2,825 results on '"Kaprio J"'
Search Results
2. Sleep inertia, not chronotype, is a marker of circadian misalignment and a risk factor for psychiatric disorders: genetic and epidemiological evidence
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Burns, A., primary, Sinnott-Armstrong, N., additional, Daghlas, I., additional, Windred, D., additional, Phillips, A., additional, Cain, S., additional, Rutter, M., additional, Jones, S., additional, Weedon, M., additional, Wood, A., additional, Kantojärvi, K., additional, Palviainen, T., additional, Udler, M., additional, Dashti, H., additional, Paunio, T., additional, Kaprio, J., additional, Pritchard, J., additional, Ollila, H., additional, Saxena, R., additional, and Lane, J., additional
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- 2024
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3. Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.
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Stringer, S, Minică, CC, Verweij, KJH, Mbarek, H, Bernard, M, Derringer, J, van Eijk, KR, Isen, JD, Loukola, A, Maciejewski, DF, Mihailov, E, van der Most, PJ, Sánchez-Mora, C, Roos, L, Sherva, R, Walters, R, Ware, JJ, Abdellaoui, A, Bigdeli, TB, Branje, SJT, Brown, SA, Bruinenberg, M, Casas, M, Esko, T, Garcia-Martinez, I, Gordon, SD, Harris, JM, Hartman, CA, Henders, AK, Heath, AC, Hickie, IB, Hickman, M, Hopfer, CJ, Hottenga, JJ, Huizink, AC, Irons, DE, Kahn, RS, Korhonen, T, Kranzler, HR, Krauter, K, van Lier, PAC, Lubke, GH, Madden, PAF, Mägi, R, McGue, MK, Medland, SE, Meeus, WHJ, Miller, MB, Montgomery, GW, Nivard, MG, Nolte, IM, Oldehinkel, AJ, Pausova, Z, Qaiser, B, Quaye, L, Ramos-Quiroga, JA, Richarte, V, Rose, RJ, Shin, J, Stallings, MC, Stiby, AI, Wall, TL, Wright, MJ, Koot, HM, Paus, T, Hewitt, JK, Ribasés, M, Kaprio, J, Boks, MP, Snieder, H, Spector, T, Munafò, MR, Metspalu, A, Gelernter, J, Boomsma, DI, Iacono, WG, Martin, NG, Gillespie, NA, Derks, EM, and Vink, JM
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Humans ,Marijuana Abuse ,Carrier Proteins ,Potassium Channels ,Cell Adhesion Molecules ,Membrane Proteins ,Marijuana Smoking ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Genome-Wide Association Study ,Young Adult ,CD56 Antigen ,Potassium Channels ,Sodium-Activated ,and over ,Sodium-Activated ,Antigens ,CD56 ,Genetics ,Tobacco ,Substance Abuse ,Human Genome ,Drug Abuse ,Brain Disorders ,Pediatric Research Initiative ,Tobacco Smoke and Health ,Prevention ,Biotechnology ,Clinical Research ,2.1 Biological and endogenous factors ,Mental Health ,Psychology ,Clinical Sciences ,Public Health and Health Services - Abstract
Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P
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- 2016
4. Ketone body 3-hydroxybutyrate as a biomarker of aggression
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Whipp, A. M., Vuoksimaa, E., Korhonen, T., Pool, R., But, A., Ligthart, L., Hagenbeek, F. A., Bartels, M., Bogl, L. H., Pulkkinen, L., Rose, R. J., Boomsma, D. I., and Kaprio, J.
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- 2021
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5. Accuracy of self-reported anthropometric measures — Findings from the Finnish Twin Study
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Tuomela, J., Kaprio, J., Sipilä, P.N., Silventoinen, K., Wang, X., Ollikainen, M., and Piirtola, M.
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- 2019
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6. A genome-wide association study of anorexia nervosa
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Boraska, V, Franklin, CS, Floyd, JAB, Thornton, LM, Huckins, LM, Southam, L, Rayner, NW, Tachmazidou, I, Klump, KL, Treasure, J, Lewis, CM, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, RAH, Kas, MJH, Favaro, A, Santonastaso, P, Fernández-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori, A, Van Furth, EF, Slof-Op 't Landt, MCT, Hudson, JI, Reichborn-Kjennerud, T, Knudsen, GPS, Monteleone, P, Kaplan, AS, Karwautz, A, Hakonarson, H, Berrettini, WH, Guo, Y, Li, D, Schork, NJ, Komaki, G, Ando, T, Inoko, H, Esko, T, Fischer, K, Männik, K, Metspalu, A, Baker, JH, Cone, RD, Dackor, J, DeSocio, JE, Hilliard, CE, O'Toole, JK, Pantel, J, Szatkiewicz, JP, Taico, C, Zerwas, S, Trace, SE, Davis, OSP, Helder, S, Bühren, K, Burghardt, R, de Zwaan, M, Egberts, K, Ehrlich, S, Herpertz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Scherag, S, Zipfel, S, Boni, C, Ramoz, N, Versini, A, Brandys, MK, Danner, UN, de Kovel, C, Hendriks, J, Koeleman, BPC, Ophoff, RA, Strengman, E, van Elburg, AA, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramís, G, Jiménez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, PE, Tortorella, A, and Maj, M
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Anorexia ,Mental Health ,Serious Mental Illness ,Human Genome ,Eating Disorders ,Clinical Research ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Anorexia Nervosa ,Asian People ,Calcineurin ,Carrier Proteins ,Case-Control Studies ,Cullin Proteins ,Female ,Genome-Wide Association Study ,Guanine Nucleotide Exchange Factors ,Humans ,Japan ,Male ,Meta-Analysis as Topic ,Nuclear Proteins ,Polymorphism ,Single Nucleotide ,White People ,anorexia nervosa ,body mass index ,eating disorders ,genome-wide association study ,GWAS ,metabolic ,Wellcome Trust Case Control Consortium 3 ,Biological Sciences ,Medical and Health Sciences ,Psychology and Cognitive Sciences ,Psychiatry - Abstract
Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.
