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1. The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses

Author

Faber, Benjamin G, Frysz, Monika, Boer, Cindy G, Evans, Daniel S, Ebsim, Raja, Flynn, Kaitlyn A, Lundberg, Mischa, Southam, Lorraine, Hartley, April, Saunders, Fiona R, Lindner, Claudia, Gregory, Jennifer S, Aspden, Richard M, Lane, Nancy E, Harvey, Nicholas C, Evans, David M, Zeggini, Eleftheria, Davey Smith, George, Cootes, Timothy, Van Meurs, Joyce, Kemp, John P, and Tobias, Jonathan H

Subjects
Arthritis, Clinical Research, Genetics, Aging, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Musculoskeletal, Cartilage, Genome-wide association study, Mendelian randomisation, Osteoarthritis, Clinical Sciences, Public Health and Health Services, Clinical sciences, Epidemiology
Abstract

BackgroundHip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest.MethodsGWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA.Findings50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (ORIVW 0.98 [95% CI 0.82-1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life.InterpretationsOne group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism.FundingPrimarily funded by the Medical Research Council and Wellcome Trust.

Published
2023

2. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author

Cuellar-Partida, Gabriel, Tung, Joyce Y, Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A, Barroso, Inês, Beckmann, Jacques S, Boks, Marco P, Boomsma, Dorret I, Boyd, Heather A, Breteler, Monique MB, Campbell, Harry, Chasman, Daniel I, Cherkas, Lynn F, Davies, Gail, de Geus, Eco JC, Deary, Ian J, Deloukas, Panos, Dick, Danielle M, Duffy, David L, Eriksson, Johan G, Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D, Han, Jiali, Hansen, Thomas F, Hartmann, Annette M, Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A, Hirschhorn, Joel N, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Liang-Dar, Ikram, M Arfan, Kaprio, Jaakko, Kemp, John P, Khaw, Kay-Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth JF, Luciano, Michelle, Magnusson, Sigurdur H, Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G, McArdle, Wendy L, McCarthy, Mark I, Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A, Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R, O’Connell, Kevin S, Ophoff, Roel A, Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda WJH, Polasek, Ozren, Pramstaller, Peter P, Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H, Smith, George Davey, Smoller, Jordan W, Soranzo, Nicole, Spector, Tim D, Pourcain, Beate St, Starr, John M, Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J, Uitterlinden, André G, van Duijn, Cornelia M, van Rooij, Frank JA, Vink, Jaqueline M, Vollenweider, Peter, Vuoksimaa, Eero, and Waeber, Gérard

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Human Genome, Mental Health, Brain Disorders, Neurosciences, Schizophrenia, Genetics, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adult, Aged, Female, Functional Laterality, Gene Frequency, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Sex Factors, Biomedical and clinical sciences, Health sciences
Abstract

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P

Published
2021

3. The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis: findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses

Author

Faber, Benjamin G., Frysz, Monika, Boer, Cindy G., Evans, Daniel S., Ebsim, Raja, Flynn, Kaitlyn A., Lundberg, Mischa, Southam, Lorraine, Hartley, April, Saunders, Fiona R., Lindner, Claudia, Gregory, Jennifer S., Aspden, Richard M., Lane, Nancy E., Harvey, Nicholas C., Evans, David M., Zeggini, Eleftheria, Davey Smith, George, Cootes, Timothy, Van Meurs, Joyce, Kemp, John P., and Tobias, Jonathan H.

Published
2023
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5. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author

Ligthart, Symen, Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G, de Vries, Paul S, Prins, Bram P, Van der Most, Peter J, Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M, Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P, Abbasi, Ali, Kacprowski, Tim, Verweij, Niek, Smith, Albert V, Huang, Tao, Marzi, Carola, Feitosa, Mary F, Lohman, Kurt K, Kleber, Marcus E, Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Perola, Markus, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E, Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian’an, Bak, Tom, Schork, Nicholas, Del Greco M., Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E, Mihailov, Evelin, Eriksson, Johan, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B, Schurmann, Claudia, Hollander, Wouter den, Ahluwalia, Tarunveer Singh, Zhao, Jing, Draisma, Harmen HM, Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K, Yanek, Lisa R, Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O’Connell, Jeff R, Laakso, Markku, Giulianini, Franco, Magnusson, Patrik KE, Ballantyne, Christie M, and Hottenga, Jouke Jan

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Mental Illness, Prevention, Mental Health, 2.1 Biological and endogenous factors, Inflammatory and immune system, Generic health relevance, Mental health, Good Health and Well Being, Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Bipolar Disorder, Body Mass Index, C-Reactive Protein, Child, Female, Genetic Loci, Genome-Wide Association Study, Humans, Inflammation, Liver, Male, Mendelian Randomization Analysis, Metabolic Networks and Pathways, Middle Aged, Schizophrenia, Young Adult, LifeLines Cohort Study, CHARGE Inflammation Working Group, C-reactive protein, DEPICT, Mendelian randomization, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, schizophrenia, system biology, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

Published
2018

6. Limb development genes underlie variation in human fingerprint patterns

Author

Li, Jinxi, Glover, James D., Zhang, Haiguo, Peng, Meifang, Tan, Jingze, Mallick, Chandana Basu, Hou, Dan, Yang, Yajun, Wu, Sijie, Liu, Yu, Peng, Qianqian, Zheng, Shijie C., Crosse, Edie I., Medvinsky, Alexander, Anderson, Richard A., Brown, Helen, Yuan, Ziyu, Zhou, Shen, Xu, Yanqing, Kemp, John P., Ho, Yvonne Y.W., Loesch, Danuta Z., Wang, Lizhong, Li, Yingxiang, Tang, Senwei, Wu, Xiaoli, Walters, Robin G., Lin, Kuang, Meng, Ruogu, Lv, Jun, Chernus, Jonathan M., Neiswanger, Katherine, Feingold, Eleanor, Evans, David M., Medland, Sarah E., Martin, Nicholas G., Weinberg, Seth M., Marazita, Mary L., Chen, Gang, Chen, Zhengming, Zhou, Yong, Cheeseman, Michael, Wang, Lan, Jin, Li, Headon, Denis J., and Wang, Sijia

Published
2022
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9. Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects

Author

Medina-Gomez, Carolina, Kemp, John P, Trajanoska, Katerina, Luan, Jian’an, Chesi, Alessandra, Ahluwalia, Tarunveer S, Mook-Kanamori, Dennis O, Ham, Annelies, Hartwig, Fernando P, Evans, Daniel S, Joro, Raimo, Nedeljkovic, Ivana, Zheng, Hou-Feng, Zhu, Kun, Atalay, Mustafa, Liu, Ching-Ti, Nethander, Maria, Broer, Linda, Porleifsson, Gudmar, Mullin, Benjamin H, Handelman, Samuel K, Nalls, Mike A, Jessen, Leon E, Heppe, Denise HM, Richards, J Brent, Wang, Carol, Chawes, Bo, Schraut, Katharina E, Amin, Najaf, Wareham, Nick, Karasik, David, Van der Velde, Nathalie, Ikram, M Arfan, Zemel, Babette S, Zhou, Yanhua, Carlsson, Christian J, Liu, Yongmei, McGuigan, Fiona E, Boer, Cindy G, Bønnelykke, Klaus, Ralston, Stuart H, Robbins, John A, Walsh, John P, Zillikens, M Carola, Langenberg, Claudia, Li-Gao, Ruifang, Williams, Frances MK, Harris, Tamara B, Akesson, Kristina, Jackson, Rebecca D, Sigurdsson, Gunnar, Heijer, Martin den, van der Eerden, Bram CJ, van de Peppel, Jeroen, Spector, Timothy D, Pennell, Craig, Horta, Bernardo L, Felix, Janine F, Zhao, Jing Hua, Wilson, Scott G, de Mutsert, Renée, Bisgaard, Hans, Styrkársdóttir, Unnur, Jaddoe, Vincent W, Orwoll, Eric, Lakka, Timo A, Scott, Robert, Grant, Struan FA, Lorentzon, Mattias, van Duijn, Cornelia M, Wilson, James F, Stefansson, Kari, Psaty, Bruce M, Kiel, Douglas P, Ohlsson, Claes, Ntzani, Evangelia, van Wijnen, Andre J, Forgetta, Vincenzo, Ghanbari, Mohsen, Logan, John G, Williams, Graham R, Bassett, JH Duncan, Croucher, Peter I, Evangelou, Evangelos, Uitterlinden, Andre G, Ackert-Bicknell, Cheryl L, Tobias, Jonathan H, Evans, David M, and Rivadeneira, Fernando

Subjects
Rare Diseases, Aging, Human Genome, Osteoporosis, Clinical Research, Genetics, Aetiology, 2.1 Biological and endogenous factors, Musculoskeletal, Good Health and Well Being, Adolescent, Age Factors, Animals, Bone Density, Child, Child, Preschool, Genetic Loci, Genome-Wide Association Study, Humans, Infant, Infant, Newborn, Mice, Knockout, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Regression Analysis, BMD, CREB3L1, ESR1, GWASs, RANKL, age-dependent effects, bone mineral density, fracture, genetic correlation, genome-wide association studies, meta-regression, total-body DXA, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Bone mineral density (BMD) assessed by DXA is used to evaluate bone health. In children, total body (TB) measurements are commonly used; in older individuals, BMD at the lumbar spine (LS) and femoral neck (FN) is used to diagnose osteoporosis. To date, genetic variants in more than 60 loci have been identified as associated with BMD. To investigate the genetic determinants of TB-BMD variation along the life course and test for age-specific effects, we performed a meta-analysis of 30 genome-wide association studies (GWASs) of TB-BMD including 66,628 individuals overall and divided across five age strata, each spanning 15 years. We identified variants associated with TB-BMD at 80 loci, of which 36 have not been previously identified; overall, they explain approximately 10% of the TB-BMD variance when combining all age groups and influence the risk of fracture. Pathway and enrichment analysis of the association signals showed clustering within gene sets implicated in the regulation of cell growth and SMAD proteins, overexpressed in the musculoskeletal system, and enriched in enhancer and promoter regions. These findings reveal TB-BMD as a relevant trait for genetic studies of osteoporosis, enabling the identification of variants and pathways influencing different bone compartments. Only variants in ESR1 and close proximity to RANKL showed a clear effect dependency on age. This most likely indicates that the majority of genetic variants identified influence BMD early in life and that their effect can be captured throughout the life course.

