastics in soils have become an important threat for terrestrial systems as they may potentially alter the geochemical/biophysical soil environment and can interact with drought. As microplastics may affect soil water content, this could exacerbate the well-known negative effects of drought on ecosystem functionality. Thus, functions including litter decomposition, soil aggregation or those related with nutrient cycling can be altered. Despite this potential interaction, we know relatively little about how microplastics, under different soil water conditions, affect ecosystem functions and multifunctionality.
2. To address this gap, we performed an experiment using grassland plant communities growing in microcosms. Microplastic fibres (absent, present) and soil water conditions (well-watered, drought) were applied in a fully factorial design. At harvest, we measured soil ecosystem functions related to nutrient cycling (beta-glucosaminidase, beta-D-cellobiosidase, phosphatase, beta-glucosidase enzymes), respiration, nutrient retention, pH, litter decomposition and soil aggregation (water stable aggregates). As terrestrial systems provide these functions simultaneously, we also assessed ecosystem multifunctionality, an index that encompasses the array of ecosystem functions measured here.
3. We found that the interaction between microplastic fibres and drought affected ecosystem functions and multifunctionality. Drought had negatively affected nutrient cycling by decreasing enzymatic activities by up to similar to 39%, while microplastics increased soil aggregation by similar to 18%, soil pH by similar to 4% and nutrient retention by up to similar to 70% by diminishing nutrient leaching. Microplastic fibres also impacted soil enzymes, respiration and ecosystem multifunctionality, but importantly, the direction of these effects depended on soil water status. That is, under well-watered conditions, these functions decreased with microplastic fibres by up to similar to 34% while under drought they had similar values irrespective of the microplastic presence, or tended to increase with microplastics. Litter decomposition had a contrary pattern increasing with microplastics by similar to 6% under well-watered conditions while decreasing to a similar percentage under drought.
4. Synthesis and applications. Single ecosystem functions can be positively or negatively affected by microplastics fibres depending on soil water status. However, our results suggest that microplastic fibres may cause negative effects on ecosystem soil multifunctionality of a similar magnitude as drought. Thus, strategies to counteract this new global change factor are necessary.
Vaid, Akhil ; Somani, Sulaiman ; Russak, Adam J. ; De Freitas, Jessica K. ; Chaudhry, Fayzan F. ; Paranjpe, Ishan ; Johnson, Kipp W. ; Lee, Samuel J. ; Miotto, Riccardo ; Richter, Felix ; Zhao, Shan ; Beckmann, Noam D. ; Naik, Nidhi ; Kia, Arash ; Timsina, Prem ; Lala, Anuradha ; Paranjpe, Manish ; Golden, Eddye ; Danieletto, Matteo ; Singh, Manbir ; Meyer, Dara ; O'Reilly, Paul F. ; Huckins, Laura ; Kovatch, Patricia ; Finkelstein, Joseph ; Freeman, Robert M. ; Argulian, Edgar ; Kasarskis, Andrew ; Percha, Bethany ; Aberg, Judith A. ; Bagiella, Emilia ; Horowitz, Carol R. ; Murphy, Barbara ; Nestler, Eric J. ; Schadt, Eric E. ; Cho, Judy H. ; Cordon-Cardo, Carlos ; Fuster, Valentin ; Charney, Dennis S. ; Reich, David L. ; Böttinger, Erwin ; Levin, Matthew A. ; Narula, Jagat ; Fayad, Zahi A. ; Just, Allan C. ; Charney, Alexander W. ; Nadkarni, Girish N. ; Glicksberg, Benjamin S.
Background:
COVID-19 has infected millions of people worldwide and is responsible for several hundred thousand fatalities. The COVID-19 pandemic has necessitated thoughtful resource allocation and early identification of high-risk patients. However, effective methods to meet these needs are lacking.
Objective:
The aims of this study were to analyze the electronic health records (EHRs) of patients who tested positive for COVID-19 and were admitted to hospitals in the Mount Sinai Health System in New York City; to develop machine learning models for making predictions about the hospital course of the patients over clinically meaningful time horizons based on patient characteristics at admission; and to assess the performance of these models at multiple hospitals and time points.
