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1. Genetic association study of childhood aggression across raters, instruments, and age.

Author

Ip, Hill, van der Laan, Camiel, Krapohl, Eva, Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja, St Pourcain, Beate, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Colodro-Conde, Lucía, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol, Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke, Adkins, Daniel, Border, Richard, Peterson, Roseann, Prinz, Joseph, Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer, Day, Felix, Hottenga, Jouke-Jan, Allegrini, Andrea, Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Soler Artigas, María, Rovira, Paula, Bosch, Rosa, Español, Gemma, Ramos Quiroga, Josep, Neumann, Alexander, Ensink, Judith, Grasby, Katrina, Morosoli, José, Tong, Xiaoran, Marrington, Shelby, Middeldorp, Christel, Scott, James, Vinkhuyzen, Anna, Shabalin, Andrey, Corley, Robin, Evans, Luke, Sugden, Karen, Alemany, Silvia, Sass, Lærke, Vinding, Rebecca, Ruth, Kate, Tyrrell, Jess, Davies, Gareth, Ehli, Erik, Hagenbeek, Fiona, De Zeeuw, Eveline, Van Beijsterveldt, Toos, Larsson, Henrik, Snieder, Harold, Verhulst, Frank, Amin, Najaf, Whipp, Alyce, Korhonen, Tellervo, Vuoksimaa, Eero, Rose, Richard, Uitterlinden, André, Heath, Andrew, Madden, Pamela, Haavik, Jan, Harris, Jennifer, Helgeland, Øyvind, Johansson, Stefan, Knudsen, Gun, Njolstad, Pal, Lu, Qing, Rodriguez, Alina, Henders, Anjali, Mamun, Abdullah, Najman, Jackob, Brown, Sandy, Hopfer, Christian, Krauter, Kenneth, Reynolds, Chandra, Smolen, Andrew, Stallings, Michael, Wadsworth, Sally, Wall, Tamara, Silberg, Judy, Miller, Allison, Keltikangas-Järvinen, Liisa, Hakulinen, Christian, Pulkki-Råback, Laura, Havdahl, Alexandra, Magnus, Per, and Raitakari, Olli

Subjects
Adolescent, Aggression, Child, Child, Preschool, Female, Genetic Association Studies, Genome-Wide Association Study, Humans, Infant, Mental Disorders, Retrospective Studies
Abstract

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from rg = 0.46 between self- and teacher-assessment to rg = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

Published
2021

2. A meta-analysis of genome-wide association studies identifies multiple longevity genes.

Author

Deelen, Joris, Evans, Daniel S, Arking, Dan E, Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K, Biggs, Mary L, van der Spek, Ashley, Atzmon, Gil, Ware, Erin B, Sarnowski, Chloé, Smith, Albert V, Seppälä, Ilkka, Cordell, Heather J, Dose, Janina, Amin, Najaf, Arnold, Alice M, Ayers, Kristin L, Barzilai, Nir, Becker, Elizabeth J, Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C, Cubaynes, Sarah, Cummings, Steven R, Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D, Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B, Huisman, Martijn, Hurme, Mikko A, Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon LR, Kingston, Andrew, Kirkwood, Thomas BL, Launer, Lenore J, Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B, Nie, Chao, Nohr, Ellen A, Orwoll, Eric S, Perls, Thomas T, Province, Michael A, Psaty, Bruce M, Raitakari, Olli T, Reinders, Marcel JT, Robine, Jean-Marie, Rotter, Jerome I, Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild IA, Taylor, Kent D, Uitterlinden, André G, van der Flier, Wiesje, van der Lee, Sven J, van Duijn, Cornelia M, van Heemst, Diana, Vaupel, James W, Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P, Lunetta, Kathryn L, Slagboom, P Eline, and Murabito, Joanne M

Subjects
Humans, Heat-Shock Proteins, Longevity, Apolipoprotein E2, Apolipoprotein E4, Genome-Wide Association Study
Abstract

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Published
2019

3. Genetic and environmental perturbations lead to regulatory decoherence

Author

Lea, Amanda, Subramaniam, Meena, Ko, Arthur, Lehtimäki, Terho, Raitoharju, Emma, Kähönen, Mika, Seppälä, Ilkka, Mononen, Nina, Raitakari, Olli T, Ala-Korpela, Mika, Pajukanta, Päivi, Zaitlen, Noah, and Ayroles, Julien F

Subjects
Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Computer Simulation, Environmental Exposure, Gene Expression Profiling, Genetic Variation, Humans, Individuality, Magnetic Resonance Spectroscopy, Metabolic Diseases, Metabolome, Quantitative Trait Loci, co-expression, decanalization, decoherence, genetics, genomics, human, human biology, medicine, metabolic syndrome, Biochemistry and Cell Biology
Abstract

Correlation among traits is a fundamental feature of biological systems that remains difficult to study. To address this problem, we developed a flexible approach that allows us to identify factors associated with inter-individual variation in correlation. We use data from three human cohorts to study the effects of genetic and environmental variation on correlations among mRNA transcripts and among NMR metabolites. We first show that environmental exposures (infection and disease) lead to a systematic loss of correlation, which we define as 'decoherence'. Using longitudinal data, we show that decoherent metabolites are better predictors of whether someone will develop metabolic syndrome than metabolites commonly used as biomarkers of this disease. Finally, we demonstrate that correlation itself is under genetic control by mapping hundreds of 'correlation quantitative trait loci (QTLs)'. Together, this work furthers our understanding of how and why coordinated biological processes break down, and points to a potential role for decoherence in disease.Editorial noteThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).

Published
2019

4. Genome‐Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Author

Smith, Caren E, Follis, Jack L, Dashti, Hassan S, Tanaka, Toshiko, Graff, Mariaelisa, Fretts, Amanda M, Kilpeläinen, Tuomas O, Wojczynski, Mary K, Richardson, Kris, Nalls, Mike A, Schulz, Christina‐Alexandra, Liu, Yongmei, Frazier‐Wood, Alexis C, van Eekelen, Esther, Wang, Carol, de Vries, Paul S, Mikkilä, Vera, Rohde, Rebecca, Psaty, Bruce M, Hansen, Torben, Feitosa, Mary F, Lai, Chao‐Qiang, Houston, Denise K, Ferruci, Luigi, Ericson, Ulrika, Wang, Zhe, de Mutsert, Renée, Oddy, Wendy H, de Jonge, Ester AL, Seppälä, Ilkka, Justice, Anne E, Lemaitre, Rozenn N, Sørensen, Thorkild IA, Province, Michael A, Parnell, Laurence D, Garcia, Melissa E, Bandinelli, Stefania, Orho‐Melander, Marju, Rich, Stephen S, Rosendaal, Frits R, Pennell, Craig E, Jong, Jessica C Kiefte‐de, Kähönen, Mika, Young, Kristin L, Pedersen, Oluf, Aslibekyan, Stella, Rotter, Jerome I, Mook‐Kanamori, Dennis O, Zillikens, M Carola, Raitakari, Olli T, North, Kari E, Overvad, Kim, Arnett, Donna K, Hofman, Albert, Lehtimäki, Terho, Tjønneland, Anne, Uitterlinden, André G, Rivadeneira, Fernando, Franco, Oscar H, German, J Bruce, Siscovick, David S, Cupples, L Adrienne, and Ordovás, José M