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- 2014
7. Genome-wide association analysis identifies six new loci associated with forced vital capacity
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Loth, DW, Artigas, MS, Gharib, SA, Wain, LV, Franceschini, N, Koch, B, Pottinger, TD, Smith, AV, Duan, Q, Oldmeadow, C, Lee, MK, Strachan, DP, James, AL, Huffman, JE, Vitart, V, Ramasamy, A, Wareham, NJ, Kaprio, J, Wang, XQ, Trochet, H, Kähönen, M, Flexeder, C, Albrecht, E, Lopez, LM, De Jong, K, Thyagarajan, B, Alves, AC, Enroth, S, Omenaas, E, Joshi, PK, Fall, T, Viñuela, A, Launer, LJ, Loehr, LR, Fornage, M, Li, G, Wilk, JB, Tang, W, Manichaikul, A, Lahousse, L, Harris, TB, North, KE, Rudnicka, AR, Hui, J, Gu, X, Lumley, T, Wright, AF, Hastie, ND, Campbell, S, Kumar, R, Pin, I, Scott, RA, Pietiläinen, KH, Surakka, I, Liu, Y, Holliday, EG, Schulz, H, Heinrich, J, Davies, G, Vonk, JM, Wojczynski, M, Pouta, A, Johansson, A, Wild, SH, Ingelsson, E, Rivadeneira, F, Völzke, H, Hysi, PG, Eiriksdottir, G, Morrison, AC, Rotter, JI, Gao, W, Postma, DS, White, WB, Rich, SS, Hofman, A, Aspelund, T, Couper, D, Smith, LJ, Psaty, BM, Lohman, K, Burchard, EG, Uitterlinden, AG, Garcia, M, Joubert, BR, McArdle, WL, Musk, AB, Hansel, N, Heckbert, SR, Zgaga, L, Van Meurs, JBJ, Navarro, P, Rudan, I, Oh, YM, Redline, S, Jarvis, DL, Zhao, JH, Rantanen, T, O'Connor, GT, and Ripatti, S
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Developmental Biology ,Medical and Health Sciences ,Biological Sciences - Abstract
Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10-8) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.© 2014 Nature America, Inc. All rights reserved.
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- 2014
8. The association of depressive symptoms with perceived occupational noise exposure in young adults
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Heinonen-Guzejev, M, primary, Whipp, A M, additional, Wang, Z, additional, Anu Ranjit, A, additional, Palviainen, T, additional, van Kamp, I, additional, and Kaprio, J, additional
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- 2023
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9. Phospholipids and insulin resistance in psychosis: A lipidomics study of twin pairs discordant for schizophrenia
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Orešič, M, Seppänen-Laakso, T, Sun, D, Tang, J, Therman, S, Viehman, R, Mustonen, U, van Erp, TG, Hyötyläinen, T, Thompson, P, Toga, AW, Huttunen, MO, Suvisaari, J, Kaprio, J, Lönnqvist, J, and Cannon, TD
- Abstract
Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.Methods: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins. © 2012 Orešič et al.; licensee BioMed Central Ltd.
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- 2012
10. Plasma cell-free DNA methylation marks for episodic memory impairment: a pilot twin study
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Konki, M., Lindgren, N., Kyläniemi, M., Venho, R., Laajala, E., Ghimire, B., Lahesmaa, R., Kaprio, J., Rinne, J. O., and Lund, R. J.
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- 2020
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11. Genetic influences on human brain morphology
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Van Erp, TGM, Cannon, TD, Tran, HL, Wobbekind, AD, Huttunen, M, Lönnqvist, J, Kaprio, J, Salonen, O, Valanne, L, Poutanen, VP, Standertskjöld-Nordenstam, CG, Toga, AW, and Thompson, PM
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heritability ,brain ,cortex ,twin - Abstract
Structural magnetic resonance imaging (MRI) studies have started to address the contributions of genetic and environmental factors to brain morphology in healthy individuals. These studies have largely been limited to assessing heritability for single and mostly gross anatomical structures. To avoid this limitation, we developed a method using high-dimensional 3D nonlinear registration to apply an elastic deformation vector field in the cortical parameter space and assess regional cortical gray matter density on the entire cortical surface in healthy monozygotic (MZ) and dizygotic (DZ) twins. Once aligned across subjects, surface maps of gray matter density were subjected to variance component analyses. By fitting structural equation models, we generated cortical surface maps to reflect the regional percent variance explained by genetic, shared and unique environmental factors. Initial analyses suggest that cortical structure in primary motor and sensory areas is highly heritable with variance components for additive genetic influences reaching as high as 70%. ©2004 IEEE.