Methods:
We used Extreme Gradient Boosting (XGBoost) and baseline comparator models to predict in-hospital mortality and critical events at time windows of 3, 5, 7, and 10 days from admission. Our study population included harmonized EHR data from five hospitals in New York City for 4098 COVID-19-positive patients admitted from March 15 to May 22, 2020. The models were first trained on patients from a single hospital (n=1514) before or on May 1, externally validated on patients from four other hospitals (n=2201) before or on May 1, and prospectively validated on all patients after May 1 (n=383). Finally, we established model interpretability to identify and rank variables that drive model predictions.
Results:
Upon cross-validation, the XGBoost classifier outperformed baseline models, with an area under the receiver operating characteristic curve (AUC-ROC) for mortality of 0.89 at 3 days, 0.85 at 5 and 7 days, and 0.84 at 10 days. XGBoost also performed well for critical event prediction, with an AUC-ROC of 0.80 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. In external validation, XGBoost achieved an AUC-ROC of 0.88 at 3 days, 0.86 at 5 days, 0.86 at 7 days, and 0.84 at 10 days for mortality prediction. Similarly, the unimputed XGBoost model achieved an AUC-ROC of 0.78 at 3 days, 0.79 at 5 days, 0.80 at 7 days, and 0.81 at 10 days. Trends in performance on prospective validation sets were similar. At 7 days, acute kidney injury on admission, elevated LDH, tachypnea, and hyperglycemia were the strongest drivers of critical event prediction, while higher age, anion gap, and C-reactive protein were the strongest drivers of mortality prediction.
Conclusions:
We externally and prospectively trained and validated machine learning models for mortality and critical events for patients with COVID-19 at different time horizons. These models identified at-risk patients and uncovered underlying relationships that predicted outcomes.
Warrington, Nicole ; Beaumont, Robin ; Horikoshi, Momoko ; Day, Felix R. ; Helgeland, Øyvind ; Laurin, Charles ; Bacelis, Jonas ; Peng, Shouneng ; Hao, Ke ; Feenstra, Bjarke ; Wood, Andrew R. ; Mahajan, Anubha ; Tyrrell, Jessica ; Robertson, Neil R. ; Rayner, N. William ; Qiao, Zhen ; Moen, Gunn-Helen ; Vaudel, Marc ; Marsit, Carmen ; Chen, Jia ; Nodzenski, Michael ; Schnurr, Theresia M. ; Zafarmand, Mohammad Hadi ; Bradfield, Jonathan P. ; Grarup, Niels ; Kooijman, Marjolein N. ; Li-Gao, Ruifang ; Geller, Frank ; Ahluwalia, Tarunveer Singh ; Paternoster, Lavinia ; Rueedi, Rico ; Huikari, Ville ; Hottenga, Jouke-Jan ; Lyytikäinen, Leo-Pekka ; Cavadino, Alana ; Metrustry, Sarah ; Cousminer, Diana L. ; Wu, Ying ; Thiering, Elisabeth Paula ; Wang, Carol A. ; Have, Christian Theil ; Vilor-Tejedor, Natalia ; Joshi, Peter K. ; Painter, Jodie N. ; Ntalla, Ioanna ; Myhre, Ronny ; Pitkänen, Niina ; van Leeuwen, Elisabeth M. ; Joro, Raimo ; Lagou, Vasiliki ; Richmond, Rebecca C. ; Espinosa, Ana ; Barton, Sheila J. ; Inskip, Hazel M. ; Holloway, John W. ; Santa-Marina, Loreto ; Estivill, Xavier ; Ang, Wei ; Marsh, Julie A. ; Reichetzeder, Christoph ; Marullo, Letizia ; Hocher, Berthold ; Lunetta, Kathryn L. ; Murabito, Joanne M. ; Relton, Caroline L. ; Kogevinas, Manolis ; Chatzi, Leda ; Allard, Catherine ; Bouchard, Luigi ; Hivert, Marie-France ; Zhang, Ge ; Muglia, Louis J. ; Heikkinen, Jani ; Morgen, Camilla S. ; van Kampen, Antoine H. C. ; van Schaik, Barbera D. C. ; Mentch, Frank D. ; Langenberg, Claudia ; Scott, Robert A. ; Zhao, Jing Hua ; Hemani, Gibran ; Ring, Susan M. ; Bennett, Amanda J. ; Gaulton, Kyle J. ; Fernandez-Tajes, Juan ; van Zuydam, Natalie R. ; Medina-Gomez, Carolina ; de Haan, Hugoline G. ; Rosendaal, Frits R. ; Kutalik, Zoltán ; Marques-Vidal, Pedro ; Das, Shikta ; Willemsen, Gonneke ; Mbarek, Hamdi ; Müller-Nurasyid, Martina ; Standl, Marie ; Appel, Emil V. R. ; Fonvig, Cilius Esmann ; Trier, Caecilie ; van Beijsterveldt, Catharina E. M. ; Murcia, Mario ; Bustamante, Mariona ; Bonàs-Guarch, Sílvia ; Hougaard, David M. ; Mercader, Josep M. ; Linneberg, Allan ; Schraut, Katharina E. ; Lind, Penelope A. ; Medland, Sarah Elizabeth ; Shields, Beverley M. ; Knight, Bridget A. ; Chai, Jin-Fang ; Panoutsopoulou, Kalliope ; Bartels, Meike ; Sánchez, Friman ; Stokholm, Jakob ; Torrents, David ; Vinding, Rebecca K. ; Willems, Sara M. ; Atalay, Mustafa ; Chawes, Bo L. ; Kovacs, Peter ; Prokopenko, Inga ; Tuke, Marcus A. ; Yaghootkar, Hanieh ; Ruth, Katherine S. ; Jones, Samuel E. ; Loh, Po-Ru ; Murray, Anna ; Weedon, Michael N. ; Tönjes, Anke ; Stumvoll, Michael ; Michaelsen, Kim Fleischer ; Eloranta, Aino-Maija ; Lakka, Timo A. ; van Duijn, Cornelia M. ; Kiess, Wieland ; Koerner, Antje ; Niinikoski, Harri ; Pahkala, Katja ; Raitakari, Olli T. ; Jacobsson, Bo ; Zeggini, Eleftheria ; Dedoussis, George V. ; Teo, Yik-Ying ; Saw, Seang-Mei ; Montgomery, Grant W. ; Campbell, Harry ; Wilson, James F. ; Vrijkotte, Tanja G. M. ; Vrijheid, Martine ; de Geus, Eco J. C. N. ; Hayes, M. Geoffrey ; Kadarmideen, Haja N. ; Holm, Jens-Christian ; Beilin, Lawrence J. ; Pennell, Craig E. ; Heinrich, Joachim ; Adair, Linda S. ; Borja, Judith B. ; Mohlke, Karen L. ; Eriksson, Johan G. ; Widen, Elisabeth E. ; Hattersley, Andrew T. ; Spector, Tim D. ; Kaehoenen, Mika ; Viikari, Jorma S. ; Lehtimaeki, Terho ; Boomsma, Dorret I. ; Sebert, Sylvain ; Vollenweider, Peter ; Sorensen, Thorkild I. A. ; Bisgaard, Hans ; Bonnelykke, Klaus ; Murray, Jeffrey C. ; Melbye, Mads ; Nohr, Ellen A. ; Mook-Kanamori, Dennis O. ; Rivadeneira, Fernando ; Hofman, Albert ; Felix, Janine F. ; Jaddoe, Vincent W. V. ; Hansen, Torben ; Pisinger, Charlotta ; Vaag, Allan A. ; Pedersen, Oluf ; Uitterlinden, Andre G. ; Jarvelin, Marjo-Riitta ; Power, Christine ; Hypponen, Elina ; Scholtens, Denise M. ; Lowe, William L. ; Smith, George Davey ; Timpson, Nicholas J. ; Morris, Andrew P. ; Wareham, Nicholas J. ; Hakonarson, Hakon ; Grant, Struan F. A. ; Frayling, Timothy M. ; Lawlor, Debbie A. ; Njolstad, Pal R. ; Johansson, Stefan ; Ong, Ken K. ; McCarthy, Mark I. ; Perry, John R. B. ; Evans, David M. ; Freathy, Rachel M.
Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Rothe, Martin ; Zhao, Yuhang ; Kewes, Günter ; Kochovski, Zdravko ; Sigle, Wilfried ; van Aken, Peter A. ; Koch, Christoph ; Ballauff, Matthias ; Lu, Yan ; Benson, Oliver
Metal nanoparticles are the most frequently used nanostructures in plasmonics. However, besides nanoparticles, metal nanowires feature several advantages for applications. Their elongation offers a larger interaction volume, their resonances can reach higher quality factors, and their mode structure provides better coupling into integrated hybrid dielectric-plasmonic circuits. It is crucial though, to control the distance of the wire to a supporting substrate, to another metal layer or to active materials with sub-nanometer precision. A dielectric coating can be utilized for distance control, but it must not degrade the plasmonic properties. In this paper, we introduce a controlled synthesis and coating approach for silver nanowires to fulfill these demands. We synthesize and characterize silver nanowires of around 70 nm in diameter. These nanowires are coated with nm-sized silica shells using a modified Stober method to achieve a homogeneous and smooth surface quality. We use transmission electron microscopy, dark-field microscopy and electron-energy loss spectroscopy to study morphology and plasmonic resonances of individual nanowires and quantify the influence of the silica coating. Thorough numerical simulations support the experimental findings showing that the coating does not deteriorate the plasmonic properties and thus introduce silver nanowires as usable building blocks for integrated hybrid plasmonic systems.
Khider, D. ; Emile-Geay, J. ; McKay, N. P. ; Gil, Y. ; Garijo, D. ; Ratnakar, V ; Alonso-Garcia, M. ; Bertrand, S. ; Bothe, O. ; Brewer, P. ; Bunn, A. ; Chevalier, M. ; Comas-Bru, L. ; Csank, A. ; Dassie, E. ; DeLong, K. ; Felis, T. ; Francus, P. ; Frappier, A. ; Gray, W. ; Goring, S. ; Jonkers, L. ; Kahle, M. ; Kaufman, D. ; Kehrwald, N. M. ; Martrat, B. ; McGregor, H. ; Richey, J. ; Schmittner, A. ; Scroxton, N. ; Sutherland, E. ; Thirumalai, Kaustubh ; Allen, K. ; Arnaud, F. ; Axford, Y. ; Barrows, T. ; Bazin, L. ; Birch, S. E. Pilaar ; Bradley, E. ; Bregy, J. ; Capron, E. ; Cartapanis, O. ; Chiang, H-W ; Cobb, K. M. ; Debret, M. ; Dommain, Réne ; Du, J. ; Dyez, K. ; Emerick, S. ; Erb, M. P. ; Falster, G. ; Finsinger, W. ; Fortier, D. ; Gauthier, Nicolas ; George, S. ; Grimm, E. ; Hertzberg, J. ; Hibbert, F. ; Hillman, A. ; Hobbs, W. ; Huber, M. ; Hughes, A. L. C. ; Jaccard, S. ; Ruan, J. ; Kienast, M. ; Konecky, B. ; Le Roux, G. ; Lyubchich, V ; Novello, V. F. ; Olaka, L. ; Partin, J. W. ; Pearce, C. ; Phipps, S. J. ; Pignol, C. ; Piotrowska, N. ; Poli, M-S ; Prokopenko, A. ; Schwanck, F. ; Stepanek, C. ; Swann, G. E. A. ; Telford, R. ; Thomas, E. ; Thomas, Z. ; Truebe, S. ; von Gunten, L. ; Waite, A. ; Weitzel, N. ; Wilhelm, B. ; Williams, J. ; Winstrup, M. ; Zhao, N. ; Zhou, Y.