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Genetics, Prevention, Nutrition, Obesity, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Cancer, Metabolic and endocrine, Actins, Adult, Aged, Body Mass Index, Cohort Studies, Cross-Sectional Studies, Dairy Products, Female, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Myosin-Light-Chain Phosphatase, Polymorphism, Single Nucleotide, White People, body mass index, CHARGE consortium, dairy intake, genome-wide interaction study, meta-analysis, Food Sciences, Public Health and Health Services, Food Science, Nutrition & Dietetics, Food sciences, Nutrition and dietetics
Abstract

ScopeBody weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption.Methods and resultsA genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction

Published
2018

5. Three genetic–environmental networks for human personality

Author

Zwir, Igor, Del-Val, Coral, Arnedo, Javier, Pulkki-Råback, Laura, Konte, Bettina, Yang, Sarah S., Romero-Zaliz, Rocio, Hintsanen, Mirka, Cloninger, Kevin M., Garcia, Danilo, Svrakic, Dragan M., Lester, Nigel, Rozsa, Sandor, Mesa, Alberto, Lyytikäinen, Leo-Pekka, Giegling, Ina, Kähönen, Mika, Martinez, Maribel, Seppälä, Ilkka, Raitoharju, Emma, de Erausquin, Gabriel A., Mamah, Daniel, Raitakari, Olli, Rujescu, Dan, Postolache, Teodor T., Gu, C. Charles, Sung, Joohon, Lehtimäki, Terho, Keltikangas-Järvinen, Liisa, and Cloninger, C. Robert

Published
2021
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6. 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, Genetics, Human Genome, 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

7. Integrative approaches for large-scale transcriptome-wide association studies

Author

Gusev, Alexander, Ko, Arthur, Shi, Huwenbo, Bhatia, Gaurav, Chung, Wonil, Penninx, Brenda WJH, Jansen, Rick, de Geus, Eco JC, Boomsma, Dorret I, Wright, Fred A, Sullivan, Patrick F, Nikkola, Elina, Alvarez, Marcus, Civelek, Mete, Lusis, Aldons J, Lehtimäki, Terho, Raitoharju, Emma, Kähönen, Mika, Seppälä, Ilkka, Raitakari, Olli T, Kuusisto, Johanna, Laakso, Markku, Price, Alkes L, Pajukanta, Päivi, and Pasaniuc, Bogdan

Subjects
Biological Sciences, Genetics, Obesity, Human Genome, Cancer, Generic health relevance, Animals, Gene Expression Regulation, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Mice, Phenotype, Quantitative Trait Loci, Transcriptome, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ∼ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.

Published
2016

8. Uncovering the complex genetics of human temperament

Author

Zwir, Igor, Arnedo, Javier, Del-Val, Coral, Pulkki-Råback, Laura, Konte, Bettina, Yang, Sarah S., Romero-Zaliz, Rocio, Hintsanen, Mirka, Cloninger, Kevin M., Garcia, Danilo, Svrakic, Dragan M., Rozsa, Sandor, Martinez, Maribel, Lyytikäinen, Leo-Pekka, Giegling, Ina, Kähönen, Mika, Hernandez-Cuervo, Helena, Seppälä, Ilkka, Raitoharju, Emma, de Erausquin, Gabriel A., Raitakari, Olli, Rujescu, Dan, Postolache, Teodor T., Sung, Joohon, Keltikangas-Järvinen, Liisa, Lehtimäki, Terho, and Cloninger, C. Robert

Published
2020
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9. Uncovering the complex genetics of human character

Author

Zwir, Igor, Arnedo, Javier, Del-Val, Coral, Pulkki-Råback, Laura, Konte, Bettina, Yang, Sarah S., Romero-Zaliz, Rocio, Hintsanen, Mirka, Cloninger, Kevin M., Garcia, Danilo, Svrakic, Dragan M., Rozsa, Sandor, Martinez, Maribel, Lyytikäinen, Leo-Pekka, Giegling, Ina, Kähönen, Mika, Hernandez-Cuervo, Helena, Seppälä, Ilkka, Raitoharju, Emma, de Erausquin, Gabriel A., Raitakari, Olli, Rujescu, Dan, Postolache, Teodor T., Sung, Joohon, Keltikangas-Järvinen, Liisa, Lehtimäki, Terho, and Cloninger, C. Robert

Published
2020
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10. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians 1 , 2

Author

Fretts, Amanda M, Follis, Jack L, Nettleton, Jennifer A, Lemaitre, Rozenn N, Ngwa, Julius S, Wojczynski, Mary K, Kalafati, Ioanna Panagiota, Varga, Tibor V, Frazier-Wood, Alexis C, Houston, Denise K, Lahti, Jari, Ericson, Ulrika, van den Hooven, Edith H, Mikkilä, Vera, Kiefte-de Jong, Jessica C, Mozaffarian, Dariush, Rice, Kenneth, Renström, Frida, North, Kari E, McKeown, Nicola M, Feitosa, Mary F, Kanoni, Stavroula, Smith, Caren E, Garcia, Melissa E, Tiainen, Anna-Maija, Sonestedt, Emily, Manichaikul, Ani, van Rooij, Frank JA, Dimitriou, Maria, Raitakari, Olli, Pankow, James S, Djoussé, Luc, Province, Michael A, Hu, Frank B, Lai, Chao-Qiang, Keller, Margaux F, Perälä, Mia-Maria, Rotter, Jerome I, Hofman, Albert, Graff, Misa, Kähönen, Mika, Mukamal, Kenneth, Johansson, Ingegerd, Ordovas, Jose M, Liu, Yongmei, Männistö, Satu, Uitterlinden, André G, Deloukas, Panos, Seppälä, Ilkka, Psaty, Bruce M, Cupples, L Adrienne, Borecki, Ingrid B, Franks, Paul W, Arnett, Donna K, Nalls, Mike A, Eriksson, Johan G, Orho-Melander, Marju, Franco, Oscar H, Lehtimäki, Terho, Dedoussis, George V, Meigs, James B, and Siscovick, David S

Subjects
Biomedical and Clinical Sciences, Nutrition and Dietetics, Prevention, Diabetes, Genetics, Aging, Cardiovascular, Nutrition, Metabolic and endocrine, Blood Glucose, Cohort Studies, Genetic Association Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hyperglycemia, Hyperinsulinism, Insulin, Insulin Resistance, Insulin Secretion, Insulin-Secreting Cells, Meat, Meat Products, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, diet, gene–diet interaction, glucose, insulin, meat intake, meta-analysis, Engineering, Medical and Health Sciences, Nutrition & Dietetics, Clinical sciences, Nutrition and dietetics
Abstract

BackgroundRecent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.ObjectiveWe investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus.DesignFourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined 1) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations.ResultsProcessed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-ln-pmol/L (95% CI: 0.035, 0.063-ln-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance.ConclusionThe association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms. Six of the participating studies are registered at clinicaltrials.gov as NCT0000513 (Atherosclerosis Risk in Communities), NCT00149435 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetics of Lipid Lowering Drugs and Diet Network), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

Published
2015

11. 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, Human Genome, Brain Disorders, Depression, Mental Health, Mental Illness, Serious Mental Illness, Major Depressive Disorder, 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