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- 2004
12. Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence
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Hancock, D B, Guo, Y, Reginsson, G W, Gaddis, N C, Lutz, S M, Sherva, R, Loukola, A, Minica, C C, Markunas, C A, Han, Y, Young, K A, Gudbjartsson, D F, Gu, F, McNeil, D W, Qaiser, B, Glasheen, C, Olson, S, Landi, M T, Madden, P A F, Farrer, L A, Vink, J, Saccone, N L, Neale, M C, Kranzler, H R, McKay, J, Hung, R J, Amos, C I, Marazita, M L, Boomsma, D I, Baker, T B, Gelernter, J, Kaprio, J, Caporaso, N E, Thorgeirsson, T E, Hokanson, J E, Bierut, L J, Stefansson, K, and Johnson, E O
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- 2018
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13. Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study
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Lapatto, H. A. (Helena A. K.), Kuusela, M. (Minna), Heikkinen, A. (Aino), Muniandy, M. (Maheswary), van der Kolk, B. W. (Birgitta W.), Gopalakrishnan, S. (Swetha), Pöllänen, N. (Noora), Sandvik, M. (Martin), Schmidt, M. S. (Mark S.), Heinonen, S. (Sini), Saari, S. (Sina), Kuula, J. (Juho), Hakkarainen, A. (Antti), Tampio, J. (Janne), Saarinen, T. (Tuure), Taskinen, M.-R. (Marja-Riitta), Lundbom, N. (Nina), Groop, P.-H. (Per-Henrik), Tiirola, M. (Marja), Katajisto, P. (Pekka), Lehtonen, M. (Marko), Brenner, C. (Charles), Kaprio, J. (Jaakko), Pekkala, S. (Satu), Ollikainen, M. (Miina), Pietiläinen, K. H. (Kirsi H.), Pirinen, E. (Eija), Lapatto, H. A. (Helena A. K.), Kuusela, M. (Minna), Heikkinen, A. (Aino), Muniandy, M. (Maheswary), van der Kolk, B. W. (Birgitta W.), Gopalakrishnan, S. (Swetha), Pöllänen, N. (Noora), Sandvik, M. (Martin), Schmidt, M. S. (Mark S.), Heinonen, S. (Sini), Saari, S. (Sina), Kuula, J. (Juho), Hakkarainen, A. (Antti), Tampio, J. (Janne), Saarinen, T. (Tuure), Taskinen, M.-R. (Marja-Riitta), Lundbom, N. (Nina), Groop, P.-H. (Per-Henrik), Tiirola, M. (Marja), Katajisto, P. (Pekka), Lehtonen, M. (Marko), Brenner, C. (Charles), Kaprio, J. (Jaakko), Pekkala, S. (Satu), Ollikainen, M. (Miina), Pietiläinen, K. H. (Kirsi H.), and Pirinen, E. (Eija)
- Abstract
Nicotinamide adenine dinucleotide (NAD⁺) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)–discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD⁺ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD⁺ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.
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- 2023
14. Persistent leisure-time physical activity in adulthood and use of antidepressants: A follow-up study among twins
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Waller, K., Kaprio, J., Korhonen, T., Tuulio-Henriksson, A., and Kujala, U.M.
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- 2016
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15. New insights into the genetic etiology of Alzheimer's disease and related dementias
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Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., Holmans, P. A., Boland, A., Damotte, V., van der Lee, S. J., Costa, M. R., Kuulasmaa, T., Yang, Q., de Rojas, I., Bis, J. C., Yaqub, A., Prokic, I., Chapuis, J., Ahmad, S., Giedraitis, V., Aarsland, D., Garcia-Gonzalez, P., Abdelnour, C., Alarcón-Martín, E., Alcolea, D., Alegret, M., Alvarez, I., Álvarez, V., Armstrong, N. J., Tsolaki, A., Antúnez, C., Appollonio, I., Arcaro, M., Archetti, S., Pastor, A. A., Arosio, B., Athanasiu, L., Bailly, H., Banaj, N., Baquero, M., Barral, S., Beiser, A., Pastor, A. B., Below, J. E., Benchek, P., Benussi, L., Berr, C., Besse, C., Bessi, V., Binetti, G., Bizarro, A., Blesa, R., Boada, M., Boerwinkle, E., Borroni, B., Boschi, S., Bossù, P., Bråthen, G., Bressler, J., Bresner, C., Brodaty, H., Brookes, K. J., Brusco, L. I., Buiza-Rueda, D., Bûrger, K., Burholt, V., Bush, W. S., Calero, M., Cantwell, L. B., Chene, G., Chung, J., Cuccaro, M. L., Carracedo, Á., Cecchetti, R., Cervera-Carles, L., Charbonnier, C., Chen, H. -H., Chillotti, C., Ciccone, S., Claassen, J. A. H. R., Clark, C., Conti, E., Corma-Gómez, A., Costantini, E., Custodero, C., Daian, D., Dalmasso, M. C., Daniele, A., Dardiotis, E., Dartigues, J. -F., de Deyn, P. P., de Paiva Lopes, K., de Witte, L. D., Debette, S., Deckert, J., del