Published
2018

10. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

Author

McDonald, Michelle M., Khoo, Weng Hua, Ng, Pei Ying, Xiao, Ya, Zamerli, Jad, Thatcher, Peter, Kyaw, Wunna, Pathmanandavel, Karrnan, Grootveld, Abigail K., Moran, Imogen, Butt, Danyal, Nguyen, Akira, Corr, Alexander, Warren, Sean, Biro, Maté, Butterfield, Natalie C., Guilfoyle, Siobhan E., Komla-Ebri, Davide, Dack, Michael R.G., Dewhurst, Hannah F., Logan, John G., Li, Yongxiao, Mohanty, Sindhu T., Byrne, Niall, Terry, Rachael L., Simic, Marija K., Chai, Ryan, Quinn, Julian M.W., Youlten, Scott E., Pettitt, Jessica A., Abi-Hanna, David, Jain, Rohit, Weninger, Wolfgang, Lundberg, Mischa, Sun, Shuting, Ebetino, Frank H., Timpson, Paul, Lee, Woei Ming, Baldock, Paul A., Rogers, Michael J., Brink, Robert, Williams, Graham R., Bassett, J.H. Duncan, Kemp, John P., Pavlos, Nathan J., Croucher, Peter I., and Phan, Tri Giang

Published
2021
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11. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Author

van den Berg, Stéphanie M, de Moor, Marleen HM, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Arias Vasquez, Alejandro, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abdellaoui, Abdel, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Smith, George Davey, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Mbarek, Hamdi, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Nivard, Michel G, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Generation Scotland, Porteous, David, Minelli, Alessandra, and Palmer, Abraham A

Subjects
Biological Psychology, Epidemiology, Health Sciences, Psychology, Human Genome, Genetics, Prevention, 2.1 Biological and endogenous factors, Generic health relevance, Cohort Studies, Extraversion, Psychological, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Personality, Polymorphism, Single Nucleotide, Risk Factors, Generation Scotland, Common genetic variants, Imputation, Phenotype harmonization, Polygenic risk, Zoology, Neurosciences, Genetics & Heredity, Biomedical and clinical sciences, Health sciences
Abstract

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Published
2016

12. Whole‐genome sequencing identifies EN1 as a determinant of bone density and fracture

Author

Zheng, Hou‐Feng, Forgetta, Vincenzo, Hsu, Yi‐Hsiang, Estrada, Karol, Rosello‐Diez, Alberto, Leo, Paul J, Dahia, Chitra L, Park‐Min, Kyung Hyun, Tobias, Jonathan H, Kooperberg, Charles, Kleinman, Aaron, Styrkarsdottir, Unnur, Liu, Ching‐Ti, Uggla, Charlotta, Evans, Daniel S, Nielson, Carrie M, Walter, Klaudia, Pettersson‐Kymmer, Ulrika, McCarthy, Shane, Eriksson, Joel, Kwan, Tony, Jhamai, Mila, Trajanoska, Katerina, Memari, Yasin, Min, Josine, Huang, Jie, Danecek, Petr, Wilmot, Beth, Li, Rui, Chou, Wen‐Chi, Mokry, Lauren E, Moayyeri, Alireza, Claussnitzer, Melina, Cheng, Chia‐Ho, Cheung, Warren, Medina‐Gómez, Carolina, Ge, Bing, Chen, Shu‐Huang, Choi, Kwangbom, Oei, Ling, Fraser, James, Kraaij, Robert, Hibbs, Matthew A, Gregson, Celia L, Paquette, Denis, Hofman, Albert, Wibom, Carl, Tranah, Gregory J, Marshall, Mhairi, Gardiner, Brooke B, Cremin, Katie, Auer, Paul, Hsu, Li, Ring, Sue, Tung, Joyce Y, Thorleifsson, Gudmar, Enneman, Anke W, van Schoor, Natasja M, de Groot, Lisette CPGM, van der Velde, Nathalie, Melin, Beatrice, Kemp, John P, Christiansen, Claus, Sayers, Adrian, Zhou, Yanhua, Calderari, Sophie, van Rooij, Jeroen, Carlson, Chris, Peters, Ulrike, Berlivet, Soizik, Dostie, Josée, Uitterlinden, Andre G, Williams, Stephen R, Farber, Charles, Grinberg, Daniel, LaCroix, Andrea Z, Haessler, Jeff, Chasman, Daniel I, Giulianini, Franco, Rose, Lynda M, Ridker, Paul M, Eisman, John A, Nguyen, Tuan V, Center, Jacqueline R, Nogues, Xavier, Garcia‐Giralt, Natalia, Launer, Lenore L, Gudnason, Vilmunder, Mellström, Dan, Vandenput, Liesbeth, Amin, Najaf, van Duijn, Cornelia M, Karlsson, Magnus K, Ljunggren, Östen, Svensson, Olle, Hallmans, Göran, Rousseau, François, Giroux, Sylvie, Bussière, Johanne, and Arp, Pascal P

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Human Genome, Biotechnology, Osteoporosis, Stem Cell Research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Underpinning research, Musculoskeletal, Injuries and accidents, Animals, Bone Density, Bone and Bones, Disease Models, Animal, Europe, Exome, Female, Fractures, Bone, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genomics, Genotype, Homeodomain Proteins, Humans, Mice, Sequence Analysis, DNA, White People, Wnt Proteins, AOGC Consortium, UK10K Consortium, General Science & Technology
Abstract

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.

Published
2015

13. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder

Author

de Moor, Marleen HM, van den Berg, Stéphanie M, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Vasquez, Alejandro Arias, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Smith, George Davey, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Porteous, David, Minelli, Alessandra, Palmer, Abraham A, Rujescu, Dan, Ciullo, Marina, Hayward, Caroline, and Rudan, Igor

Subjects
Biological Sciences, Genetics, Biological Psychology, Epidemiology, Social and Personality Psychology, Health Sciences, Psychology, Mental Health, Brain Disorders, Major Depressive Disorder, Serious Mental Illness, Human Genome, Mental Illness, Depression, 2.1 Biological and endogenous factors, Mental health, Adaptor Proteins, Signal Transducing, Anxiety Disorders, Cell Adhesion Molecules, Cell Adhesion Molecules, Neuronal, Depressive Disorder, Major, Genetic Predisposition to Disease, Genome-Wide Association Study, Guanylate Kinases, Humans, Multifactorial Inheritance, Neuroticism, Personality, Polymorphism, Single Nucleotide, Risk Factors, Genetics of Personality Consortium, Other Medical and Health Sciences, Cognitive Sciences, Clinical sciences, Clinical and health psychology
Abstract

ImportanceNeuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).ObjectivesTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.Design, setting, and participantsGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.Main outcomes and measuresNeuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.ResultsA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12

Published
2015

14. Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

Author

Genetics of Personality Consortium, de Moor, Marleen HM, van den Berg, Stéphanie M, Verweij, Karin JH, Krueger, Robert F, Luciano, Michelle, Arias Vasquez, Alejandro, Matteson, Lindsay K, Derringer, Jaime, Esko, Tõnu, Amin, Najaf, Gordon, Scott D, Hansell, Narelle K, Hart, Amy B, Seppälä, Ilkka, Huffman, Jennifer E, Konte, Bettina, Lahti, Jari, Lee, Minyoung, Miller, Mike, Nutile, Teresa, Tanaka, Toshiko, Teumer, Alexander, Viktorin, Alexander, Wedenoja, Juho, Abecasis, Goncalo R, Adkins, Daniel E, Agrawal, Arpana, Allik, Jüri, Appel, Katja, Bigdeli, Timothy B, Busonero, Fabio, Campbell, Harry, Costa, Paul T, Davey Smith, George, Davies, Gail, de Wit, Harriet, Ding, Jun, Engelhardt, Barbara E, Eriksson, Johan G, Fedko, Iryna O, Ferrucci, Luigi, Franke, Barbara, Giegling, Ina, Grucza, Richard, Hartmann, Annette M, Heath, Andrew C, Heinonen, Kati, Henders, Anjali K, Homuth, Georg, Hottenga, Jouke-Jan, Iacono, William G, Janzing, Joost, Jokela, Markus, Karlsson, Robert, Kemp, John P, Kirkpatrick, Matthew G, Latvala, Antti, Lehtimäki, Terho, Liewald, David C, Madden, Pamela AF, Magri, Chiara, Magnusson, Patrik KE, Marten, Jonathan, Maschio, Andrea, Medland, Sarah E, Mihailov, Evelin, Milaneschi, Yuri, Montgomery, Grant W, Nauck, Matthias, Ouwens, Klaasjan G, Palotie, Aarno, Pettersson, Erik, Polasek, Ozren, Qian, Yong, Pulkki-Råback, Laura, Raitakari, Olli T, Realo, Anu, Rose, Richard J, Ruggiero, Daniela, Schmidt, Carsten O, Slutske, Wendy S, Sorice, Rossella, Starr, John M, St Pourcain, Beate, Sutin, Angelina R, Timpson, Nicholas J, Trochet, Holly, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Wouda, Jasper, Wright, Margaret J, Zgaga, Lina, Porteous, David, Minelli, Alessandra, Palmer, Abraham A, Rujescu, Dan, Ciullo, Marina, and Hayward, Caroline

Subjects
Genetics of Personality Consortium, Humans, Genetic Predisposition to Disease, Cell Adhesion Molecules, Neuronal, Risk Factors, Personality, Anxiety Disorders, Depressive Disorder, Major, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Neuroticism, Adaptor Proteins, Signal Transducing, Cell Adhesion Molecules, Guanylate Kinases, Neuronal, Depressive Disorder, Major, Polymorphism, Single Nucleotide, Adaptor Proteins, Signal Transducing, Other Medical and Health Sciences, Psychology, Cognitive Sciences
Abstract

ImportanceNeuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).ObjectivesTo identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD.Design, setting, and participantsGenome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014.Main outcomes and measuresNeuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts.ResultsA genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P = 9.26 × 10-9 in the discovery meta-analysis). This association was not replicated (P = .32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P = 2.38 × 10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09 × 10-12

Published
2015

15. Measurements of nitrogen fixation in the oligotrophic North Pacific Subtropical Gyre using a free-drifting submersible incubation device

Author

Bombar, Deniz, Taylor, Craig D, Wilson, Samuel T, Robidart, Julie C, Rabines, Ariel, Turk-Kubo, Kendra A, Kemp, John N, Karl, David M, and Zehr, Jonathan P

Subjects
Life Below Water, nitrogen fixation, in situ device, Pacific Ocean, diazotroph, Ecology, Zoology, Fisheries Sciences, Marine Biology & Hydrobiology
Abstract

One challenge in field-based marine microbial ecology is to achieve sufficient spatial resolution to obtain representative information about microbial distributions and biogeochemical processes. The challenges are exacerbated when conducting rate measurements of biological processes due to potential perturbations during sampling and incubation. Here we present the first application of a robotic microlaboratory, the 4 L-submersible incubation device (SID), for conducting in situ measurements of the rates of biological nitrogen (N2) fixation (BNF). The free-drifting autonomous instrument obtains samples from the water column that are incubated in situ after the addition of 15N2 tracer. After each of up to four consecutive incubation experiments, the 4-L sample is filtered and chemically preserved. Measured BNF rates from two deployments of the SID in the oligotrophic North Pacific ranged from 0.8 to 2.8 nmol N L-1 day-1, values comparable with simultaneous rate measurements obtained using traditional conductivity-temperature-depth (CTD)-rosette sampling followed by on-deck or in situ incubation. Future deployments of the SID will help to better resolve spatial variability of oceanic BNF, particularly in areas where recovery of seawater samples by CTD compromises their integrity, e.g. anoxic habitats.

Published
2015

16. Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease

Author

Youlten, Scott E., Kemp, John P., Logan, John G., Ghirardello, Elena J., Sergio, Claudio M., Dack, Michael R. G., Guilfoyle, Siobhan E., Leitch, Victoria D., Butterfield, Natalie C., Komla-Ebri, Davide, Chai, Ryan C., Corr, Alexander P., Smith, James T., Mohanty, Sindhu T., Morris, John A., McDonald, Michelle M., Quinn, Julian M. W., McGlade, Amelia R., Bartonicek, Nenad, Jansson, Matt, Hatzikotoulas, Konstantinos, Irving, Melita D., Beleza-Meireles, Ana, Rivadeneira, Fernando, Duncan, Emma, Richards, J. Brent, Adams, David J., Lelliott, Christopher J., Brink, Robert, Phan, Tri Giang, Eisman, John A., Evans, David M., Zeggini, Eleftheria, Baldock, Paul A., Bassett, J. H. Duncan, Williams, Graham R., and Croucher, Peter I.

Published
2021
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18. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author

Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Snieder, Harold, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Benjamin, Emelia, Chasman, Daniel I., Dehghan, Abbas, Ahluwalia, Tarunveer Singh, Meigs, James, Tracy, Russell, Ligthart, Symen, Bis, Josh, Eiriksdottir, Gudny, Pankratz, Nathan, Gross, Myron, Rainer, Alex, Wilson, James G., Psaty, Bruce M., Dupuis, Josee, Prins, Bram, Vaso, Urmo, Stathopoulou, Maria, Lehtimaki, Terho, Koenig, Wolfgang, Jamshidi, Yalda, Siest, Sophie, Abbasi, Ali, Uitterlinden, Andre G., Abdollahi, Mohammadreza, Schnabel, Renate, Schick, Ursula M., Nolte, Ilja M., Kraja, Aldi, Hsu, Yi-Hsiang, Tylee, Daniel S., Zwicker, Alyson, Uher, Rudolf, Davey-Smith, George, Morrison, Alanna C., Hicks, Andrew, van Duijn, Cornelia M., Ward-Caviness, Cavin, Boerwinkle, Eric, Rotter, J., Rice, Ken, Lange, Leslie, Perola, Markus, de Geus, Eco, Morris, Andrew P., Makela, Kari Matti, Stacey, David, Eriksson, Johan, Frayling, Tim M., Slagboom, Eline P., Vaez, Ahmad, Võsa, Urmo, Stathopoulou, Maria G., de Vries, Paul S., Prins, Bram P., Van der Most, Peter J., Tanaka, Toshiko, Naderi, Elnaz, Rose, Lynda M., Wu, Ying, Karlsson, Robert, Barbalic, Maja, Lin, Honghuang, Pool, René, Zhu, Gu, Macé, Aurélien, Sidore, Carlo, Trompet, Stella, Mangino, Massimo, Sabater-Lleal, Maria, Kemp, John P., Kacprowski, Tim, Verweij, Niek, Smith, Albert V., Huang, Tao, Marzi, Carola, Feitosa, Mary F., Lohman, Kurt K., Kleber, Marcus E., Milaneschi, Yuri, Mueller, Christian, Huq, Mahmudul, Vlachopoulou, Efthymia, Lyytikäinen, Leo-Pekka, Oldmeadow, Christopher, Deelen, Joris, Zhao, Jing Hua, Feenstra, Bjarke, Amini, Marzyeh, Lahti, Jari, Schraut, Katharina E., Fornage, Myriam, Suktitipat, Bhoom, Chen, Wei-Min, Li, Xiaohui, Nutile, Teresa, Malerba, Giovanni, Luan, Jian’an, Bak, Tom, Schork, Nicholas, Del Greco M., Fabiola, Thiering, Elisabeth, Mahajan, Anubha, Marioni, Riccardo E., Mihailov, Evelin, Eriksson, Joel, Ozel, Ayse Bilge, Zhang, Weihua, Nethander, Maria, Cheng, Yu-Ching, Aslibekyan, Stella, Ang, Wei, Gandin, Ilaria, Yengo, Loïc, Portas, Laura, Kooperberg, Charles, Hofer, Edith, Rajan, Kumar B., Schurmann, Claudia, den Hollander, Wouter, Ahluwalia, Tarunveer S., Zhao, Jing, Draisma, Harmen H.M., Ford, Ian, Timpson, Nicholas, Teumer, Alexander, Huang, Hongyan, Wahl, Simone, Liu, YongMei, Huang, Jie, Uh, Hae-Won, Geller, Frank, Joshi, Peter K., Yanek, Lisa R., Trabetti, Elisabetta, Lehne, Benjamin, Vozzi, Diego, Verbanck, Marie, Biino, Ginevra, Saba, Yasaman, Meulenbelt, Ingrid, O’Connell, Jeff R., Laakso, Markku, Giulianini, Franco, Magnusson, Patrik K.E., Ballantyne, Christie M., Hottenga, Jouke Jan, Montgomery, Grant W., Rivadineira, Fernando, Rueedi, Rico, Steri, Maristella, Herzig, Karl-Heinz, Stott, David J., Menni, Cristina, Frånberg, Mattias, St. Pourcain, Beate, Felix, Stephan B., Pers, Tune H., Bakker, Stephan J.L., Kraft, Peter, Peters, Annette, Vaidya, Dhananjay, Delgado, Graciela, Smit, Johannes H., Großmann, Vera, Sinisalo, Juha, Seppälä, Ilkka, Williams, Stephen R., Holliday, Elizabeth G., Moed, Matthijs, Langenberg, Claudia, Räikkönen, Katri, Ding, Jingzhong, Campbell, Harry, Sale, Michele M., Chen, Yii-Der I., James, Alan L., Ruggiero, Daniela, Soranzo, Nicole, Hartman, Catharina A., Smith, Erin N., Berenson, Gerald S., Fuchsberger, Christian, Hernandez, Dena, Tiesler, Carla M.T., Giedraitis, Vilmantas, Liewald, David, Fischer, Krista, Mellström, Dan, Larsson, Anders, Wang, Yunmei, Scott, William R., Lorentzon, Matthias, Beilby, John, Ryan, Kathleen A., Pennell, Craig E., Vuckovic, Dragana, Balkau, Beverly, Concas, Maria Pina, Schmidt, Reinhold, Mendes de Leon, Carlos F., Bottinger, Erwin P., Kloppenburg, Margreet, Paternoster, Lavinia, Boehnke, Michael, Musk, A.W., Willemsen, Gonneke, Evans, David M., Madden, Pamela A.F., Kähönen, Mika, Kutalik, Zoltán, Zoledziewska, Magdalena, Karhunen, Ville, Kritchevsky, Stephen B., Sattar, Naveed, Lachance, Genevieve, Clarke, Robert, Harris, Tamara B., Raitakari, Olli T., Attia, John R., van Heemst, Diana, Kajantie, Eero, Sorice, Rossella, Gambaro, Giovanni, Scott, Robert A., Hicks, Andrew A., Ferrucci, Luigi, Standl, Marie, Lindgren, Cecilia M., Starr, John M., Karlsson, Magnus, Lind, Lars, Li, Jun Z., Chambers, John C., Mori, Trevor A., de Geus, Eco J.C.N., Heath, Andrew C., Martin, Nicholas G., Auvinen, Juha, Buckley, Brendan M., de Craen, Anton J.M., Waldenberger, Melanie, Strauch, Konstantin, Meitinger, Thomas, Scott, Rodney J., McEvoy, Mark, Beekman, Marian, Bombieri, Cristina, Ridker, Paul M., Mohlke, Karen L., Pedersen, Nancy L., Boomsma, Dorret I., Whitfield, John B., Strachan, David P., Hofman, Albert, Vollenweider, Peter, Cucca, Francesco, Jarvelin, Marjo-Riitta, Jukema, J. Wouter, Spector, Tim D., Hamsten, Anders, Zeller, Tanja, Uitterlinden, André G., Nauck, Matthias, Gudnason, Vilmundur, Qi, Lu, Grallert, Harald, Borecki, Ingrid B., Rotter, Jerome I., März, Winfried, Wild, Philipp S., Lokki, Marja-Liisa, Boyle, Michael, Salomaa, Veikko, Melbye, Mads, Eriksson, Johan G., Wilson, James F., Penninx, Brenda W.J.H., Becker, Diane M., Worrall, Bradford B., Gibson, Greg, Krauss, Ronald M., Ciullo, Marina, Zaza, Gianluigi, Wareham, Nicholas J., Oldehinkel, Albertine J., Palmer, Lyle J., Murray, Sarah S., Pramstaller, Peter P., Bandinelli, Stefania, Heinrich, Joachim, Ingelsson, Erik, Deary, Ian J., Mägi, Reedik, Vandenput, Liesbeth, Desch, Karl C., Kooner, Jaspal S., Ohlsson, Claes, Hayward, Caroline, Lehtimäki, Terho, Shuldiner, Alan R., Arnett, Donna K., Beilin, Lawrence J., Robino, Antonietta, Froguel, Philippe, Pirastu, Mario, Jess, Tine, Loos, Ruth J.F., Evans, Denis A., Schmidt, Helena, Smith, George Davey, Slagboom, P. Eline, Tracy, Russell P., Visvikis-Siest, Sophie, Reiner, Alex P., Bis, Joshua C., Franco, Oscar H., Benjamin, Emelia J., and Dupuis, Josée