The progress of science is tied to the standardization of measurements, instruments, and data. This is especially true in the Big Data age, where analyzing large data volumes critically hinges on the data being standardized. Accordingly, the lack of community-sanctioned data standards in paleoclimatology has largely precluded the benefits of Big Data advances in the field. Building upon recent efforts to standardize the format and terminology of paleoclimate data, this article describes the Paleoclimate Community reporTing Standard (PaCTS), a crowdsourced reporting standard for such data. PaCTS captures which information should be included when reporting paleoclimate data, with the goal of maximizing the reuse value of paleoclimate data sets, particularly for synthesis work and comparison to climate model simulations. Initiated by the LinkedEarth project, the process to elicit a reporting standard involved an international workshop in 2016, various forms of digital community engagement over the next few years, and grassroots working groups. Participants in this process identified important properties across paleoclimate archives, in addition to the reporting of uncertainties and chronologies; they also identified archive-specific properties and distinguished reporting standards for new versus legacy data sets. This work shows that at least 135 respondents overwhelmingly support a drastic increase in the amount of metadata accompanying paleoclimate data sets. Since such goals are at odds with present practices, we discuss a transparent path toward implementing or revising these recommendations in the near future, using both bottom-up and top-down approaches.
Tomographic Reservoir Imaging with DNA-Labeled Silica Nanotracers: The First Field Validation
(2018)
Kong, Xiang-Zhao ; Deuber, Claudia A. ; Kittilä, Anniina ; Somogyvári, Márk ; Mikutis, Gediminas ; Bayer, Peter ; Stark, Wendelin J. ; Saar, Martin O.
This study presents the first field validation of using DNA-labeled silica nanoparticles as tracers to image subsurface reservoirs by travel time based tomography. During a field campaign in Switzerland, we performed short-pulse tracer tests under a forced hydraulic head gradient to conduct a multisource-multireceiver tracer test and tomographic inversion, determining the two-dimensional hydraulic conductivity field between two vertical wells. Together with three traditional solute dye tracers, we injected spherical silica nanotracers, encoded with synthetic DNA molecules, which are protected by a silica layer against damage due to chemicals, microorganisms, and enzymes. Temporal moment analyses of the recorded tracer concentration breakthrough curves (BTCs) indicate higher mass recovery, less mean residence time, and smaller dispersion of the DNA-labeled nanotracers, compared to solute dye tracers. Importantly, travel time based tomography, using nanotracer BTCs, yields a satisfactory hydraulic conductivity tomogram, validated by the dye tracer results and previous field investigations. These advantages of DNA-labeled nanotracers, in comparison to traditional solute dye tracers, make them well-suited for tomographic reservoir characterizations in fields such as hydrogeology, petroleum engineering, and geothermal energy, particularly with respect to resolving preferential flow paths or the heterogeneity of contact surfaces or by enabling source zone characterizations of dense nonaqueous phase liquids.
Licht, Alexis ; Dupont-Nivet, Guillaume ; Pullen, Alex ; Kapp, Paul ; Abels, Hemmo A. ; Lai, Zulong ; Guo, ZhaoJie ; Abell, Jordan ; Giesler, Dominique
The onset of modern central Asian atmospheric circulation is traditionally linked to the interplay of surface uplift of the Mongolian and Tibetan-Himalayan orogens, retreat of the Paratethys sea from central Asia and Cenozoic global cooling. Although the role of these players has not yet been unravelled, the vast dust deposits of central China support the presence of arid conditions and modern atmospheric pathways for the last 25 million years (Myr). Here, we present provenance data from older (42-33 Myr) dust deposits, at a time when the Tibetan Plateau was less developed, the Paratethys sea still present in central Asia and atmospheric pCO(2) much higher. Our results show that dust sources and near-surface atmospheric circulation have changed little since at least 42 Myr. Our findings indicate that the locus of central Asian high pressures and concurrent aridity is a resilient feature only modulated by mountain building, global cooling and sea retreat.