Ser, T., Denning, N., Destefano, A., Dichgans, M., Diehl-Schmid, J., Diez-Fairen, M., Rossi, P. D., Djurovic, S., Duron, E., Düzel, E., Dufouil, C., Eiriksdottir, G., Engelborghs, S., Escott-Price, V., Espinosa, A., Ewers, M., Faber, K. M., Fabrizio, T., Nielsen, S. F., Fardo, D. W., Farotti, L., Fenoglio, C., Fernández-Fuertes, M., Ferrari, R., Ferreira, C. B., Ferri, E., Fin, B., Fischer, P., Fladby, T., Fließbach, K., Fongang, B., Fornage, M., Fortea, J., Foroud, T. M., Fostinelli, S., Fox, N. C., Franco-Macías, E., Bullido, M. J., Frank-García, A., Froelich, L., Fulton-Howard, B., Galimberti, D., García-Alberca, J. M., García-González, P., Garcia-Madrona, S., Garcia-Ribas, G., Ghidoni, R., Giegling, I., Giorgio, G., Goate, A. M., Goldhardt, O., Gomez-Fonseca, D., González-Pérez, A., Graff, C., Grande, G., Green, E., Grimmer, T., Grünblatt, E., Grunin, M., Gudnason, V., Guetta-Baranes, T., Haapasalo, A., Hadjigeorgiou, G., Haines, J. L., Hamilton-Nelson, K. L., Hampel, H., Hanon, O., Hardy, J., Hartmann, A. M., Hausner, L., Harwood, J., Heilmann-Heimbach, S., Helisalmi, S., Heneka, M. T., Hernández, I., Herrmann, M. J., Hoffmann, P., Holmes, C., Holstege, H., Vilas, R. H., Hulsman, M., Humphrey, J., Biessels, G. J., Jian, X., Johansson, C., Jun, G. R., Kastumata, Y., Kauwe, J., Kehoe, P. G., Kilander, L., Ståhlbom, A. K., Kivipelto, M., Koivisto, A., Kornhuber, J., Kosmidis, M. H., Kukull, W. A., Kuksa, P. P., Kunkle, B. W., Kuzma, A. B., Lage, C., Laukka, E. J., Launer, L., Lauria, A., Lee, C. -Y., Lehtisalo, J., Lerch, O., Lleó, A., Longstreth, W., Lopez, O., de Munain, A. L., Love, S., Löwemark, M., Luckcuck, L., Lunetta, K. L., Ma, Y., Macías, J., Macleod, C. A., Maier, W., Mangialasche, F., Spallazzi, M., Marquié, M., Marshall, R., Martin, E. R., Montes, A. M., Rodríguez, C. M., Masullo, C., Mayeux, R., Mead, S., Mecocci, P., Medina, M., Meggy, A., Mehrabian, S., Mendoza, S., Menéndez-González, M., Mir, P., Moebus, S., Mol, M., Molina-Porcel, L., Montrreal, L., Morelli, L., Moreno, F., Morgan, K., Mosley, T., Nöthen, M. M., Muchnik, C., Mukherjee, S., Nacmias, B., Ngandu, T., Nicolas, G., Nordestgaard, B. G., Olaso, R., Orellana, A., Orsini, M., Ortega, G., Padovani, A., Paolo, C., Papenberg, G., Parnetti, L., Pasquier, F., Pastor, P., Peloso, G., Pérez-Cordón, A., Pérez-Tur, J., Pericard, P., Peters, O., Pijnenburg, Y. A. L., Pineda, J. A., Piñol-Ripoll, G., Pisanu, C., Polak, T., Popp, J., Posthuma, D., Priller, J., Puerta, R., Quenez, O., Quintela, I., Thomassen, J. Q., Rábano, A., Rainero, I., Rajabli, F., Ramakers, I., Real, L. M., Reinders, M. J. T., Reitz, C., Reyes-Dumeyer, D., Ridge, P., Riedel-Heller, S., Riederer, P., Roberto, N., Rodriguez-Rodriguez, E., Rongve, A., Allende, I. R., Rosende-Roca, M., Royo, J. L., Rubino, E., Rujescu, D., Sáez, M. E., Sakka, P., Saltvedt, I., Sanabria, Á., Sánchez-Arjona, M. B., Sanchez-Garcia, F., Juan, P. S., Sánchez-Valle, R., Sando, S. B., Sarnowski, C., Satizabal, C. L., Scamosci, M., Scarmeas, N., Scarpini, E., Scheltens, P., Scherbaum, N., Scherer, M., Schmid, M., Schneider, A., Schott, J. M., Selbæk, G., Seripa, D., Serrano, M., Sha, J., Shadrin, A. A., Skrobot, O., Slifer, S., Snijders, G. J. L., Soininen, H., Solfrizzi, V., Solomon, A., Song, Y. E., Sorbi, S., Sotolongo-Grau, O., Spalletta, G., Spottke, A., Squassina, A., Stordal, E., Tartan, J. 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[0000-0003-2617-3009], Bossù, Paola [0000-0002-1432-0078], Bråthen, Geir [0000-0003-3224-7983], Bressler, Jan [0000-0001-6578-4772], Bresner, Catherine [0000-0003-2673-9762], Brodaty, Henry [0000-0001-9487-6617], Brookes, Keeley J [0000-0003-2427-2513], Burholt, Vanessa [0000-0002-6789-127X], Bush, William S [0000-0002-9729-6519], Calero, Miguel [0000-0001-5366-3324], Chung, Jaeyoon [0000-0002-6431-9454], Cervera-Carles, Laura [0000-0003-2286-200X], Costantini, Emanuele [0000-0002-1096-8221], Dalmasso, Maria Carolina [0000-0002-4901-9955], de Paiva Lopes, Katia [0000-0002-0240-0126], de Witte, Lot D [0000-0002-7235-9958], Debette, Stéphanie [0000-0001-8675-7968], Del Ser, Teodoro [0000-0001-9806-7083], Dichgans, Martin [0000-0002-0654-387X], Diehl-Schmid, Janine [0000-0002-7745-1382], Diez-Fairen, Mónica [0000-0003-1882-0309], Djurovic, Srdjan [0000-0002-8140-8061], Dufouil, Carole [0000-0003-2442-4476], Escott-Price, Valentina [0000-0003-1784-5483], Ewers, Michael 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[0000-0002-7542-1139], Kornhuber, Johannes [0000-0002-8096-3987], Kosmidis, Mary H [0000-0001-8790-1220], Lage, Carmen [0000-0003-1703-121X], Launer, Lenore [0000-0002-3238-7612], Lee, Chien-Yueh [0000-0002-4304-974X], Lleó, Alberto [0000-0002-2568-5478], Lopez, Oscar [0000-0002-8546-8256], de Munain, Adolfo Lopez [0000-0002-9509-4032], Lunetta, Kathryn L [0000-0002-9268-810X], Ma, Yiyi [0000-0002-3609-8877], MacLeod, Catherine A [0000-0002-9314-7380], Marquié, Marta [0000-0002-0660-0950], Montes, Angel Martín [0000-0002-1694-786X], Mead, Simon [0000-0002-4326-1468], Medina, Miguel [0000-0002-7016-5340], Menéndez-González, Manuel [0000-0002-5218-0774], Mol, Merel [0000-0003-2533-2530], Morgan, Kevin [0000-0002-8217-2396], Nöthen, Markus M [0000-0002-8770-2464], Muchnik, Carolina [0000-0002-1542-3706], Nacmias, Benedetta [0000-0001-9338-9040], Nicolas, Gael [0000-0001-9391-7800], Nordestgaard, Børge G [0000-0002-1954-7220], Pasquier, Florence [0000-0001-9880-9788], Pastor, Pau [0000-0002-7493-8777], Peloso, Gina [0000-0002-5355-8636], Pérez-Cordón, Alba [0000-0002-6028-0791], Pérez-Tur, Jordi [0000-0002-9111-1712], Pericard, Pierre [0000-0001-8167-6448], Pineda, Juan A [0000-0002-3751-0296], Pisanu, Claudia [0000-0002-9151-4319], Posthuma, Danielle [0000-0001-7582-2365], Puerta, Raquel [0000-0002-1191-5893], Quenez, Olivier [0000-0002-8273-8505], Thomassen, Jesper Qvist [0000-0003-3484-9531], Real, Luis M [0000-0003-4932-7429], Reinders, Marcel JT [0000-0002-1148-1562], Reitz, Christiane [0000-0001-8757-7889], Riedel-Heller, Steffi [0000-0003-4321-6090], Rodriguez-Rodriguez, Eloy [0000-0001-7742-677X], Rongve, Arvid [0000-0002-0476-4134], Sáez, María Eugenia [0000-0001-9299-2534], Saltvedt, Ingvild [0000-0002-7897-9808], Juan, Pascual Sánchez [0000-0002-6081-8037], Sarnowski, Chloé [0000-0002-6090-7099], Satizabal, Claudia L [0000-0002-1115-4430], Schott, Jonathan M [0000-0003-2059-024X], Selbæk, Geir [0000-0001-6511-8219], Shadrin, Alexey A [0000-0002-7467-250X], Soininen, Hilkka [0000-0002-2785-9937], Solfrizzi, Vincenzo [0000-0002-8524-0315], Song, Yeunjoo [0000-0002-7452-3731], Sotolongo-Grau, Oscar [0000-0002-9679-0670], Spalletta, Gianfranco [0000-0002-7432-4249], Squassina, Alessio [0000-0001-7415-7607], Stordal, Eystein [0000-0002-2443-7923], Tosto, Giuseppe [0000-0001-7075-8245], Uitterlinden, Andre [0000-0002-7276-3387], Valladares, Otto [0000-0001-8055-2187], Broeckhoven, Christine Van [0000-0003-0183-7665], Vidal, Jean-Sébastien [0000-0001-6770-0720], Vogelgsang, Jonathan [0000-0001-9326-8193], Wagner, Michael [0000-0003-2589-6440], Wallon, David [0000-0002-2634-7198], Wiltfang, Jens [0000-0003-1492-5330], Woods, Bob [0000-0002-6781-651X], Yannakoulia, Mary [0000-0003-2171-7337], Zare, Habil [0000-0001-5902-6238], Zhang, Xiaoling [0000-0001-8237-1857], Farrer, Lindsay A [0000-0001-5533-4225], Psaty, Bruce M [0000-0002-7278-2190], Ghanbari, Mohsen [0000-0002-9476-7143], Raj, Towfique [0000-0002-9355-5704], Sachdev, Perminder [0000-0002-9595-3220], Mather, Karen [0000-0003-4143-8941], Ikram, M Arfan [0000-0003-0372-8585], Tsolaki, Magda [0000-0002-2072-8010], Pericak-Vance, Margaret A [0000-0001-7283-8804], Amouyel, Philippe [0000-0001-9088-234X], Williams, Julie [0000-0002-4069-0259], Frikke-Schmidt, Ruth [0000-0003-4084-5027], Seshadri, Sudha [0000-0001-6135-2622], Andreassen, Ole A [0000-0002-4461-3568], Sleegers, Kristel [0000-0002-0283-2332], van Duijn, Cornelia M [0000-0002-2374-9204], Sims, Rebecca [0000-0002-3885-1199], van der Flier, Wiesje M [0000-0001-8766-6224], Ramirez, Alfredo [0000-0003-4991-763X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Complex Trait Genetics, Clinical sciences, Neuroprotection & Neuromodulation, Pathologic Biochemistry and Physiology, Clinical Biology, Epidemiology, Internal Medicine, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Psychiatrie (9), UAM. Departamento de Biología Molecular, University of Helsinki, Department of Neurosciences, HUS Internal Medicine and Rehabilitation, Timo Strandberg / Principal Investigator, Department of Medicine, Clinicum, HUS Neurocenter, Neurologian yksikkö, Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale (France), European Commission, LabEx DISTALZ, Pérez-Tur, Jordi, University Children’s Hospital Basel (Suiza), INSERM (Francia), Lille Métropole Communauté Urbaine, Government of France (Francia), EADB, GR@ACE, DEGESCO, EADI, GERAD, Demgene, FinnGen, ADGC, CHARGE, Holmans, Peter A. [0000-0003-0870-9412], van der Lee, Sven J. [0000-0003-1606-8643], Costa, Marcos R. [0000-0002-4928-2163], Bis, Joshua C. [0000-0002-3409-1110], Brookes, Keeley J. [0000-0003-2427-2513], Bush, William S. [0000-0002-9729-6519], de Witte, Lot D. [0000-0002-7235-9958], del Ser, Teodoro [0000-0001-9806-7083], Fox, Nick C. [0000-0002-6660-657X], Bullido, María J. [0000-0002-6477-1117], Goate, Alison M. [0000-0002-0576-2472], Herrmann, Martin J. [0000-0001-9970-2122], Jun, Gyungah R. [0000-0002-3230-8697], Kehoe, Patrick G. [0000-0002-7542-1139], Kosmidis, Mary H. [0000-0001-8790-1220], Lunetta, Kathryn L. [0000-0002-9268-810X], MacLeod, Catherine