Published
2018
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19. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

Author

Cheng, Ching-Yu, Schache, Maria, Ikram, M Kamran, Young, Terri L, Guggenheim, Jeremy A, Vitart, Veronique, MacGregor, Stuart, Verhoeven, Virginie JM, Barathi, Veluchamy A, Liao, Jiemin, Hysi, Pirro G, Bailey-Wilson, Joan E, St. Pourcain, Beate, Kemp, John P, McMahon, George, Timpson, Nicholas J, Evans, David M, Montgomery, Grant W, Mishra, Aniket, Wang, Ya Xing, Wang, Jie Jin, Rochtchina, Elena, Polasek, Ozren, Wright, Alan F, Amin, Najaf, van Leeuwen, Elisabeth M, Wilson, James F, Pennell, Craig E, van Duijn, Cornelia M, de Jong, Paulus TVM, Vingerling, Johannes R, Zhou, Xin, Chen, Peng, Li, Ruoying, Tay, Wan-Ting, Zheng, Yingfeng, Chew, Merwyn, Error and Myopia, Consortium for Refractive, Cohort, 1958 British Birth, Rahi, Jugnoo S, cohort, Aichi, Yoshimura, Nagahisa, Yamashiro, Kenji, Miyake, Masahiro, ALIENOR, Delcourt, Cécile, Maubaret, Cecilia, ALSPAC, Williams, Cathy, Northstone, Kate, Ring, Susan M, Davey-Smith, George, ANZRAG, Craig, Jamie E, Burdon, Kathryn P, Fogarty, Rhys D, AREDS1a, Iyengar, Sudha K, Igo, Robert P, Chew, Emily, Janmahasathian, Sarayut, AREDS1b, AREDS1c, Stambolian, Dwight, Wilson, Joan E Bailey, BATS, Lu, Yi, Study, Beijing Eye, Jonas, Jost B, Xu, Liang, Saw, Seang-Mei, BMES, Baird, Paul N, Mitchell, Paul, CIEMS, Nangia, Vinay, CROATIA-Korčula, Hayward, Caroline, CROATIA-Split, Campbell, Harry, CROATIA-Vis, Rudan, Igor, Vatavuk, Zoran, DCCT, Paterson, Andrew D, Hosseini, S Mohsen, GWAS, FECD Fuchs Dystrophy, Fondran, Jeremy R, Study, Myopia, Feng, Sheng, and Study, Erasmus Rucphen Family

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Allied Health and Rehabilitation Science, Health Sciences, Ophthalmology and Optometry, Human Genome, Eye Disease and Disorders of Vision, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Eye, Adolescent, Adult, Aged, Asian People, Axial Length, Eye, Eye Proteins, Female, Gene Expression, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Refractive Errors, Signal Transduction, White People, Consortium for Refractive Error and Myopia, Fuchs' Genetics Multi-Center Study Group, Wellcome Trust Case Control Consortium 2, Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions, and Complications Research Group, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.

Published
2013

20. A genome-wide association meta-analysis identifies new childhood obesity loci

Author

Bradfield, Jonathan P, Taal, H Rob, Timpson, Nicholas J, Scherag, Andre, Lecoeur, Cecile, Warrington, Nicole M, Hypponen, Elina, Holst, Claus, Valcarcel, Beatriz, Thiering, Elisabeth, Salem, Rany M, Schumacher, Fredrick R, Cousminer, Diana L, Sleiman, Patrick MA, Zhao, Jianhua, Berkowitz, Robert I, Vimaleswaran, Karani S, Jarick, Ivonne, Pennell, Craig E, Evans, David M, St Pourcain, Beate, Berry, Diane J, Mook-Kanamori, Dennis O, Hofman, Albert, Rivadeneira, Fernando, Uitterlinden, Andre G, van Duijn, Cornelia M, van der Valk, Ralf JP, de Jongste, Johan C, Postma, Dirkje S, Boomsma, Dorret I, Gauderman, W James, Hassanein, Mohamed T, Lindgren, Cecilia M, Magi, Reedik, Boreham, Colin AG, Neville, Charlotte E, Moreno, Luis A, Elliott, Paul, Pouta, Anneli, Hartikainen, Anna-Liisa, Li, Mingyao, Raitakari, Olli, Lehtimaki, Terho, Eriksson, Johan G, Palotie, Aarno, Dallongeville, Jean, Das, Shikta, Deloukas, Panos, McMahon, George, Ring, Susan M, Kemp, John P, Buxton, Jessica L, Blakemore, Alexandra IF, Bustamante, Mariona, Guxens, Monica, Hirschhorn, Joel N, Gillman, Matthew W, Kreiner-Moller, Eskil, Bisgaard, Hans, Gilliland, Frank D, Heinrich, Joachim, Wheeler, Eleanor, Barroso, Ines, O'Rahilly, Stephen, Meirhaeghe, Aline, Sorensen, Thorkild IA, Power, Chris, Palmer, Lyle J, Hinney, Anke, Widen, Elisabeth, Farooqi, I Sadaf, McCarthy, Mark I, Froguel, Philippe, Meyre, David, Hebebrand, Johannes, Jarvelin, Marjo-Riitta, Jaddoe, Vincent WV, Smith, George Davey, Hakonarson, Hakon, and Grant, Struan FA

Subjects
Biological Sciences, Genetics, Pediatric, Nutrition, Obesity, Human Genome, Metabolic and endocrine, Oral and gastrointestinal, Stroke, Cancer, Cardiovascular, Adolescent, Adult, Body Mass Index, Case-Control Studies, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Young Adult, Early Growth Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (

Published
2012

21. Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits

Author

Tachmazidou, Ioanna, Süveges, Dániel, Min, Josine L., Ritchie, Graham R.S., Steinberg, Julia, Walter, Klaudia, Iotchkova, Valentina, Schwartzentruber, Jeremy, Huang, Jie, Memari, Yasin, McCarthy, Shane, Crawford, Andrew A., Bombieri, Cristina, Cocca, Massimiliano, Farmaki, Aliki-Eleni, Gaunt, Tom R., Jousilahti, Pekka, Kooijman, Marjolein N., Lehne, Benjamin, Malerba, Giovanni, Männistö, Satu, Matchan, Angela, Medina-Gomez, Carolina, Metrustry, Sarah J., Nag, Abhishek, Ntalla, Ioanna, Paternoster, Lavinia, Rayner, Nigel W., Sala, Cinzia, Scott, William R., Shihab, Hashem A., Southam, Lorraine, St Pourcain, Beate, Traglia, Michela, Trajanoska, Katerina, Zaza, Gialuigi, Zhang, Weihua, Artigas, María S., Bansal, Narinder, Benn, Marianne, Chen, Zhongsheng, Danecek, Petr, Lin, Wei-Yu, Locke, Adam, Luan, Jian’an, Manning, Alisa K., Mulas, Antonella, Sidore, Carlo, Tybjaerg-Hansen, Anne, Varbo, Anette, Zoledziewska, Magdalena, Finan, Chris, Hatzikotoulas, Konstantinos, Hendricks, Audrey E., Kemp, John P., Moayyeri, Alireza, Panoutsopoulou, Kalliope, Szpak, Michal, Wilson, Scott G., Boehnke, Michael, Cucca, Francesco, Di Angelantonio, Emanuele, Langenberg, Claudia, Lindgren, Cecilia, McCarthy, Mark I., Morris, Andrew P., Nordestgaard, Børge G., Scott, Robert A., Tobin, Martin D., Wareham, Nicholas J., Burton, Paul, Chambers, John C., Smith, George Davey, Dedoussis, George, Felix, Janine F., Franco, Oscar H., Gambaro, Giovanni, Gasparini, Paolo, Hammond, Christopher J., Hofman, Albert, Jaddoe, Vincent W.V., Kleber, Marcus, Kooner, Jaspal S., Perola, Markus, Relton, Caroline, Ring, Susan M., Rivadeneira, Fernando, Salomaa, Veikko, Spector, Timothy D., Stegle, Oliver, Toniolo, Daniela, Uitterlinden, André G., Barroso, Inês, Greenwood, Celia M.T., Perry, John R.B., Walker, Brian R., Butterworth, Adam S., Xue, Yali, Durbin, Richard, Small, Kerrin S., Soranzo, Nicole, Timpson, Nicholas J., and Zeggini, Eleftheria

Published
2017
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23. Femoral neck width genetic risk score is a novel independent risk factor for hip fractures.