12. 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

13. Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants 2–4

Author

Dashti, Hassan S, Follis, Jack L, Smith, Caren E, Tanaka, Toshiko, Cade, Brian E, Gottlieb, Daniel J, Hruby, Adela, Jacques, Paul F, Lamon-Fava, Stefania, Richardson, Kris, Saxena, Richa, Scheer, Frank AJL, Kovanen, Leena, Bartz, Traci M, Perälä, Mia-Maria, Jonsson, Anna, Frazier-Wood, Alexis C, Kalafati, Ioanna-Panagiota, Mikkilä, Vera, Partonen, Timo, Lemaitre, Rozenn N, Lahti, Jari, Hernandez, Dena G, Toft, Ulla, Johnson, W Craig, Kanoni, Stavroula, Raitakari, Olli T, Perola, Markus, Psaty, Bruce M, Ferrucci, Luigi, Grarup, Niels, Highland, Heather M, Rallidis, Loukianos, Kähönen, Mika, Havulinna, Aki S, Siscovick, David S, Räikkönen, Katri, Jørgensen, Torben, Rotter, Jerome I, Deloukas, Panos, Viikari, Jorma SA, Mozaffarian, Dariush, Linneberg, Allan, Seppälä, Ilkka, Hansen, Torben, Salomaa, Veikko, Gharib, Sina A, Eriksson, Johan G, Bandinelli, Stefania, Pedersen, Oluf, Rich, Stephen S, Dedoussis, George, Lehtimäki, Terho, and Ordovás, José M

Subjects
Aging, Sleep Research, Obesity, Prevention, Nutrition, Genetics, Neurosciences, Behavioral and Social Science, Oral and gastrointestinal, Cardiovascular, Metabolic and endocrine, Cancer, Adult, Body Mass Index, CLOCK Proteins, Cohort Studies, Cross-Sectional Studies, Diet, Dietary Proteins, Energy Intake, Fatty Acids, Unsaturated, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Sleep, White People, Young Adult, CLOCK, circadian rhythm, dietary intake, gene-environment interaction, sleep duration, gene-environment, interaction, Engineering, Medical and Health Sciences, Nutrition & Dietetics
Abstract

BackgroundShort sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake.ObjectivesWe examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations.DesignWe conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium.ResultsWe observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 ± 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (-0.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake.ConclusionsOur results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile.

Published
2015

15. Publisher Correction: A meta-analysis of genome-wide association studies identifies multiple longevity genes

Author

Deelen, Joris, Evans, Daniel S., Arking, Dan E., Tesi, Niccolò, Nygaard, Marianne, Liu, Xiaomin, Wojczynski, Mary K., Biggs, Mary L., van der Spek, Ashley, Atzmon, Gil, Ware, Erin B., Sarnowski, Chloé, Smith, Albert V., Seppälä, Ilkka, Cordell, Heather J., Dose, Janina, Amin, Najaf, Arnold, Alice M., Ayers, Kristin L., Barzilai, Nir, Becker, Elizabeth J., Beekman, Marian, Blanché, Hélène, Christensen, Kaare, Christiansen, Lene, Collerton, Joanna C., Cubaynes, Sarah, Cummings, Steven R., Davies, Karen, Debrabant, Birgit, Deleuze, Jean-François, Duncan, Rachel, Faul, Jessica D., Franceschi, Claudio, Galan, Pilar, Gudnason, Vilmundur, Harris, Tamara B., Huisman, Martijn, Hurme, Mikko A., Jagger, Carol, Jansen, Iris, Jylhä, Marja, Kähönen, Mika, Karasik, David, Kardia, Sharon L. R., Kingston, Andrew, Kirkwood, Thomas B. L., Launer, Lenore J., Lehtimäki, Terho, Lieb, Wolfgang, Lyytikäinen, Leo-Pekka, Martin-Ruiz, Carmen, Min, Junxia, Nebel, Almut, Newman, Anne B., Nie, Chao, Nohr, Ellen A., Orwoll, Eric S., Perls, Thomas T., Province, Michael A., Psaty, Bruce M., Raitakari, Olli T., Reinders, Marcel J. T., Robine, Jean-Marie, Rotter, Jerome I., Sebastiani, Paola, Smith, Jennifer, Sørensen, Thorkild I. A., Taylor, Kent D., Uitterlinden, André G., van der Flier, Wiesje, van der Lee, Sven J., van Duijn, Cornelia M., van Heemst, Diana, Vaupel, James W., Weir, David, Ye, Kenny, Zeng, Yi, Zheng, Wanlin, Holstege, Henne, Kiel, Douglas P., Lunetta, Kathryn L., Slagboom, P. Eline, and Murabito, Joanne M.

Published
2021
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17. DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Author

Gomez-Alonso, Monica del C., Kretschmer, Anja, Wilson, Rory, Pfeiffer, Liliane, Karhunen, Ville, Seppälä, Ilkka, Zhang, Weihua, Mittelstraß, Kirstin, Wahl, Simone, Matias-Garcia, Pamela R., Prokisch, Holger, Horn, Sacha, Meitinger, Thomas, Serrano-Garcia, Luis R., Sebert, Sylvain, Raitakari, Olli, Loh, Marie, Rathmann, Wolfgang, Müller-Nurasyid, Martina, Herder, Christian, Roden, Michael, Hurme, Mikko, Jarvelin, Marjo-Riitta, Ala-Korpela, Mika, Kooner, Jaspal S., Peters, Annette, Lehtimäki, Terho, Chambers, John C., Gieger, Christian, Kettunen, Johannes, and Waldenberger, Melanie

Published
2021
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21. OTTERS:a powerful TWAS framework leveraging summary-level reference data

Author

Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., Yang, Jingjing, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Biological Psychology, Amsterdam Reproduction & Development, APH - Methodology, APH - Personalized Medicine, Internal Medicine, Tampere University, Department of Clinical Chemistry, and Clinical Medicine

Subjects
Multidisciplinary, 1182 Biochemistry, cell and molecular biology, General Physics and Astronomy, 3111 Biomedicine, General Chemistry, Medical Genetics, General Biochemistry, Genetics and Molecular Biology, Medicinsk genetik
Abstract

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies. Godkänd;2023;Nivå 0;2023-04-06 (hanlid);Funder: for more funders see the article https://doi.org/10.1038/s41467-023-36862-w

Published
2023
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22. Multi-ethnic genome-wide association study for atrial fibrillation