A. [0000-0002-9314-7380], Nöthen, Markus M. [0000-0002-8770-2464], Nordestgaard, Børge G. [0000-0002-1954-7220], Pineda, Juan A. [0000-0002-3751-0296], Real, Luis M. [0000-0003-4932-7429], Reinders, Marcel J. T. [0000-0002-1148-1562], Satizabal, Claudia L. [0000-0002-1115-4430], Schott, Jonathan M. [0000-0003-2059-024X], Shadrin, Alexey A. [0000-0002-7467-250X], Farrer, Lindsay A. [0000-0001-5533-4225], Psaty, Bruce M. [0000-0002-7278-2190], Ikram, M. Arfan [0000-0003-0372-8585], Pericak-Vance, Margaret A. [0000-0001-7283-8804], Andreassen, Ole A. [0000-0002-4461-3568], van Duijn, Cornelia M. [0000-0002-2374-9204], van der Flier, Wiesje M. [0000-0001-8766-6224], and Molecular Neuroscience and Ageing Research (MOLAR)
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tau Proteins/genetics ,Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1] ,Neurologi ,MED/03 - GENETICA MEDICA ,45/43 ,Medizin ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,genetics [Alzheimer Disease] ,Genome-Wide Association Study ,Humans ,tau Proteins ,Alzheimer Disease ,Cognitive Dysfunction ,VARIANTS ,pathology [Alzheimer Disease] ,Tau Proteins ,Settore BIO/13 - Biologia Applicata ,Cognitive Dysfunction/psychology ,692/699/375/365/1283 ,IMPUTATION ,article ,1184 Genetics, developmental biology, physiology ,Biología y Biomedicina / Biología ,AMYLOID-BETA ,Settore MED/26 - NEUROLOGIA ,Neurology ,psychology [Cognitive Dysfunction] ,Medical Genetics ,Human ,Neuroscience(all) ,631/208/205/2138 ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,ddc:570 ,Genetics ,Genetic Predisposition to Disease ,GENOME-WIDE ASSOCIATION ,METAANALYSIS ,Medicinsk genetik ,MED/26 - NEUROLOGIA ,Alzheimer Disease/genetics ,neurology ,tau Protein ,NECROSIS-FACTOR-ALPHA ,RISK LOCI ,genetics [tau Proteins] ,PREDICTION MODELS ,Human medicine ,GENERATION ,RESPONSES - Abstract
25 páginas, 6 figuras, 2 tablas, Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele., This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government’s LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not
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- 2022
16. Physical activity, cardiorespiratory fitness, and metabolic outcomes in monozygotic twin pairs discordant for body mass index
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Berntzen, B., Jukarainen, S., Kataja, M., Hakkarainen, A., Lundbom, J., Lundbom, N., Tammelin, T., Simonen, R., Piirilä, P., Rissanen, A., Kaprio, J., Paavonen, E. J., and Pietiläinen, K. H.
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- 2018
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17. Diversity of leisure‐time sport activities in adolescence as a predictor of leisure‐time physical activity in adulthood
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Mäkelä, S., Aaltonen, S., Korhonen, T., Rose, R. J., and Kaprio, J.
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- 2017
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18. An epigenome-wide association study meta-analysis of educational attainment
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Linnér, R Karlsson, Marioni, R E, Rietveld, C A, Simpkin, A J, Davies, N M, Watanabe, K, Armstrong, N J, Auro, K, Baumbach, C, Bonder, M J, Buchwald, J, Fiorito, G, Ismail, K, Iurato, S, Joensuu, A, Karell, P, Kasela, S, Lahti, J, McRae, A F, Mandaviya, P R, Seppälä, I, Wang, Y, Baglietto, L, Binder, E B, Harris, S E, Hodge, A M, Horvath, S, Hurme, M, Johannesson, M, Latvala, A, Mather, K A, Medland, S E, Metspalu, A, Milani, L, Milne, R L, Pattie, A, Pedersen, N L, Peters, A, Polidoro, S, Räikkönen, K, Severi, G, Starr, J M, Stolk, L, Waldenberger, M, Consortium, B IOS, Eriksson, J G, Esko, T, Franke, L, Gieger, C, Giles, G G, Hägg, S, Jousilahti, P, Kaprio, J, Kähönen, M, Lehtimäki, T, Martin, N G, van Meurs, J BC, Ollikainen, M, Perola, M, Posthuma, D, Raitakari, O T, Sachdev, P S, Taskesen, E, Uitterlinden, A G, Vineis, P, Wijmenga, C, Wright, M J, Relton, C, Smith, G Davey, Deary, I J, Koellinger, P D, and Benjamin, D J
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- 2017
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19. Biotin-dependent functions in adiposity: a study of monozygotic twin pairs
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Järvinen, E, Ismail, K, Muniandy, M, Bogl, L H, Heinonen, S, Tummers, M, Miettinen, S, Kaprio, J, Rissanen, A, Ollikainen, M, and Pietiläinen, K H
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- 2016
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20. DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs
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Pietiläinen, K H, Ismail, K, Järvinen, E, Heinonen, S, Tummers, M, Bollepalli, S, Lyle, R, Muniandy, M, Moilanen, E, Hakkarainen, A, Lundbom, J, Lundbom, N, Rissanen, A, Kaprio, J, and Ollikainen, M
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- 2016
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21. Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects
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Howe, LJ, Nivard, MG, Morris, TT, Hansen, AF, Rasheed, H, Cho, Y, Chittoor, G, Ahlskog, R, Lind, PA, Palviainen, T, van der Zee, MD, Cheesman, R, Mangino, M, Wang, Y, Li, S, Klaric, L, Ratliff, SM, Bielak, LF, Nygaard, M, Giannelis, A, Willoughby, EA, Reynolds, CA, Balbona, JV, Andreassen, OA, Ask, H, Baras, A, Bauer, CR, Boomsma, DI, Campbell, A, Campbell, H, Chen, Z, Christofidou, P, Corfield, E, Dahm, CC, Dokuru, DR, Evans, LM, de Geus, EJC, Giddaluru, S, Gordon, SD, Harden, KP, Hill, WD, Hughes, A, Kerr, SM, Kim, Y, Kweon, H, Latvala, A, Lawlor, DA, Li, L, Lin, K, Magnus, P, Magnusson, PKE, Mallard, TT, Martikainen, P, Mills, MC, Njolstad, PR, Overton, JD, Pedersen, NL, Porteous, DJ, Reid, J, Silventoinen, K, Southey, MC, Stoltenberg, C, Tucker-Drob, EM, Wright, MJ, Hewitt, JK, Keller, MC, Stallings, MC, Lee, JJ, Christensen, K, Kardia, SLR, Peyser, PA, Smith, JA, Wilson, JF, Hopper, JL, Hagg, S, Spector, TD, Pingault, J-B, Plomin, R, Havdahl, A, Bartels, M, Martin, NG, Oskarsson, S, Justice, AE, Millwood, IY, Hveem, K, Naess, O, Willer, CJ, Asvold, BO, Koellinger, PD, Kaprio, J, Medland, SE, Walters, RG, Benjamin, DJ, Turley, P, Evans, DM, Smith, GD, Hayward, C, Brumpton, B, Hemani, G, Davies, NM, Howe, LJ, Nivard, MG, Morris, TT, Hansen, AF, Rasheed, H, Cho, Y, Chittoor, G, Ahlskog, R, Lind, PA, Palviainen, T, van der Zee, MD, Cheesman, R, Mangino, M, Wang, Y, Li, S, Klaric, L, Ratliff, SM, Bielak, LF, Nygaard, M, Giannelis, A, Willoughby, EA, Reynolds, CA, Balbona, JV, Andreassen, OA, Ask, H, Baras, A, Bauer, CR, Boomsma, DI, Campbell, A, Campbell, H, Chen, Z, Christofidou, P, Corfield, E, Dahm, CC, Dokuru, DR, Evans, LM, de Geus, EJC, Giddaluru, S, Gordon, SD, Harden, KP, Hill, WD, Hughes, A, Kerr, SM, Kim, Y, Kweon, H, Latvala, A, Lawlor, DA, Li, L, Lin, K, Magnus, P, Magnusson, PKE, Mallard, TT, Martikainen, P, Mills, MC, Njolstad, PR, Overton, JD, Pedersen, NL, Porteous, DJ, Reid, J, Silventoinen, K, Southey, MC, Stoltenberg, C, Tucker-Drob, EM, Wright, MJ, Hewitt, JK, Keller, MC, Stallings, MC, Lee, JJ, Christensen, K, Kardia, SLR, Peyser, PA, Smith, JA, Wilson, JF, Hopper, JL, Hagg, S, Spector, TD, Pingault, J-B, Plomin, R, Havdahl, A, Bartels, M, Martin, NG, Oskarsson, S, Justice, AE, Millwood, IY, Hveem, K, Naess, O, Willer, CJ, Asvold, BO, Koellinger, PD, Kaprio, J, Medland, SE, Walters, RG, Benjamin, DJ, Turley, P, Evans, DM, Smith, GD, Hayward, C, Brumpton, B, Hemani, G, and Davies, NM
- Abstract
Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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- 2022
22. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis
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Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., Fisher, S.E., Tielbeek, J.J., Uffelmann, E., Williams, B.S., Colodro-Conde, L., Gagnon, É., Mallard, T.T., Levitt, B.E., Jansen, P.R., Johansson, A, Sallis, H.M., Pistis, G., Saunders, G.R.B., Allegrini, A.G., Rimfeld, K., Konte, B., Klein, M., Hartmann, A.M., Salvatore, J.E., Nolte, I.M., Demontis, D., Malmberg, A.L.K., Burt, S.A., Savage, J.E., Sugden, K., Poulton, R., Harris, K.M., Vrieze, S., McGue, M., Iacono, W.G., Roth Mota, N., Mill, J., Viana, J.F., Mitchell, B.L., Morosoli, J.J., Andlauer, T.F.M., Ouellet-Morin, I., Tremblay, R.E., Côté, S.M., Gouin, J.-P., Brendgen, M.R., Dionne, G., Vitaro, F., Lupton, M.K., Martin, N.G., Porjesz, B., Hesselbrock, V., Foroud, T., Agrawal, A., Edenberg, H.J., Liu, Y, Plawecki, M.H., Kuperman, S., Kramer, J.R., Meyers, J.M., Kamarajan, C., Pandey, A., Bierut, L., Rice, J., Bucholz, K.K., Schuckit, M.A., Tischfield, J., Hart, R., Almasy, L., Goate, A., Slesinger, P., Scott, D., Castelao, E., Räikkönen, K., Eriksson, J.G., Lahti, J., Hartman, C.A, Oldehinkel, A.J., Snieder, H., Liu, H., Preisig, M., Whipp, A., Vuoksimaa, E., Lu, Y., Jern, P., Rujescu, D., Giegling, I., Palviainen, T., Kaprio, J., Harden, K.P., Munafò, M.R., Morneau-Vaillancourt, G., Plomin, R., Viding, E., Boutwell, B.B., Aliev, F., Dick, D.M., Popma, A., Faraone, S.V, Børglum, A.D., Medland, S.E., Franke, B., Boivin, M., Pingault, J.-B., Glennon, J.C., Barnes, J.C., and Fisher, S.E.