Author

Tobias, Jonathan H, Nethander, Maria, Faber, Benjamin G, Heppenstall, Sophie V, Ebsim, Raja, Cootes, Tim, Lindner, Claudia, Saunders, Fiona R, Gregory, Jenny S, Aspden, Richard M, Harvey, Nicholas C, Kemp, John P, Frysz, Monika, and Ohlsson, Claes

Abstract

Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29–1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30–1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n  = 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05–1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06–1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and its Risk Factors: Evidence From a Genome‐Wide Association Meta‐Analysis Followed by Mendelian Randomization

Author

Zheng, Jie, primary, Wheeler, Eleanor, additional, Pietzner, Maik, additional, Andlauer, Till F. M., additional, Yau, Michelle S., additional, Hartley, April E., additional, Brumpton, Ben Michael, additional, Rasheed, Humaira, additional, Kemp, John P., additional, Frysz, Monika, additional, Robinson, Jamie, additional, Reppe, Sjur, additional, Prijatelj, Vid, additional, Gautvik, Kaare M., additional, Falk, Louise, additional, Maerz, Winfried, additional, Gergei, Ingrid, additional, Peyser, Patricia A., additional, Kavousi, Maryam, additional, de Vries, Paul S., additional, Miller, Clint L., additional, Bos, Maxime, additional, van der Laan, Sander W., additional, Malhotra, Rajeev, additional, Herrmann, Markus, additional, Scharnagl, Hubert, additional, Kleber, Marcus, additional, Dedoussis, George, additional, Zeggini, Eleftheria, additional, Nethander, Maria, additional, Ohlsson, Claes, additional, Lorentzon, Mattias, additional, Wareham, Nick, additional, Langenberg, Claudia, additional, Holmes, Michael V., additional, Davey Smith, George, additional, and Tobias, Jonathan H., additional

Published
2023
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25. Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis

Author

Medina-Gomez, Carolina, primary, Mullin, Benjamin H., additional, Chesi, Alessandra, additional, Prijatelj, Vid, additional, Kemp, John P., additional, Shochat-Carvalho, Chen, additional, Trajanoska, Katerina, additional, Wang, Carol, additional, Joro, Raimo, additional, Evans, Tavia E., additional, Schraut, Katharina E., additional, Li-Gao, Ruifang, additional, Ahluwalia, Tarunveer S., additional, Zillikens, M. Carola, additional, Zhu, Kun, additional, Mook-Kanamori, Dennis O., additional, Evans, Daniel S., additional, Nethander, Maria, additional, Knol, Maria J., additional, Thorleifsson, Gudmar, additional, Prokic, Ivana, additional, Zemel, Babette, additional, Broer, Linda, additional, McGuigan, Fiona E., additional, van Schoor, Natasja M., additional, Reppe, Sjur, additional, Pawlak, Mikolaj A., additional, Ralston, Stuart H., additional, van der Velde, Nathalie, additional, Lorentzon, Mattias, additional, Stefansson, Kari, additional, Adams, Hieab H. H., additional, Wilson, Scott G., additional, Ikram, M. Arfan, additional, Walsh, John P., additional, Lakka, Timo A., additional, Gautvik, Kaare M., additional, Wilson, James F., additional, Orwoll, Eric S., additional, van Duijn, Cornelia M., additional, Bønnelykke, Klaus, additional, Uitterlinden, Andre G., additional, Styrkársdóttir, Unnur, additional, Akesson, Kristina E., additional, Spector, Timothy D., additional, Tobias, Jonathan H., additional, Ohlsson, Claes, additional, Felix, Janine F., additional, Bisgaard, Hans, additional, Grant, Struan F. A., additional, Richards, J. Brent, additional, Evans, David M., additional, van der Eerden, Bram, additional, van de Peppel, Jeroen, additional, Ackert-Bicknell, Cheryl, additional, Karasik, David, additional, Kague, Erika, additional, and Rivadeneira, Fernando, additional

Published
2023
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26. A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Pediatric Cohorts

Author

Middeldorp, Christel M., Hammerschlag, Anke R., Ouwens, Klaasjan G., Groen-Blokhuis, Maria M., St. Pourcain, Beate, Greven, Corina U., Pappa, Irene, Tiesler, Carla M.T., Ang, Wei, Nolte, Ilja M., Vilor-Tejedor, Natalia, Bacelis, Jonas, Ebejer, Jane L., Zhao, Huiying, Davies, Gareth E., Ehli, Erik A., Evans, David M., Fedko, Iryna O., Guxens, Mònica, Hottenga, Jouke-Jan, Hudziak, James J., Jugessur, Astanand, Kemp, John P., Krapohl, Eva, Martin, Nicholas G., Murcia, Mario, Myhre, Ronny, Ormel, Johan, Ring, Susan M., Standl, Marie, Stergiakouli, Evie, Stoltenberg, Camilla, Thiering, Elisabeth, Timpson, Nicholas J., Trzaskowski, Maciej, van der Most, Peter J., Wang, Carol, Nyholt, Dale R., Medland, Sarah E., Neale, Benjamin, Jacobsson, Bo, Sunyer, Jordi, Hartman, Catharina A., Whitehouse, Andrew J.O., Pennell, Craig E., Heinrich, Joachim, Plomin, Robert, Davey Smith, George, Tiemeier, Henning, Posthuma, Danielle, and Boomsma, Dorret I.

Published
2016
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27. Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and its Risk Factors:Evidence From a Genome-Wide Association Meta-Analysis Followed by Mendelian Randomization

Author

Zheng, Jie, Wheeler, Eleanor, Pietzner, Maik, Andlauer, Till F.M., Yau, Michelle S., Hartley, April E., Brumpton, Ben Michael, Rasheed, Humaira, Kemp, John P., Frysz, Monika, Robinson, Jamie, Reppe, Sjur, Prijatelj, Vid, Gautvik, Kaare M., Falk, Louise, Maerz, Winfried, Gergei, Ingrid, Peyser, Patricia A., Kavousi, Maryam, de Vries, Paul S., Miller, Clint L., Bos, Maxime, van der Laan, Sander W., Malhotra, Rajeev, Herrmann, Markus, Scharnagl, Hubert, Kleber, Marcus, Dedoussis, George, Zeggini, Eleftheria, Nethander, Maria, Ohlsson, Claes, Lorentzon, Mattias, Wareham, Nick, Langenberg, Claudia, Holmes, Michael V., Davey Smith, George, Tobias, Jonathan H., Zheng, Jie, Wheeler, Eleanor, Pietzner, Maik, Andlauer, Till F.M., Yau, Michelle S., Hartley, April E., Brumpton, Ben Michael, Rasheed, Humaira, Kemp, John P., Frysz, Monika, Robinson, Jamie, Reppe, Sjur, Prijatelj, Vid, Gautvik, Kaare M., Falk, Louise, Maerz, Winfried, Gergei, Ingrid, Peyser, Patricia A., Kavousi, Maryam, de Vries, Paul S., Miller, Clint L., Bos, Maxime, van der Laan, Sander W., Malhotra, Rajeev, Herrmann, Markus, Scharnagl, Hubert, Kleber, Marcus, Dedoussis, George, Zeggini, Eleftheria, Nethander, Maria, Ohlsson, Claes, Lorentzon, Mattias, Wareham, Nick, Langenberg, Claudia, Holmes, Michael V., Davey Smith, George, and Tobias, Jonathan H.

Published
2023

28. A Genome-Wide Association Study Meta-Analysis of Alpha Angle Suggests Cam-Type Morphology May Be a Specific Feature of Hip Osteoarthritis in Older Adults

Author

Faber, Benjamin G., Frysz, Monika, Hartley, April E., Ebsim, Raja, Boer, Cindy G., Saunders, Fiona R., Gregory, Jennifer S., Aspden, Richard M., Harvey, Nicholas C., Southam, Lorraine, Giles, William, Le Maitre, Christine L., Wilkinson, J. Mark, van Meurs, Joyce B.J., Zeggini, Eleftheria, Cootes, Timothy, Lindner, Claudia, Kemp, John P., Davey Smith, George, Tobias, Jonathan H., Faber, Benjamin G., Frysz, Monika, Hartley, April E., Ebsim, Raja, Boer, Cindy G., Saunders, Fiona R., Gregory, Jennifer S., Aspden, Richard M., Harvey, Nicholas C., Southam, Lorraine, Giles, William, Le Maitre, Christine L., Wilkinson, J. Mark, van Meurs, Joyce B.J., Zeggini, Eleftheria, Cootes, Timothy, Lindner, Claudia, Kemp, John P., Davey Smith, George, and Tobias, Jonathan H.