Author

Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Almgren, Peter, Alonso, Alvaro, Anderson, Christopher D., Aragam, Krishna G., Arking, Dan E., Barnard, John, Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Boerwinkle, Eric, Bottinger, Erwin B., Brody, Jennifer A., Calkins, Hugh, Campbell, Archie, Cappola, Thomas P., Carlquist, John, Chasman, Daniel I., Chen, Lin Y., Chen, Yii-Der Ida, Choi, Eue-Keun, Choi, Seung Hoan, Christophersen, Ingrid E., Chung, Mina K., Cole, John W., Conen, David, Cook, James, Crijns, Harry J., Cutler, Michael J., Damrauer, Scott M., Daniels, Brian R., Darbar, Dawood, Delgado, Graciela, Denny, Joshua C., Dichgans, Martin, Dörr, Marcus, Dudink, Elton A., Dudley, Samuel C., Esa, Nada, Esko, Tonu, Eskola, Markku, Fatkin, Diane, Felix, Stephan B., Ford, Ian, Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gudnason, Vilmundur, Guo, Xiuqing, Gupta, Namrata, Gustafsson, Stefan, Gutmann, Rebecca, Hamsten, Anders, Harris, Tamara B., Hayward, Caroline, Heckbert, Susan R., Hernesniemi, Jussi, Hocking, Lynne J., Hofman, Albert, Horimoto, Andrea R. V. R., Huang, Jie, Huang, Paul L., Huffman, Jennifer, Ingelsson, Erik, Ipek, Esra Gucuk, Ito, Kaoru, Jimenez-Conde, Jordi, Johnson, Renee, Jukema, J. Wouter, Kääb, Stefan, Kähönen, Mika, Kamatani, Yoichiro, Kane, John P., Kastrati, Adnan, Kathiresan, Sekar, Katschnig-Winter, Petra, Kavousi, Maryam, Kessler, Thorsten, Kietselaer, Bas L., Kirchhof, Paulus, Kleber, Marcus E., Knight, Stacey, Krieger, Jose E., Kubo, Michiaki, Launer, Lenore J., Laurikka, Jari, Lehtimäki, Terho, Leineweber, Kirsten, Lemaitre, Rozenn N., Li, Man, Lim, Hong Euy, Lin, Henry J., Lin, Honghuang, Lind, Lars, Lindgren, Cecilia M., Lokki, Marja-Liisa, London, Barry, Loos, Ruth J. F., Low, Siew-Kee, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Macfarlane, Peter W., Magnusson, Patrik K., Mahajan, Anubha, Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., Margolin, Lauren, Margulies, Kenneth B., März, Winfried, McManus, David D., Melander, Olle, Mohanty, Sanghamitra, Montgomery, Jay A., Morley, Michael P., Morris, Andrew P., Müller-Nurasyid, Martina, Natale, Andrea, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Niemeijer, Maartje N., Nikus, Kjell, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Olesen, Morten S., Orho-Melander, Marju, Padmanabhan, Sandosh, Pak, Hui-Nam, Paré, Guillaume, Pedersen, Nancy L., Pera, Joanna, Pereira, Alexandre, Porteous, David, Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Rader, Daniel J., Refsgaard, Lena, Ribasés, Marta, Ridker, Paul M., Rienstra, Michiel, Risch, Lorenz, Roden, Dan M., Rosand, Jonathan, Rosenberg, Michael A., Rost, Natalia, Rotter, Jerome I., Saba, Samir, Sandhu, Roopinder K., Schnabel, Renate B., Schramm, Katharina, Schunkert, Heribert, Schurman, Claudia, Scott, Stuart A., Seppälä, Ilkka, Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Siland, Joylene E., Sinisalo, Juha, Sinner, Moritz F., Slowik, Agnieszka, Smith, Albert V., Smith, Blair H., Smith, J. Gustav, Smith, Jonathan D., Smith, Nicholas L., Soliman, Elsayed Z., Sotoodehnia, Nona, Stricker, Bruno H., Sun, Albert, Sun, Han, Svendsen, Jesper H., Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Teder-Laving, Maris, Teumer, Alexander, Thériault, Sébastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Gelder, Isabelle C., Van Wagoner, David R., Verweij, Niek, Vlachopoulou, Efthymia, Völker, Uwe, Wang, Biqi, Weeke, Peter E., Weijs, Bob, Weiss, Raul, Weiss, Stefan, Wells, Quinn S., Wiggins, Kerri L., Wong, Jorge A., Woo, Daniel, Worrall, Bradford B., Yang, Pil-Sung, Yao, Jie, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A., Lunetta, Kathryn L., and Ellinor, Patrick T.

Published
2018
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24. Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway: a meta-analysis

Author

McKeown, Nicola M., Dashti, Hassan S., Ma, Jiantao, Haslam, Danielle E., Kiefte-de Jong, Jessica C., Smith, Caren E., Tanaka, Toshiko, Graff, Mariaelisa, Lemaitre, Rozenn N., Rybin, Denis, Sonestedt, Emily, Frazier-Wood, Alexis C., Mook-Kanamori, Dennis O., Li, Yanping, Wang, Carol A., Leermakers, Elisabeth T. M., Mikkilä, Vera, Young, Kristin L., Mukamal, Kenneth J., Cupples, L. Adrienne, Schulz, Christina-Alexandra, Chen, Tzu-An, Li-Gao, Ruifang, Huang, Tao, Oddy, Wendy H., Raitakari, Olli, Rice, Kenneth, Meigs, James B., Ericson, Ulrika, Steffen, Lyn M., Rosendaal, Frits R., Hofman, Albert, Kähönen, Mika, Psaty, Bruce M., Brunkwall, Louise, Uitterlinden, Andre G., Viikari, Jorma, Siscovick, David S., Seppälä, Ilkka, North, Kari E., Mozaffarian, Dariush, Dupuis, Josée, Orho-Melander, Marju, Rich, Stephen S., de Mutsert, Renée, Qi, Lu, Pennell, Craig E., Franco, Oscar H., Lehtimäki, Terho, and Herman, Mark A.

Published
2018
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25. OTTERS: a powerful TWAS framework leveraging summary-level reference data

Author

Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., Yang, Jingjing, Dai, Qile, Zhou, Geyu, Zhao, Hongyu, Võsa, Urmo, Franke, Lude, Battle, Alexis, Teumer, Alexander, Lehtimäki, Terho, Raitakari, Olli T., Esko, Tõnu, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Favé, Marie-Julie, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda, Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Epstein, Michael P., and Yang, Jingjing

Abstract

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies., Godkänd;2023;Nivå 0;2023-04-06 (hanlid);Funder: for more funders see the article https://doi.org/10.1038/s41467-023-36862-w

Published
2023
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27. Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes

Author

Mononen, Nina, Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Mishra, Pashupati P., Juonala, Markus, Waldenberger, Melanie, Klopp, Norman, Illig, Thomas, Leiviskä, Jaana, Loo, Britt-Marie, Laaksonen, Reijo, Oksala, Niku, Kähönen, Mika, Hutri-Kähönen, Nina, Raitakari, Olli, Lehtimäki, Terho, and Raitoharju, Emma

Published
2019
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28. Activated immune–inflammatory pathways are associated with long-standing depressive symptoms: Evidence from gene-set enrichment analyses in the Young Finns Study

Author

Elovainio, Marko, Taipale, Tuukka, Seppälä, Ilkka, Mononen, Nina, Raitoharju, Emma, Jokela, Markus, Pulkki-Råback, Laura, Illig, Thomas, Waldenberger, Melanie, Hakulinen, Christian, Hintsa, Taina, Kivimäki, Mika, Kähönen, Mika, Keltikangas-Järvinen, Liisa, Raitakari, Olli, and Lehtimäki, Terho

Published
2015
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30. Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis

Author

Nikkola, Anssi, primary, Mäkelä, Kari, additional, Herzig, Karl-Heinz, additional, Mutt, Shivaprakash, additional, Prasannan, Aishwarya, additional, Seppänen, Hanna, additional, Lehtimäki, Terho, additional, Kähönen, Mika, additional, Raitakari, Olli, additional, Seppälä, Ilkka, additional, Pakkanen, Pihla, additional, Nordback, Isto, additional, Sand, Juhani, additional, and Laukkarinen, Johanna, additional

Published
2022
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33. A genome-wide association study of total child psychiatric problems scores

Author

Neumann, Alexander, primary, Nolte, Ilja M., additional, Pappa, Irene, additional, Ahluwalia, Tarunveer S., additional, Pettersson, Erik, additional, Rodriguez, Alina, additional, Whitehouse, Andrew, additional, van Beijsterveldt, Catharina E. M., additional, Benyamin, Beben, additional, Hammerschlag, Anke R., additional, Helmer, Quinta, additional, Karhunen, Ville, additional, Krapohl, Eva, additional, Lu, Yi, additional, van der Most, Peter J., additional, Palviainen, Teemu, additional, St Pourcain, Beate, additional, Seppälä, Ilkka, additional, Suarez, Anna, additional, Vilor-Tejedor, Natalia, additional, Tiesler, Carla M. T., additional, Wang, Carol, additional, Wills, Amanda, additional, Zhou, Ang, additional, Alemany, Silvia, additional, Bisgaard, Hans, additional, Bønnelykke, Klaus, additional, Davies, Gareth E., additional, Hakulinen, Christian, additional, Henders, Anjali K., additional, Hyppönen, Elina, additional, Stokholm, Jakob, additional, Bartels, Meike, additional, Hottenga, Jouke-Jan, additional, Heinrich, Joachim, additional, Hewitt, John, additional, Keltikangas-Järvinen, Liisa, additional, Korhonen, Tellervo, additional, Kaprio, Jaakko, additional, Lahti, Jari, additional, Lahti-Pulkkinen, Marius, additional, Lehtimäki, Terho, additional, Middeldorp, Christel M., additional, Najman, Jackob M., additional, Pennell, Craig, additional, Power, Chris, additional, Oldehinkel, Albertine J., additional, Plomin, Robert, additional, Räikkönen, Katri, additional, Raitakari, Olli T., additional, Rimfeld, Kaili, additional, Sass, Lærke, additional, Snieder, Harold, additional, Standl, Marie, additional, Sunyer, Jordi, additional, Williams, Gail M., additional, Bakermans-Kranenburg, Marian J., additional, Boomsma, Dorret I., additional, van IJzendoorn, Marinus H., additional, Hartman, Catharina A., additional, and Tiemeier, Henning, additional

Published
2022
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35. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Author

Mills, Melinda C., Tropf, Felix C., Brazel, David M., van Zuydam, Natalie, Vaez, Ahmad, Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexis, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johannes, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Markus, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthias, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Markus, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashis, Scholz, Markus, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Joris, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Johannesson, Magnus, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chris, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Snieder, Harold, Perry, John R. B., Ong, Ken K., den Hoed, Marcel, Barban, Nicola, Day, Felix R., Mills, M. C., Tropf, F. C., Brazel, D. M., van Zuydam, N., Vaez, A., Agbessi, M., Ahsan, H., Alves, I., Andiappan, A. K., Arindrarto, W., Awadalla, P., Battle, A., Beutner, F., Jan Bonder, M., Boomsma, D. I., Christiansen, M. W., Claringbould, A., Deelen, P., Esko, T., Fave, M. -J., Franke, L., Frayling, T., Gharib, S. A., Gibson, G., Heijmans, B. T., Hemani, G., Jansen, R., Kahonen, M., Kalnapenkis, A., Kasela, S., Kettunen, J., Kim, Y., Kirsten, H., Kovacs, P., Krohn, K., Kronberg, J., Kukushkina, V., Kutalik, Z., Lee, B., Lehtimaki, T., Loeffler, M., Marigorta, U. M., Mei, H., Milani, L., Montgomery, G. W., Muller-Nurasyid, M., Nauck, M., Nivard, M. G., Penninx, B. W. J. H., Perola, M., Pervjakova, N., Pierce, B. L., Powell, J., Prokisch, H., Psaty, B. M., Raitakari, O. T., Ripatti, S., Rotzschke, O., Rueger, S., Saha, A., Scholz, M., Schramm, K., Seppala, I., Slagboom, E. P., Stehouwer, C. D. A., Stumvoll, M., Sullivan, P., 't Hoen, P. A. C., Teumer, A., Thiery, J., Tong, L., Tonjes, A., van Dongen, J., van Iterson, M., van Meurs, J., Veldink, J. H., Verlouw, J., Visscher, P. M., Volker, U., Vosa, U., Westra, H. -J., Wijmenga, C., Yaghootkar, H., Yang, J., Zeng, B., Zhang, F., van Greevenbroek, M. M. J., Schalkwijk, C. G., Deelen, J., van Heemst, D., van Duijn, C. M., Hofman, B. A., Isaacs, A., Uitterlinden, A. G., Verbiest, M., Suchiman, H. E. D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Bot, J., Zhernakova, D. V., Luijk, R., Bonder, M. J., Swertz, M. A., van Zwet, E. W., Akimova, E. T., Bergmann, S., Boardman, J. D., Buring, J. E., Cesarini, D., Chasman, D. I., Chavarro, J. E., Cocca, M., Concas, M. P., Davey-Smith, G., Davies, G., Deary, I. J., Gaskins, A. J., de Geus, E. J. C., Gieger, C., Girotto, G., Grabe, H. J., Gunderson, E. P., Harris, K. M., Hartwig, F. P., He, C., Homuth, G., Horta, B. L., Jan Hottenga, J., Huang, H., Hyppӧnen, E., Ikram, M. A., Johannesson, M., Kamali, Z., Kavousi, M., Kraft, P., Kuhnel, B., Langenberg, C., Study, L. C., Lind, P. A., Luan, J., Magi, R., Magnusson, P. K. E., Mahajan, A., Martin, N. G., Mbarek, H., Mccarthy, M. I., Mcmahon, G., Mcqueen, M. B., Medland, S. E., Meitinger, T., Metspalu, A., Mihailov, E., Missmer, S. A., Mollegaard, S., Mook-Kanamori, D. O., Morgan, A., van der Most, P. J., de Mutsert, R., Noordam, R., Power, C., Redmond, P., Rich-Edwards, J. W., Ridker, P. M., Rietveld, C. A., Ring, S. M., Rose, L. M., Rueedi, R., Stefansson, K., Stockl, D., Strauch, K., Thurik, A. R., Timpson, N. J., Turman, C., Wareham, N. J., Willemsen, G., Zhao, J. H., Pers, T. H., Snieder, H., Perry, J. R. B., Ong, K. K., den Hoed, M., Barban, N., Day, F. R., Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Hyppӧnen, Elina, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Consortium, eQTLGen, Consortium, BIOS, Consortium, Human Reproductive Behaviour, Mahajan, A, McCarthy, MI, Mills, Melinda C., Tropf, Felix C., Brazel, David M., Agbessi, Mawussé, Ahsan, Habibul, Alves, Isabel, Andiappan, Anand Kumar, Arindrarto, Wibowo, Awadalla, Philip, Battle, Alexi, Beutner, Frank, Jan Bonder, Marc, Boomsma, Dorret I., Christiansen, Mark W., Claringbould, Annique, Deelen, Patrick, Esko, Tõnu, Favé, Marie-Julie, Franke, Lude, Frayling, Timothy, Gharib, Sina A., Gibson, Greg, Heijmans, Bastiaan T., Hemani, Gibran, Jansen, Rick, Kähönen, Mika, Kalnapenkis, Anette, Kasela, Silva, Kettunen, Johanne, Kim, Yungil, Kirsten, Holger, Kovacs, Peter, Krohn, Knut, Kronberg, Jaanika, Kukushkina, Viktorija, Kutalik, Zoltan, Lee, Bernett, Lehtimäki, Terho, Loeffler, Marku, Marigorta, Urko M., Mei, Hailang, Milani, Lili, Montgomery, Grant W., Müller-Nurasyid, Martina, Nauck, Matthia, Nivard, Michel G., Penninx, Brenda W. J. H., Perola, Marku, Pervjakova, Natalia, Pierce, Brandon L., Powell, Joseph, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ripatti, Samuli, Rotzschke, Olaf, Rüeger, Sina, Saha, Ashi, Scholz, Marku, Schramm, Katharina, Seppälä, Ilkka, Slagboom, Eline P., Stehouwer, Coen D. A., Stumvoll, Michael, Sullivan, Patrick, ‘t Hoen, Peter A. C., Teumer, Alexander, Thiery, Joachim, Tong, Lin, Tönjes, Anke, van Dongen, Jenny, van Iterson, Maarten, van Meurs, Joyce, Veldink, Jan H., Verlouw, Joost, Visscher, Peter M., Völker, Uwe, Võsa, Urmo, Westra, Harm-Jan, Wijmenga, Cisca, Yaghootkar, Hanieh, Yang, Jian, Zeng, Biao, Zhang, Futao, Isaacs, Aaron, Pool, René, Jan Hottenga, Jouke, van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Schalkwijk, Casper G., Zhernakova, Sasha, Tigchelaar, Ettje F., Beekman, Marian, Deelen, Jori, van Heemst, Diana, van den Berg, Leonard H., van Duijn, Cornelia M., Hofman, Bert A., Uitterlinden, André G., Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka D., Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha V., van ’t Hof, Peter, Nooren, Irene, Moed, Matthij, Vermaat, Martijn, Luijk, René, van Dijk, Freerk, Kielbasa, Szymon M., Swertz, Morris A., van Zwet, Erik. W., Akimova, Evelina T., Bergmann, Sven, Boardman, Jason D., Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey-Smith, George, Davies, Gail, Deary, Ian J., Franco, Oscar, Gaskins, Audrey J., de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Grabe, Hans Jörgen, Gunderson, Erica P., Harris, Kathleen Mullan, Hartwig, Fernando P., He, Chunyan, Hill, W. David, Homuth, Georg, Horta, Bernando Lessa, Huang, Hongyang, Ikram, M. Arfan, Johannesson, Magnu, Kamali, Zoha, Kavousi, Maryam, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, McQueen, Matthew B., Medland, Sarah E., Meitinger, Thoma, Metspalu, Andre, Mihailov, Evelin, Missmer, Stacey A., Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nolte, Ilja M., Noordam, Raymond, Peters, Annette, Power, Chri, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Stefánsson, Kári, Stöckl, Dori, Strauch, Konstantin, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Waldenberger, Melanie, Wareham, Nicholas J., Willemsen, Gonneke, Zhao, Jing Hau, Pers, Tune H., Perry, John R. B., Ong, Ken K., Day, Felix R., Sociology [until 2010], Biological Psychology, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Management and Organisation, Urology, Medical Informatics, Department of Marketing Management, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Neurology, Applied Economics, and Life Course Epidemiology (LCE)