Horikoshi, Momoko ; Yaghootkar, Hanieh ; Mook-Kanamori, Dennis O. ; Sovio, Ulla ; Taal, H. Rob ; Hennig, Branwen J. ; Bradfield, Jonathan P. ; St Pourcain, Beate ; Evans, David M. ; Charoen, Pimphen ; Kaakinen, Marika ; Cousminer, Diana L. ; Lehtimaki, Terho ; Kreiner-Moller, Eskil ; Warrington, Nicole M. ; Bustamante, Mariona ; Feenstra, Bjarke ; Berry, Diane J. ; Thiering, Elisabeth ; Pfab, Thiemo ; Barton, Sheila J. ; Shields, Beverley M. ; Kerkhof, Marjan ; van Leeuwen, Elisabeth M. ; Fulford, Anthony J. ; Kutalik, Zoltan ; Zhao, Jing Hua ; den Hoed, Marcel ; Mahajan, Anubha ; Lindi, Virpi ; Goh, Liang-Kee ; Hottenga, Jouke-Jan ; Wu, Ying ; Raitakari, Olli T. ; Harder, Marie N. ; Meirhaeghe, Aline ; Ntalla, Ioanna ; Salem, Rany M. ; Jameson, Karen A. ; Zhou, Kaixin ; Monies, Dorota M. ; Lagou, Vasiliki ; Kirin, Mirna ; Heikkinen, Jani ; Adair, Linda S. ; Alkuraya, Fowzan S. ; Al-Odaib, Ali ; Amouyel, Philippe ; Andersson, Ehm Astrid ; Bennett, Amanda J. ; Blakemore, Alexandra I. F. ; Buxton, Jessica L. ; Dallongeville, Jean ; Das, Shikta ; de Geus, Eco J. C. ; Estivill, Xavier ; Flexeder, Claudia ; Froguel, Philippe ; Geller, Frank ; Godfrey, Keith M. ; Gottrand, Frederic ; Groves, Christopher J. ; Hansen, Torben ; Hirschhorn, Joel N. ; Hofman, Albert ; Hollegaard, Mads V. ; Hougaard, David M. ; Hyppoenen, Elina ; Inskip, Hazel M. ; Isaacs, Aaron ; Jorgensen, Torben ; Kanaka-Gantenbein, Christina ; Kemp, John P. ; Kiess, Wieland ; Kilpelainen, Tuomas O. ; Klopp, Norman ; Knight, Bridget A. ; Kuzawa, Christopher W. ; McMahon, George ; Newnham, John P. ; Niinikoski, Harri ; Oostra, Ben A. ; Pedersen, Louise ; Postma, Dirkje S. ; Ring, Susan M. ; Rivadeneira, Fernando ; Robertson, Neil R. ; Sebert, Sylvain ; Simell, Olli ; Slowinski, Torsten ; Tiesler, Carla M. T. ; Toenjes, Anke ; Vaag, Allan ; Viikari, Jorma S. ; Vink, Jacqueline M. ; Vissing, Nadja Hawwa ; Wareham, Nicholas J. ; Willemsen, Gonneke ; Witte, Daniel R. ; Zhang, Haitao ; Zhao, Jianhua ; Wilson, James F. ; Stumvoll, Michael ; Prentice, Andrew M. ; Meyer, Brian F. ; Pearson, Ewan R. ; Boreham, Colin A. G. ; Cooper, Cyrus ; Gillman, Matthew W. ; Dedoussis, George V. ; Moreno, Luis A. ; Pedersen, Oluf ; Saarinen, Maiju ; Mohlke, Karen L. ; Boomsma, Dorret I. ; Saw, Seang-Mei ; Lakka, Timo A. ; Koerner, Antje ; Loos, Ruth J. F. ; Ong, Ken K. ; Vollenweider, Peter ; van Duijn, Cornelia M. ; Koppelman, Gerard H. ; Hattersley, Andrew T. ; Holloway, John W. ; Hocher, Berthold ; Heinrich, Joachim ; Power, Chris ; Melbye, Mads ; Guxens, Monica ; Pennell, Craig E. ; Bonnelykke, Klaus ; Bisgaard, Hans ; Eriksson, Johan G. ; Widen, Elisabeth ; Hakonarson, Hakon ; Uitterlinden, Andre G. ; Pouta, Anneli ; Lawlor, Debbie A. ; Smith, George Davey ; Frayling, Timothy M. ; McCarthy, Mark I. ; Grant, Struan F. A. ; Jaddoe, Vincent W. V. ; Jarvelin, Marjo-Riitta ; Timpson, Nicholas J. ; Prokopenko, Inga ; Freathy, Rachel M.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.