Published
2023

29. Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis

Author

Medina-Gomez, Carolina, Mullin, Benjamin H., Chesi, Alessandra, Prijatelj, Vid, Kemp, John P., Shochat-Carvalho, Chen, Trajanoska, Katerina, Wang, Carol, Joro, Raimo, Evans, Tavia E., Schraut, Katharina E., Li-Gao, Ruifang, Ahluwalia, Tarunveer S., Zillikens, M. Carola, Zhu, Kun, Mook-Kanamori, Dennis O., Evans, Daniel S., Nethander, Maria, Knol, Maria J., Thorleifsson, Gudmar, Prokic, Ivana, Zemel, Babette, Broer, Linda, McGuigan, Fiona E., van Schoor, Natasja M., Reppe, Sjur, Pawlak, Mikolaj A., Ralston, Stuart H., van der Velde, Nathalie, Lorentzon, Mattias, Stefansson, Kari, Adams, Hieab H.H., Wilson, Scott G., Ikram, M. Arfan, Walsh, John P., Lakka, Timo A., Gautvik, Kaare M., Wilson, James F., Orwoll, Eric S., van Duijn, Cornelia M., Bønnelykke, Klaus, Uitterlinden, Andre G., Styrkársdóttir, Unnur, Akesson, Kristina E., Spector, Timothy D., Tobias, Jonathan H., Ohlsson, Claes, Felix, Janine F., Bisgaard, Hans, Grant, Struan F.A., Richards, J. Brent, Evans, David M., van der Eerden, Bram, van de Peppel, Jeroen, Ackert-Bicknell, Cheryl, Karasik, David, Kague, Erika, Rivadeneira, Fernando, Medina-Gomez, Carolina, Mullin, Benjamin H., Chesi, Alessandra, Prijatelj, Vid, Kemp, John P., Shochat-Carvalho, Chen, Trajanoska, Katerina, Wang, Carol, Joro, Raimo, Evans, Tavia E., Schraut, Katharina E., Li-Gao, Ruifang, Ahluwalia, Tarunveer S., Zillikens, M. Carola, Zhu, Kun, Mook-Kanamori, Dennis O., Evans, Daniel S., Nethander, Maria, Knol, Maria J., Thorleifsson, Gudmar, Prokic, Ivana, Zemel, Babette, Broer, Linda, McGuigan, Fiona E., van Schoor, Natasja M., Reppe, Sjur, Pawlak, Mikolaj A., Ralston, Stuart H., van der Velde, Nathalie, Lorentzon, Mattias, Stefansson, Kari, Adams, Hieab H.H., Wilson, Scott G., Ikram, M. Arfan, Walsh, John P., Lakka, Timo A., Gautvik, Kaare M., Wilson, James F., Orwoll, Eric S., van Duijn, Cornelia M., Bønnelykke, Klaus, Uitterlinden, Andre G., Styrkársdóttir, Unnur, Akesson, Kristina E., Spector, Timothy D., Tobias, Jonathan H., Ohlsson, Claes, Felix, Janine F., Bisgaard, Hans, Grant, Struan F.A., Richards, J. Brent, Evans, David M., van der Eerden, Bram, van de Peppel, Jeroen, Ackert-Bicknell, Cheryl, Karasik, David, Kague, Erika, and Rivadeneira, Fernando

Abstract

Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases., Skull bone mineral density (SK-BMD) provides a suitable trait for the discovery of key genes in bone biology, particularly to intramembranous ossification, not captured at other skeletal sites. We perform a genome-wide association meta-analysis (n ~ 43,800) of SK-BMD, identifying 59 loci, collectively explaining 12.5% of the trait variance. Association signals cluster within gene-sets involved in skeletal development and osteoporosis. Among the four novel loci (ZIC1, PRKAR1A, AZIN1/ATP6V1C1, GLRX3), there are factors implicated in intramembranous ossification and as we show, inherent to craniosynostosis processes. Functional follow-up in zebrafish confirms the importance of ZIC1 on cranial suture patterning. Likewise, we observe abnormal cranial bone initiation that culminates in ectopic sutures and reduced BMD in mosaic atp6v1c1 knockouts. Mosaic prkar1a knockouts present asymmetric bone growth and, conversely, elevated BMD. In light of this evidence linking SK-BMD loci to craniofacial abnormalities, our study provides new insight into the pathophysiology, diagnosis and treatment of skeletal diseases.

Published
2023

30. The identification of distinct protective and susceptibility mechanisms for hip osteoarthritis:findings from a genome-wide association study meta-analysis of minimum joint space width and Mendelian randomisation cluster analyses

Author

Faber, Benjamin G., Frysz, Monika, Boer, Cindy G., Evans, Daniel S., Ebsim, Raja, Flynn, Kaitlyn A., Lundberg, Mischa, Southam, Lorraine, Hartley, April, Saunders, Fiona R., Lindner, Claudia, Gregory, Jennifer S., Aspden, Richard M., Lane, Nancy E., Harvey, Nicholas C., Evans, David M., Zeggini, Eleftheria, Davey Smith, George, Cootes, Timothy, Van Meurs, Joyce, Kemp, John P., Tobias, Jonathan H., Faber, Benjamin G., Frysz, Monika, Boer, Cindy G., Evans, Daniel S., Ebsim, Raja, Flynn, Kaitlyn A., Lundberg, Mischa, Southam, Lorraine, Hartley, April, Saunders, Fiona R., Lindner, Claudia, Gregory, Jennifer S., Aspden, Richard M., Lane, Nancy E., Harvey, Nicholas C., Evans, David M., Zeggini, Eleftheria, Davey Smith, George, Cootes, Timothy, Van Meurs, Joyce, Kemp, John P., and Tobias, Jonathan H.

Abstract

Background: Hip minimum joint space width (mJSW) provides a proxy for cartilage thickness. This study aimed to conduct a genome-wide association study (GWAS) of mJSW to (i) identify new genetic determinants of mJSW and (ii) identify which mJSW loci convey hip osteoarthritis (HOA) risk and would therefore be of therapeutic interest. Methods: GWAS meta-analysis of hip mJSW derived from plain X-rays and DXA was performed, stratified by sex and adjusted for age and ancestry principal components. Mendelian randomisation (MR) and cluster analyses were used to examine causal effect of mJSW on HOA. Findings: 50,745 individuals were included in the meta-analysis. 42 SNPs, which mapped to 39 loci, were identified. Mendelian randomisation (MR) revealed little evidence of a causal effect of mJSW on HOA (ORIVW 0.98 [95% CI 0.82–1.18]). However, MR-Clust analysis suggested the null MR estimates reflected the net effect of two distinct causal mechanisms cancelling each other out, one of which was protective, whereas the other increased HOA susceptibility. For the latter mechanism, all loci were positively associated with height, suggesting mechanisms leading to greater height and mJSW increase the risk of HOA in later life. Interpretations: One group of mJSW loci reduce HOA risk via increased mJSW, suggesting possible utility as targets for chondroprotective therapies. The second group of mJSW loci increased HOA risk, despite increasing mJSW, but were also positively related to height, suggesting they contribute to HOA risk via a growth-related mechanism. Funding: Primarily funded by the Medical Research Council and Wellcome Trust.

Published
2023

31. Lowering of circulating sclerostin may increase risk of atherosclerosis and its risk factors: evidence from a genome-wide association meta-analysis followed by Mendelian randomization

Author

CDL Onderzoek Pasterkamp, Circulatory Health, Onderzoek Precision medicine, Zheng, Jie, Wheeler, Eleanor, Pietzner, Maik, Andlauer, Till F M, Yau, Michelle S, Hartley, April E, Brumpton, Ben Michael, Rasheed, Humaira, Kemp, John P, Frysz, Monika, Robinson, Jamie, Reppe, Sjur, Prijatelj, Vid, Gautvik, Kaare M, Falk, Louise, Maerz, Winfried, Gergei, Ingrid, Peyser, Patricia A, Kavousi, Maryam, de Vries, Paul S, Miller, Clint L, Bos, Maxime, van der Laan, Sander W, Malhotra, Rajeev, Herrmann, Markus, Scharnagl, Hubert, Kleber, Marcus, Dedoussis, George, Zeggini, Eleftheria, Nethander, Maria, Ohlsson, Claes, Lorentzon, Mattias, Wareham, Nick, Langenberg, Claudia, Holmes, Michael V, Smith, George Davey, Tobias, Jonathan H, CDL Onderzoek Pasterkamp, Circulatory Health, Onderzoek Precision medicine, Zheng, Jie, Wheeler, Eleanor, Pietzner, Maik, Andlauer, Till F M, Yau, Michelle S, Hartley, April E, Brumpton, Ben Michael, Rasheed, Humaira, Kemp, John P, Frysz, Monika, Robinson, Jamie, Reppe, Sjur, Prijatelj, Vid, Gautvik, Kaare M, Falk, Louise, Maerz, Winfried, Gergei, Ingrid, Peyser, Patricia A, Kavousi, Maryam, de Vries, Paul S, Miller, Clint L, Bos, Maxime, van der Laan, Sander W, Malhotra, Rajeev, Herrmann, Markus, Scharnagl, Hubert, Kleber, Marcus, Dedoussis, George, Zeggini, Eleftheria, Nethander, Maria, Ohlsson, Claes, Lorentzon, Mattias, Wareham, Nick, Langenberg, Claudia, Holmes, Michael V, Smith, George Davey, and Tobias, Jonathan H

Published
2023

32. A Genome‐Wide Association Study Meta‐Analysis of Alpha Angle Suggests Cam‐Type Morphology May Be a Specific Feature of Hip Osteoarthritis in Older Adults

Author

Faber, Benjamin G., primary, Frysz, Monika, additional, Hartley, April E., additional, Ebsim, Raja, additional, Boer, Cindy G., additional, Saunders, Fiona R., additional, Gregory, Jennifer S., additional, Aspden, Richard M., additional, Harvey, Nicholas C., additional, Southam, Lorraine, additional, Giles, William, additional, Le Maitre, Christine L., additional, Wilkinson, J. Mark, additional, van Meurs, Joyce B. J., additional, Zeggini, Eleftheria, additional, Cootes, Timothy, additional, Lindner, Claudia, additional, Kemp, John P., additional, Davey Smith, George, additional, and Tobias, Jonathan H., additional

Published
2023
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33. Data from Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies

Author

Knipe, Duleeka W., primary, Evans, David M., primary, Kemp, John P., primary, Eeles, Rosalind, primary, Easton, Douglas F., primary, Kote-Jarai, Zsofia, primary, Al Olama, Ali Amin, primary, Benlloch, Sara, primary, Donovan, Jenny L., primary, Hamdy, Freddie C., primary, Neal, David E., primary, Davey Smith, George, primary, Lathrop, Mark, primary, and Martin, Richard M., primary

Published
2023
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34. Supplementary Tables 1 through 4 and Supplementary Figures 1 through 3 from Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies

Author

Knipe, Duleeka W., primary, Evans, David M., primary, Kemp, John P., primary, Eeles, Rosalind, primary, Easton, Douglas F., primary, Kote-Jarai, Zsofia, primary, Al Olama, Ali Amin, primary, Benlloch, Sara, primary, Donovan, Jenny L., primary, Hamdy, Freddie C., primary, Neal, David E., primary, Davey Smith, George, primary, Lathrop, Mark, primary, and Martin, Richard M., primary