Subjects
Male, demography, genetic variants, reproductive biology, externalising behavior, environmental effects, Disease, Genome-wide association studies, Behavioral Neuroscience, 0302 clinical medicine, genetics, media_common, fertility, 0303 health sciences, Reproduction, Incidence (epidemiology), Coitus, Age Factors, Longevity, sexual intercourse, health, Spermatid differentiation, Single Nucleotide, Reproduction/genetics, 3. Good health, Behavioural genetics, Parturition/genetics, Female, infertility, Infertility, genetic variant, Adolescent, Social Psychology, media_common.quotation_subject, Experimental and Cognitive Psychology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Reproductive biology, medicine, Humans, Polymorphism, behavioural genetics, first sexual intercourse, Genetic Association Studies, Demography, 030304 developmental biology, Parturition, Coitus/physiology, medicine.disease, externalising behaviour, Sexual intercourse, Fertility, age, 030217 neurology & neurosurgery, first birth
Abstract

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4–14%] for women born in 1940 to 22% [CI = 19–25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Published
2021
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36. A genome-wide association study of total child psychiatric problems scores

Author

Neumann, Alexander, Nolte, Ilja M, Pappa, Irene, Ahluwalia, Tarunveer S., Pettersson, Erik, Rodriguez, Alina, Whitehouse, Andrew, van Beijsterveldt, Catharina E. M., Benyamin, Beben, Hammerschlag, Anke R., Helmer, Quinta, Karhunen, Ville, Krapohl, Eva, Lu, Yi, van der Most, Peter J., Palviainen, Teemu, Pourcain, Beate St, Seppälä, Ilkka, Suarez, Anna, Vilor-Tejedor, Natalia, Tiesler, Carla M. T., Wang, Carol, Wills, Amanda, Zhou, Ang, Alemany, Silvia, Bisgaard, Hans, Bønnelykke, Klaus, Davies, Gareth E., Hakulinen, Christian, Henders, Anjali K., Hyppönen, Elina, Stokholm, Jakob, Bartels, Meike, Hottenga, Jouke-Jan, Heinrich, Joachim, Hewitt, John, Keltikangas-Järvinen, Liisa, Korhonen, Tellervo, Kaprio, Jaakko, Lahti, Jari, Lahti-Pulkkinen, Marius, Lehtimäki, Terho, Middeldorp, Christel M., Najman, Jackob M., Pennell, Craig, Power, Chris, Oldehinkel, Albertine J., Plomin, Robert, Räikkönen, Katri, Raitakari, Olli T., Rimfeld, Kaili, Sass, Lærke, Snieder, Harold, Standl, Marie, Sunyer, Jordi, Williams, Gail M., Bakermans-Kranenburg, Marian J., Boomsma, Dorret I., van IJzendoorn, Marinus H., Hartman, Catharina A., Tiemeier, Henning, Neumann, Alexander, Nolte, Ilja M, Pappa, Irene, Ahluwalia, Tarunveer S., Pettersson, Erik, Rodriguez, Alina, Whitehouse, Andrew, van Beijsterveldt, Catharina E. M., Benyamin, Beben, Hammerschlag, Anke R., Helmer, Quinta, Karhunen, Ville, Krapohl, Eva, Lu, Yi, van der Most, Peter J., Palviainen, Teemu, Pourcain, Beate St, Seppälä, Ilkka, Suarez, Anna, Vilor-Tejedor, Natalia, Tiesler, Carla M. T., Wang, Carol, Wills, Amanda, Zhou, Ang, Alemany, Silvia, Bisgaard, Hans, Bønnelykke, Klaus, Davies, Gareth E., Hakulinen, Christian, Henders, Anjali K., Hyppönen, Elina, Stokholm, Jakob, Bartels, Meike, Hottenga, Jouke-Jan, Heinrich, Joachim, Hewitt, John, Keltikangas-Järvinen, Liisa, Korhonen, Tellervo, Kaprio, Jaakko, Lahti, Jari, Lahti-Pulkkinen, Marius, Lehtimäki, Terho, Middeldorp, Christel M., Najman, Jackob M., Pennell, Craig, Power, Chris, Oldehinkel, Albertine J., Plomin, Robert, Räikkönen, Katri, Raitakari, Olli T., Rimfeld, Kaili, Sass, Lærke, Snieder, Harold, Standl, Marie, Sunyer, Jordi, Williams, Gail M., Bakermans-Kranenburg, Marian J., Boomsma, Dorret I., van IJzendoorn, Marinus H., Hartman, Catharina A., and Tiemeier, Henning

Abstract

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

Published
2022

38. A genome-wide expression quantitative trait loci analysis of proprotein convertase subtilisin/kexin enzymes identifies a novel regulatory gene variant for FURIN expression and blood pressure

Author

Turpeinen, Hannu, Seppälä, Ilkka, Lyytikäinen, Leo-Pekka, Raitoharju, Emma, Hutri-Kähönen, Nina, Levula, Mari, Oksala, Niku, Waldenberger, Melanie, Klopp, Norman, Illig, Thomas, Mononen, Nina, Laaksonen, Reijo, Raitakari, Olli, Kähönen, Mika, Lehtimäki, Terho, and Pesu, Marko

Published
2015
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40. Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory

Author

van den Berg, Stéphanie M., de Moor, Marleen H. M., McGue, Matt, Pettersson, Erik, Terracciano, Antonio, Verweij, Karin J. H., Amin, Najaf, Derringer, Jaime, Esko, Tõnu, van Grootheest, Gerard, Hansell, Narelle K., Huffman, Jennifer, Konte, Bettina, Lahti, Jari, Luciano, Michelle, Matteson, Lindsay K., Viktorin, Alexander, Wouda, Jasper, Agrawal, Arpana, Allik, Jüri, Bierut, Laura, Broms, Ulla, Campbell, Harry, Smith, George Davey, Eriksson, Johan G., Ferrucci, Luigi, Franke, Barbera, Fox, Jean-Paul, de Geus, Eco J. C., Giegling, Ina, Gow, Alan J., Grucza, Richard, Hartmann, Annette M., Heath, Andrew C., Heikkilä, Kauko, Iacono, William G., Janzing, Joost, Jokela, Markus, Kiemeney, Lambertus, Lehtimäki, Terho, Madden, Pamela A. F., Magnusson, Patrik K. E., Northstone, Kate, Nutile, Teresa, Ouwens, Klaasjan G., Palotie, Aarno, Pattie, Alison, Pesonen, Anu-Katriina, Polasek, Ozren, Pulkkinen, Lea, Pulkki-Råback, Laura, Raitakari, Olli T., Realo, Anu, Rose, Richard J., Ruggiero, Daniela, Seppälä, Ilkka, Slutske, Wendy S., Smyth, David C., Sorice, Rossella, Starr, John M., Sutin, Angelina R., Tanaka, Toshiko, Verhagen, Josine, Vermeulen, Sita, Vuoksimaa, Eero, Widen, Elisabeth, Willemsen, Gonneke, Wright, Margaret J., Zgaga, Lina, Rujescu, Dan, Metspalu, Andres, Wilson, James F., Ciullo, Marina, Hayward, Caroline, Rudan, Igor, Deary, Ian J., Räikkönen, Katri, Arias Vasquez, Alejandro, Costa, Paul T., Keltikangas-Järvinen, Liisa, van Duijn, Cornelia M., Penninx, Brenda W. J. H., Krueger, Robert F., Evans, David M., Kaprio, Jaakko, Pedersen, Nancy L., Martin, Nicholas G., and Boomsma, Dorret I.

Published
2014
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42. Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease

Author

Pitkänen, Niina, primary, Finkenstedt, Armin, additional, Lamina, Claudia, additional, Juonala, Markus, additional, Kähönen, Mika, additional, Mäkelä, Kari-Matti, additional, Dieplinger, Benjamin, additional, Viveiros, Andre, additional, Melmer, Andreas, additional, Leitner, Isabella, additional, Kedenko, Ludmilla, additional, Seppälä, Ilkka, additional, Viikari, Jorma S.A., additional, Mueller, Thomas, additional, Kronenberg, Florian, additional, Paulweber, Bernhard, additional, Lehtimäki, Terho, additional, Zoller, Heinz, additional, Raitakari, Olli T., additional, and Dieplinger, Hans, additional

Published
2021
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43. Mitochondrial genome-wide analysis of nuclear DNA methylation quantitative trait loci

Author

Laaksonen, Jaakko, primary, Mishra, Pashupati P, additional, Seppälä, Ilkka, additional, Raitoharju, Emma, additional, Marttila, Saara, additional, Mononen, Nina, additional, Lyytikäinen, Leo-Pekka, additional, Kleber, Marcus E, additional, Delgado, Graciela E, additional, Lepistö, Maija, additional, Almusa, Henrikki, additional, Ellonen, Pekka, additional, Lorkowski, Stefan, additional, März, Winfried, additional, Hutri-Kähönen, Nina, additional, Raitakari, Olli, additional, Kähönen, Mika, additional, Salonen, Jukka T, additional, and Lehtimäki, Terho, additional

Published
2021
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44. Predicting sudden cardiac death using common genetic risk variants for coronary artery disease

Author

Hernesniemi, Jussi A., Lyytikäinen, Leo-Pekka, Oksala, Niku, Seppälä, Ilkka, Kleber, Marcus E., Mononen, Nina, März, Winfried, Mikkelsson, Jussi, Pessi, Tanja, Louhelainen, Anne-Mari, Martiskainen, Mika, Nikus, Kjell, Klopp, Norman, Waldenberger, Melanie, Illig, Thomas, Kähönen, Mika, Laaksonen, Reijo, Karhunen, Pekka J., and Lehtimäki, Terho

Published
2015
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45. Habitual sleep duration is associated with BMI and macronutrient intake and may be modified by CLOCK genetic variants1-5

Author

Dashti, Hassan S, Follis, Jack L, Smith, Caren E, Tanaka, Toshiko, Cade, Brian E, Gottlieb, Daniel J, Hruby, Adela, Jacques, Paul F, Lamon-Fava, Stefania, Richardson, Kris, Saxena, Richa, Scheer, Frank AJL, Kovanen, Leena, Bartz, Traci M, Perälä, Mia-Maria, Jonsson, Anna, Frazier-Wood, Alexis C, Kalafati, Ioanna-Panagiota, Mikkilä, Vera, Partonen, Timo, Lemaitre, Rozenn N, Lahti, Jari, Hernandez, Dena G, Toft, Ulla, Johnson, Craig W, Kanoni, Stavroula, Raitakari, Olli T, Perola, Markus, Psaty, Bruce M, Ferrucci, Luigi, Grarup, Niels, Highland, Heather M, Rallidis, Loukianos, Kähönen, Mika, Havulinna, Aki S, Siscovick, David S, Räikkönen, Katri, Jørgensen, Torben, Rotter, Jerome I, Deloukas, Panos, Viikari, Jorma SA, Mozaffarian, Dariush, Linneberg, Allan, Seppälä, Ilkka, Hansen, Torben, Salomaa, Veikko, Gharib, Sina A, Eriksson, Johan G, Bandinelli, Stefania, Pedersen, Oluf, Rich, Stephen S, Dedoussis, George, Lehtimäki, Terho, and Ordovás, José M