Published
2023
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35. Supplementary Table 1 from Using Genetic Proxies for Lifecourse Sun Exposure to Assess the Causal Relationship of Sun Exposure with Circulating Vitamin D and Prostate Cancer Risk

Author

Bonilla, Carolina, primary, Gilbert, Rebecca, primary, Kemp, John P., primary, Timpson, Nicholas J., primary, Evans, David M., primary, Donovan, Jenny L., primary, Hamdy, Freddie C., primary, Neal, David E., primary, Fraser, William D., primary, Davey, Smith George, primary, Lewis, Sarah J., primary, Lathrop, Mark, primary, and Martin, Richard M., primary

Published
2023
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36. Data from Using Genetic Proxies for Lifecourse Sun Exposure to Assess the Causal Relationship of Sun Exposure with Circulating Vitamin D and Prostate Cancer Risk

Author

Bonilla, Carolina, primary, Gilbert, Rebecca, primary, Kemp, John P., primary, Timpson, Nicholas J., primary, Evans, David M., primary, Donovan, Jenny L., primary, Hamdy, Freddie C., primary, Neal, David E., primary, Fraser, William D., primary, Davey, Smith George, primary, Lewis, Sarah J., primary, Lathrop, Mark, primary, and Martin, Richard M., primary

Published
2023
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37. Supplementary Table 2 from Using Genetic Proxies for Lifecourse Sun Exposure to Assess the Causal Relationship of Sun Exposure with Circulating Vitamin D and Prostate Cancer Risk

Author

Bonilla, Carolina, primary, Gilbert, Rebecca, primary, Kemp, John P., primary, Timpson, Nicholas J., primary, Evans, David M., primary, Donovan, Jenny L., primary, Hamdy, Freddie C., primary, Neal, David E., primary, Fraser, William D., primary, Davey, Smith George, primary, Lewis, Sarah J., primary, Lathrop, Mark, primary, and Martin, Richard M., primary

Published
2023
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38. Supplementary Table 3 from Using Genetic Proxies for Lifecourse Sun Exposure to Assess the Causal Relationship of Sun Exposure with Circulating Vitamin D and Prostate Cancer Risk

Author

Bonilla, Carolina, primary, Gilbert, Rebecca, primary, Kemp, John P., primary, Timpson, Nicholas J., primary, Evans, David M., primary, Donovan, Jenny L., primary, Hamdy, Freddie C., primary, Neal, David E., primary, Fraser, William D., primary, Davey, Smith George, primary, Lewis, Sarah J., primary, Lathrop, Mark, primary, and Martin, Richard M., primary

Published
2023
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39. Hip joint space width is causally related to hip osteoarthritis risk via distinct protective and susceptibility mechanisms: findings from a genome-wide association study meta-analysis

Author

Frysz, Monika, primary, Faber, Benjamin G., additional, Boer, Cindy G., additional, Evans, Daniel S., additional, Ebsim, Raja, additional, Flynn, Kaitlyn A., additional, Lundberg, Mischa, additional, Southam, Lorraine, additional, Hartley, April, additional, Saunders, Fiona R., additional, Lindner, Claudia, additional, Gregory, Jennifer S., additional, Aspden, Richard M., additional, Lane, Nancy E., additional, Harvey, Nicholas C., additional, Evans, David M., additional, Zeggini, Eleftheria, additional, Smith, George Davey, additional, Cootes, Timothy, additional, Van Meurs, Joyce, additional, Kemp, John P., additional, and Tobias, Jonathan H., additional

Published
2023
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40. Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis

Author

Kemp, John P, Morris, John A, Medina-Gomez, Carolina, Forgetta, Vincenzo, Warrington, Nicole M, Youlten, Scott E, Zheng, Jie, Gregson, Celia L, Grundberg, Elin, Trajanoska, Katerina, Logan, John G, Pollard, Andrea S, Sparkes, Penny C, Ghirardello, Elena J, Allen, Rebecca, Leitch, Victoria D, Butterfield, Natalie C, Komla-Ebri, Davide, Adoum, Anne-Tounsia, Curry, Katharine F, White, Jacqueline K, Kussy, Fiona, Greenlaw, Keelin M, Xu, Changjiang, Harvey, Nicholas C, Cooper, Cyrus, Adams, David J, Greenwood, Celia M T, Maurano, Matthew T, Kaptoge, Stephen, Rivadeneira, Fernando, Tobias, Jonathan H, Croucher, Peter I, Ackert-Bicknell, Cheryl L, Bassett, J H Duncan, Williams, Graham R, Richards, J Brent, and Evans, David M

Published
2017
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41. Variants in the fetal genome near FLT1 are associated with risk of preeclampsia

Author

McGinnis, Ralph, Steinthorsdottir, Valgerdur, Williams, Nicholas O, Thorleifsson, Gudmar, Shooter, Scott, Hjartardottir, Sigrun, Bumpstead, Suzannah, Stefansdottir, Lilja, Hildyard, Lucy, Sigurdsson, Jon K, Kemp, John P, Silva, Gabriela B, Thomsen, Liv Cecilie V, Jääskeläinen, Tiina, Kajantie, Eero, Chappell, Sally, Kalsheker, Noor, Moffett, Ashley, Hiby, Susan, Lee, Wai Kwong, Padmanabhan, Sandosh, Simpson, Nigel A B, Dolby, Vivien A, Staines-Urias, Eleonora, Engel, Stephanie M, Haugan, Anita, Trogstad, Lill, Svyatova, Gulnara, Zakhidova, Nodira, Najmutdinova, Dilbar, Dominiczak, Anna F, Gjessing, Håkon K, Casas, Juan P, Dudbridge, Frank, Walker, James J, Pipkin, Fiona Broughton, Thorsteinsdottir, Unnur, Geirsson, Reynir T, Lawlor, Debbie A, Iversen, Ann-Charlotte, Magnus, Per, Laivuori, Hannele, Stefansson, Kari, and Morgan, Linda

Published
2017
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42. The effects of height and BMI on prostate cancer incidence and mortality: a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Author

PRACTICAL consortium, Davies, Neil M., Gaunt, Tom R., Lewis, Sarah J., Holly, Jeff, Donovan, Jenny L., Hamdy, Freddie C., Kemp, John P., Eeles, Rosalind, Easton, Doug, Kote-Jarai, Zsofia, Olama, Ali Amin Al, Benlloch, Sara, Muir, Kenneth, Giles, Graham G., Wiklund, Fredrik, Gronberg, Henrik, Haiman, Christopher A., Schleutker, Johanna, Nordestgaard, Børge G., Travis, Ruth C., Neal, David, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L., Blot, William J., Thibodeau, Stephen, Maier, Christiane, Kibel, Adam S., Cybulski, Cezary, Cannon-Albright, Lisa, Brenner, Hermann, Park, Jong, Kaneva, Radka, Batra, Jyotsna, Teixeira, Manuel R., Pandha, Hardev, Lathrop, Mark, Smith, George Davey, and Martin, Richard M.

Published
2015

43. Development of a polygenic risk score to improve screening for fracture risk: A genetic risk prediction study

Author

Forgetta, Vincenzo, Keller-Baruch, Julyan, Forest, Marie, Durand, Audrey, Bhatnagar, Sahir, Kemp, John P., Nethander, Maria, Evans, Daniel, Morris, John A., Kiel, Douglas P., Rivadeneira, Fernando, Johansson, Helena, Harvey, Nicholas C., Mellström, Dan, Karlsson, Magnus, Cooper, Cyrus, Evans, David M., Clarke, Robert, Kanis, John A., Orwoll, Eric, McCloskey, Eugene V., Ohlsson, Claes, Pineau, Joelle, Leslie, William D., Greenwood, Celia M. T., Richards, J. Brent, Gaynor-Brook, Louise, and Turner, Richard

Subjects
Genetic aspects, Health screening, Osteoporosis -- Genetic aspects, Bone density -- Genetic aspects, Fractures (Injuries) -- Genetic aspects, Genomics -- Genetic aspects
Abstract

Author(s): Vincenzo Forgetta 1, Julyan Keller-Baruch 2, Marie Forest 1, Audrey Durand 3, Sahir Bhatnagar 1, John P. Kemp 4,5, Maria Nethander 6,7, Daniel Evans 8, John A. Morris 1, [...], Background Since screening programs identify only a small proportion of the population as eligible for an intervention, genomic prediction of heritable risk factors could decrease the number needing to be screened by removing individuals at low genetic risk. We therefore tested whether a polygenic risk score for heel quantitative ultrasound speed of sound (SOS)-a heritable risk factor for osteoporotic fracture-can identify low-risk individuals who can safely be excluded from a fracture risk screening program. Methods and findings A polygenic risk score for SOS was trained and selected in 2 separate subsets of UK Biobank (comprising 341,449 and 5,335 individuals). The top-performing prediction model was termed 'gSOS', and its utility in fracture risk screening was tested in 5 validation cohorts using the National Osteoporosis Guideline Group clinical guidelines (N = 10,522 eligible participants). All individuals were genome-wide genotyped and had measured fracture risk factors. Across the 5 cohorts, the average age ranged from 57 to 75 years, and 54% of studied individuals were women. The main outcomes were the sensitivity and specificity to correctly identify individuals requiring treatment with and without genetic prescreening. The reference standard was a bone mineral density (BMD)-based Fracture Risk Assessment Tool (FRAX) score. The secondary outcomes were the proportions of the screened population requiring clinical-risk-factor-based FRAX (CRF-FRAX) screening and BMD-based FRAX (BMD-FRAX) screening. gSOS was strongly correlated with measured SOS (r.sup.2 = 23.2%, 95% CI 22.7% to 23.7%). Without genetic prescreening, guideline recommendations achieved a sensitivity and specificity for correct treatment assignment of 99.6% and 97.1%, respectively, in the validation cohorts. However, 81% of the population required CRF-FRAX tests, and 37% required BMD-FRAX tests to achieve this accuracy. Using gSOS in prescreening and limiting further assessment to those with a low gSOS resulted in small changes to the sensitivity and specificity (93.4% and 98.5%, respectively), but the proportions of individuals requiring CRF-FRAX tests and BMD-FRAX tests were reduced by 37% and 41%, respectively. Study limitations include a reliance on cohorts of predominantly European ethnicity and use of a proxy of fracture risk. Conclusions Our results suggest that the use of a polygenic risk score in fracture risk screening could decrease the number of individuals requiring screening tests, including BMD measurement, while maintaining a high sensitivity and specificity to identify individuals who should be recommended an intervention.