Published
2015
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48. Continuity of Genetic Risk for Aggressive Behavior Across the Life-Course

Author

van der Laan, Camiel M., Morosoli-García, José J., van de Weijer, Steve G.A., Colodro-Conde, Lucía, Ip, Hill F., Krapohl, Eva M.L., Brikell, Isabell, Sánchez-Mora, Cristina, Nolte, Ilja M., Pourcain, Beate St, Bolhuis, Koen, Palviainen, Teemu, Zafarmand, Hadi, Gordon, Scott, Zayats, Tetyana, Aliev, Fazil, Jiang, Chang, Wang, Carol A., Saunders, Gretchen, Karhunen, Ville, Hammerschlag, Anke R., Adkins, Daniel E., Border, Richard, Peterson, Roseann E., Prinz, Joseph A., Thiering, Elisabeth, Seppälä, Ilkka, Vilor-Tejedor, Natàlia, Ahluwalia, Tarunveer S., Day, Felix R., Allegrini, Andrea G., Rimfeld, Kaili, Chen, Qi, Lu, Yi, Martin, Joanna, Artigas, María Soler, Rovira, Paula, Bosch, Rosa, Español, Gemma, Neumann, Alexander, Middeldorp, Christel, Verhulst, Frank C., Amin, Najaf, Uitterlinden, André G., Perry, John R.B., Heinrich, Joachim, Tiemeier, Henning, Bartels, Meike, Hottenga, Jouke Jan, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Internal Medicine, Ophthalmology, Epidemiology, Public Health, Adult Psychiatry, Epidemiology and Data Science, APH - Aging & Later Life, APH - Methodology, AR&D - Amsterdam Reproduction & Development, Graduate School, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Compulsivity, Impulsivity & Attention, Public and occupational health, APH - Health Behaviors & Chronic Diseases, ACS - Pulmonary hypertension & thrombosis, Biological Psychology, Criminology, APH - Mental Health, APH - Personalized Medicine, Life Course Epidemiology (LCE), Macromolecular Chemistry & New Polymeric Materials, and Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)

Subjects
Adult, medicine.medical_specialty, Multifactorial Inheritance, Adolescent, 0608 Zoology, Development, Young Adult, Life-course, Risk Factors, Polygenic score, Genetics, medicine, ACTION Consortium, Humans, Genetic risk, Child, Genetics (clinical), Ecology, Evolution, Behavior and Systematics, Aged, Netherlands, Original Research, Genetics & Heredity, Aggression, Public health, Australia, Aggressive behavior, Middle Aged, Rolling weights, Early life, Health psychology, 1701 Psychology, Life course approach, medicine.symptom, Psychology, 1109 Neurosciences, Demography
Abstract

We test whether genetic influences that explain individual differences in aggression in early life also explain individual differences across the life-course. In two cohorts from The Netherlands (N = 13,471) and Australia (N = 5628), polygenic scores (PGSs) were computed based on a genome-wide meta-analysis of childhood/adolescence aggression. In a novel analytic approach, we ran a mixed effects model for each age (Netherlands: 12–70 years, Australia: 16–73 years), with observations at the focus age weighted as 1, and decaying weights for ages further away. We call this approach a ‘rolling weights’ model. In The Netherlands, the estimated effect of the PGS was relatively similar from age 12 to age 41, and decreased from age 41–70. In Australia, there was a peak in the effect of the PGS around age 40 years. These results are a first indication from a molecular genetics perspective that genetic influences on aggressive behavior that are expressed in childhood continue to play a role later in life. Supplementary Information The online version contains supplementary material available at 10.1007/s10519-021-10076-6.

Published
2021
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49. Additional file 4 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Author

Gomez-Alonso, Monica Del C., Kretschmer, Anja, Wilson, Rory, Pfeiffer, Liliane, Karhunen, Ville, Seppälä, Ilkka, Weihua Zhang, Mittelstraß, Kirstin, Wahl, Simone, Matias-Garcia, Pamela R., Prokisch, Holger, Horn, Sacha, Meitinger, Thomas, Serrano-Garcia, Luis R., Sebert, Sylvain, Raitakari, Olli, Loh, Marie, Rathmann, Wolfgang, Müller-Nurasyid, Martina, Herder, Christian, Roden, Michael, Hurme, Mikko, Marjo-Riitta Jarvelin, Ala-Korpela, Mika, Kooner, Jaspal S., Peters, Annette, Lehtimäki, Terho, Chambers, John C., Gieger, Christian, Kettunen, Johannes, and Waldenberger, Melanie

Subjects
fungi, food and beverages
Abstract

Additional file 4: Supplemental Results and Methods. In the Supplemental Results section a detailed comparison of the results obtained across cohorts can be found. In the Supplemental Methods section a detailed description of data processing for each of the population based cohorts can be found, as well as detailed specification on statistical and multi-omics analyses.

Published
2021
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50. Additional file 18 of DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures

Author

Gomez-Alonso, Monica Del C., Kretschmer, Anja, Wilson, Rory, Pfeiffer, Liliane, Karhunen, Ville, Seppälä, Ilkka, Weihua Zhang, Mittelstraß, Kirstin, Wahl, Simone, Matias-Garcia, Pamela R., Prokisch, Holger, Horn, Sacha, Meitinger, Thomas, Serrano-Garcia, Luis R., Sebert, Sylvain, Raitakari, Olli, Loh, Marie, Rathmann, Wolfgang, Müller-Nurasyid, Martina, Herder, Christian, Roden, Michael, Hurme, Mikko, Marjo-Riitta Jarvelin, Ala-Korpela, Mika, Kooner, Jaspal S., Peters, Annette, Lehtimäki, Terho, Chambers, John C., Gieger, Christian, Kettunen, Johannes, and Waldenberger, Melanie

Abstract

Additional file 18: Figure S4. ROC curves for significant CpG-outcome associations: Presented are the receiver operating characteristic (ROC) curves for each outcome-CpG pair for which there exists a statistically significant association for either M1 or M2 (Table 3). The red line is the ROC curve for the model without the CpG, and the green line is the model with the CpG. Presented are also the areas under the curve (AUC) for the respective ROCs, and a p value for the null hypothesis that the addition of the CpG to the model has no effect on the predictive performance of the model. The p value was determined using the R package pROC [87], command roc.test, method “bootstrap”. The analysis was run in the KORA F4 dataset, and, to ensure comparability of the results, the ROC curves were generated using individuals with no missing values in any of the outcomes or covariates, and the methylation data were mean imputed.

Published
2021
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