Published
2020
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44. A GWAS meta-analysis of alpha angle suggests cam-type morphology may be a specific feature of hip osteoarthritis in older adults

Author

Faber, Benjamin G., Frysz, Monika, Hartley, April E., Ebsim, Raja, Boer, Cindy G., Saunders, Fiona R., Gregory, Jennifer S., Aspden, Richard M., Harvey, Nicholas C., Southam, Lorraine, Giles, William, Le Maitre, Christine L., Wilkinson, J. Mark, van Meurs, Joyce B.J., Zeggini, Eleftheria, Cootes, Timothy, Lindner, Claudia, Kemp, John P., Davey Smith, George, and Tobias, Jonathan H.

Abstract

Objectives: To examine the genetic architecture of cam morphology, using alpha angle (AA) as a proxy measure, we conducted an AA genome wide association study (GWAS), followed by Mendelian randomisation (MR) to evaluate its causal relationship with hip osteoarthritis (HOA).Methods: Observational analyses examined associations between AA derived from hip DXA scans in UK Biobank (UKB), and radiographic HOA (rHOA) and subsequent total hip replacement (THR). Afterwards, an AA GWAS meta-analysis was performed (n=44,214), using AA previously derived in the Rotterdam Study (RS). Linkage disequilibrium score regression assessed the genetic correlation between AA and HOA. Genetic associations with PResults: DXA-derived AA showed expected associations between AA and rHOA (OR 1.63 [95% CI 1.58-1.67]) and THR (HR 1.45 [1.33-1.59]) in UKB. The heritability of AA was 10% and AA had a moderate genetic correlation with HOA (rg =0.26 [0.10-0.43]). Eight independent genetic signals were associated with AA. Two-sample MR provided weak evidence of causal effects of AA on HOA risk (inverse variance weighted (IVW): OR=1.84 [1.14-2.96], P 0.01). In contrast, genetic predisposition for HOA had stronger evidence of a causal effect on increased AA (IVW: β=0.09 [0.04-0.13], P 4.58 x 10-05 ).Conclusions: Expected observational associations between AA and related clinical outcomes provided face-validity for the DXA-derived AA measures. Evidence of bidirectional associations between AA and HOA, particularly in the reverse direction, suggests that hip shape modelling secondary to a genetic predisposition to HOA contributes to the well-established relationship between HOA and cam morphology in older adults.

Published
2023

45. Fraction of exhaled nitric oxide values in childhood are associated with 17q11.2-q12 and 17q12-q21 variants

Author

van der Valk, Ralf J.P., Duijts, Liesbeth, Timpson, Nicolas J., Salam, Muhammad T., Standl, Marie, Curtin, John A., Genuneit, Jon, Kerhof, Marjan, Kreiner-Møller, Eskil, Cáceres, Alejandro, Gref, Anna, Liang, Liming L., Taal, H. Rob, Bouzigon, Emmanuelle, Demenais, Florence, Nadif, Rachel, Ober, Carole, Thompson, Emma E., Estrada, Karol, Hofman, Albert, Uitterlinden, André G., van Duijn, Cornélia, Rivadeneira, Fernando, Li, Xia, Eckel, Sandrah P., Berhane, Kiros, Gauderman, W. James, Granell, Raquel, Evans, David M., St Pourcain, Beate, McArdle, Wendy, Kemp, John P., Smith, George Davey, Tiesler, Carla M.T., Flexeder, Claudia, Simpson, Angela, Murray, Clare S., Fuchs, Oliver, Postma, Dirkje S., Bønnelykke, Klaus, Torrent, Maties, Andersson, Martin, Sleiman, Patrick, Hakonarson, Hakon, Cookson, William O., Moffatt, Miriam F., Paternoster, Lavinia, Melén, Erik, Sunyer, Jordi, Bisgaard, Hans, Koppelman, Gerard H., Ege, Markus, Custovic, Adnan, Heinrich, Joachim, Gilliland, Frank D., Henderson, Alexander J., Jaddoe, Vincent W.V., and de Jongste, Johan C.

Published
2014
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47. Nine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error

Author

Reinhart, William, Belin, Michael W., Schultze, Robert L., Morason, Todd, Sugar, Alan, Mian, Shahzad, Soong, Hunson Kaz, Colby, Kathryn, Jurkunas, Ula, Yee, Richard, Vital, Mark, Alfonso, Eduardo, Karp, Carol, Lee, Yunhee, Yoo, Sonia, Hammersmith, Kristin, Cohen, Elisabeth, Laibson, Peter, Rapuano, Christopher, Ayres, Brandon, Croasdale, Christopher, Caudill, James, Patel, Sanjay, Baratz, Keith, Bourne, William, Maguire, Leo, Sugar, Joel, Tu, Elmer, Djalilian, Ali, Mootha, Vinod, McCulley, James, Bowman, Wayne, Cavanaugh, H. Dwight, Verity, Steven, Verdier, David, Renucci, Ann, Oliva, Matt, Rotkis, Walter, Hardten, David R., Fahmy, Ahmad, Brown, Marlene, Reeves, Sherman, Davis, Elizabeth A., Lindstrom, Richard, Hauswirth, Scott, Hamilton, Stephen, Lee, W. Barry, Price, Francis, Price, Marianne, Kelly, Kathleen, Peters, Faye, Shaughnessy, Michael, Steinemann, Thomas, Dupps, B.J., Meisler, David M., Mifflin, Mark, Olson, Randal, Aldave, Anthony, Holland, Gary, Mondino, Bartly J., Rosenwasser, George, Gorovoy, Mark, Dunn, Steven P., Heidemann, David G., Terry, Mark, Shamie, Neda, Rosenfeld, Steven I., Suedekum, Brandon, Hwang, David, Stone, Donald, Chodosh, James, Galentine, Paul G., Bardenstein, David, Goddard, Katrina, Chin, Hemin, Mannis, Mark, Varma, Rohit, Borecki, Ingrid, Cheng, Ching-Yu, Schache, Maria, Ikram, M. Kamran, Young, Terri L., Guggenheim, Jeremy A., Vitart, Veronique, MacGregor, Stuart, Verhoeven, Virginie J.M., Barathi, Veluchamy A., Liao, Jiemin, Hysi, Pirro G., Bailey-Wilson, Joan E., St. Pourcain, Beate, Kemp, John P., McMahon, George, Timpson, Nicholas J., Evans, David M., Montgomery, Grant W., Mishra, Aniket, Wang, Ya Xing, Wang, Jie Jin, Rochtchina, Elena, Polasek, Ozren, Wright, Alan F., Amin, Najaf, van Leeuwen, Elisabeth M., Wilson, James F., Pennell, Craig E., van Duijn, Cornelia M., de Jong, Paulus T.V.M., Vingerling, Johannes R., Zhou, Xin, Chen, Peng, Li, Ruoying, Tay, Wan-Ting, Zheng, Yingfeng, Chew, Merwyn, Burdon, Kathryn P., Craig, Jamie E., Iyengar, Sudha K., Igo, Robert P., Jr., Lass, Jonathan H., Jr., Chew, Emily Y., Haller, Toomas, Mihailov, Evelin, Metspalu, Andres, Wedenoja, Juho, Simpson, Claire L., Wojciechowski, Robert, Höhn, René, Mirshahi, Alireza, Zeller, Tanja, Pfeiffer, Norbert, Lackner, Karl J., Bettecken, Thomas, Meitinger, Thomas, Oexle, Konrad, Pirastu, Mario, Portas, Laura, Nag, Abhishek, Williams, Katie M., Yonova-Doing, Ekaterina, Klein, Ronald, Klein, Barbara E., Hosseini, S. Mohsen, Paterson, Andrew D., Makela, Kari-Matti, Lehtimaki, Terho, Kahonen, Mika, Raitakari, Olli, Yoshimura, Nagahisa, Matsuda, Fumihiko, Chen, Li Jia, Pang, Chi Pui, Yip, Shea Ping, Yap, Maurice K.H., Meguro, Akira, Mizuki, Nobuhisa, Inoko, Hidetoshi, Foster, Paul J., Zhao, Jing Hua, Vithana, Eranga, Tai, E-Shyong, Fan, Qiao, Xu, Liang, Campbell, Harry, Fleck, Brian, Rudan, Igor, Aung, Tin, Hofman, Albert, Uitterlinden, André G., Bencic, Goran, Khor, Chiea-Chuen, Forward, Hannah, Pärssinen, Olavi, Mitchell, Paul, Rivadeneira, Fernando, Hewitt, Alex W., Williams, Cathy, Oostra, Ben A., Teo, Yik-Ying, Hammond, Christopher J., Stambolian, Dwight, Mackey, David A., Klaver, Caroline C.W., Wong, Tien-Yin, Saw, Seang-Mei, and Baird, Paul N.

Published
2013
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50. Evaluation of shared genetic aetiology between osteoarthritis and bone mineral density identifies SMAD3 as a novel osteoarthritis risk locus

Author

Hackinger, Sophie, Trajanoska, Katerina, Styrkarsdottir, Unnur, Zengini, Eleni, Steinberg, Julia, Ritchie, Graham R.S., Hatzikotoulas, Konstantinos, Gilly, Arthur, Evangelou, Evangelos, Kemp, John P., Evans, David, Ingvarsson, Thorvaldur, Jonsson, Helgi, Thorsteinsdottir, Unnur, Stefansson, Kari, McCaskie, Andrew W., Brooks, Roger A., Wilkinson, Jeremy M., Rivadeneira, Fernando, and Zeggini, Eleftheria

Published
2017
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