- Abstract
Item does not contain fulltext
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- 2022
23. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
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Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., Räikkönen, K., Lahti, J., Tuominen, S., Yang, Q., Pergola, G., Ahmad, S., Amin, N., Armstrong, N.J., Beiser, A., Bey, K., Bis, J.C., Boerwinkle, E., Bressler, J., Campbell, A., Campbell, H., Chen, Q., Corley, J., Cox, S.R., Davies, G., De Jager, P.L., Derks, E.M., Faul, J.D., Fitzpatrick, A.L., Fohner, A.E., Ford, I., Fornage, M., Gerring, Z., Grabe, H.J., Grodstein, F., Gudnason, V., Simonsick, E., Holliday, E.G., Joshi, P.K., Kajantie, E., Kaprio, J., Karell, P., Kleineidam, L., Knol, M.J., Kochan, N.A., Kwok, J.B., Leber, M., Lam, M., Lee, T., Li, S., Loukola, A., Luck, T., Marioni, R.E., Mather, K.A., Medland, S., Mirza, S.S., Nalls, M.A., Nho, K., O’Donnell, A., Oldmeadow, C., Painter, J., Pattie, A., Reppermund, S., Risacher, S.L., Rose, R.J., Sadashivaiah, V., Scholz, M., Satizabal, C.L., Schofield, P.W., Schraut, K.E., Scott, R.J., Simino, J., Smith, A.V., Smith, J.A., Stott, D.J., Surakka, I., Teumer, A., Thalamuthu, A., Trompet, S., Turner, S.T., van der Lee, S.J., Villringer, A., Völker, U., Wilson, R.S., Wittfeld, K., Vuoksimaa, E., Xia, R., Yaffe, K., Yu, L., Zare, H., Zhao, W., Ames, D., Attia, J., Bennett, D.A., Brodaty, H., Chasman, D.I., Goldman, A.L., Hayward, C., Ikram, M.A., Jukema, J.W., Kardia, S.L.R., Lencz, T., Loeffler, M., Mattay, V.S., Palotie, A., Psaty, B.M., Ramirez, A., Ridker, P.M., Riedel-Heller, S.G., Sachdev, P.S., Saykin, A.J., Scherer, M., Schofield, P.R., Sidney, S., Starr, J.M., Trollor, J., Ulrich, W., Wagner, M., Weir, D.R., Wilson, J.F., Wright, M.J., Weinberger, D.R., Debette, S., Eriksson, J.G., Mosley, T.H., Launer, L.J., van Duijn, C.M., Deary, I.J., Seshadri, S., and Räikkönen, K.
- Abstract
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
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- 2022
24. Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts
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Silventoinen, K, Li, W, Jelenkovic, A, Sund, R, Yokoyama, Y, Aaltonen, S, Piirtola, M, Sugawara, M, Tanaka, M, Matsumoto, S, Baker, LA, Tuvblad, C, Tynelius, P, Rasmussen, F, Craig, JM, Saffery, R, Willemsen, G, Bartels, M, van Beijsterveldt, CEM, Martin, NG, Medland, SE, Montgomery, GW, Lichtenstein, P, Krueger, RF, McGue, M, Pahlen, S, Christensen, K, Skytthe, A, Kyvik, KO, Saudino, KJ, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Ullemar, V, Almqvist, C, Magnusson, PKE, Corley, RP, Huibregtse, BM, Knafo-Noam, A, Mankuta, D, Abramson, L, Haworth, CMA, Plomin, R, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Duncan, GE, Buchwald, D, Burt, SA, Klump, KL, Llewellyn, CH, Fisher, A, Boomsma, D, Sorensen, TIA, Kaprio, J, Silventoinen, K, Li, W, Jelenkovic, A, Sund, R, Yokoyama, Y, Aaltonen, S, Piirtola, M, Sugawara, M, Tanaka, M, Matsumoto, S, Baker, LA, Tuvblad, C, Tynelius, P, Rasmussen, F, Craig, JM, Saffery, R, Willemsen, G, Bartels, M, van Beijsterveldt, CEM, Martin, NG, Medland, SE, Montgomery, GW, Lichtenstein, P, Krueger, RF, McGue, M, Pahlen, S, Christensen, K, Skytthe, A, Kyvik, KO, Saudino, KJ, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Ullemar, V, Almqvist, C, Magnusson, PKE, Corley, RP, Huibregtse, BM, Knafo-Noam, A, Mankuta, D, Abramson, L, Haworth, CMA, Plomin, R, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Duncan, GE, Buchwald, D, Burt, SA, Klump, KL, Llewellyn, CH, Fisher, A, Boomsma, D, Sorensen, TIA, and Kaprio, J
- Abstract
BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.
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- 2022
25. Smoking remains associated with education after controlling for social background and genetic factors in a study of 18 twin cohorts
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Silventoinen, K, Piirtola, M, Jelenkovic, A, Sund, R, Tarnoki, AD, Tarnoki, DL, Medda, E, Nistico, L, Toccaceli, V, Honda, C, Inui, F, Tomizawa, R, Watanabe, M, Sakai, N, Gatz, M, Butler, DA, Lee, J, Lee, SJ, Sung, J, Franz, CE, Kremen, WS, Lyons, MJ, Derom, CA, Vlietinck, RF, Loos, RJF, Tynelius, P, Rasmussen, F, Martin, NG, Medland, SE, Montgomery, GW, Brandt, I, Nilsen, TS, Harris, JR, Tyler, J, Hopper, JL, Magnusson, PKE, Pedersen, NL, Aslan, AKD, Ordonana, JR, Sanchez-Romera, JF, Colodro-Conde, L, Rebato, E, Zhang, D, Pang, Z, Tan, Q, Silberg, JL, Maes, HH, Boomsma, D, Sorensen, TIA, Korhonen, T, Kaprio, J, Silventoinen, K, Piirtola, M, Jelenkovic, A, Sund, R, Tarnoki, AD, Tarnoki, DL, Medda, E, Nistico, L, Toccaceli, V, Honda, C, Inui, F, Tomizawa, R, Watanabe, M, Sakai, N, Gatz, M, Butler, DA, Lee, J, Lee, SJ, Sung, J, Franz, CE, Kremen, WS, Lyons, MJ, Derom, CA, Vlietinck, RF, Loos, RJF, Tynelius, P, Rasmussen, F, Martin, NG, Medland, SE, Montgomery, GW, Brandt, I, Nilsen, TS, Harris, JR, Tyler, J, Hopper, JL, Magnusson, PKE, Pedersen, NL, Aslan, AKD, Ordonana, JR, Sanchez-Romera, JF, Colodro-Conde, L, Rebato, E, Zhang, D, Pang, Z, Tan, Q, Silberg, JL, Maes, HH, Boomsma, D, Sorensen, TIA, Korhonen, T, and Kaprio, J
- Abstract
We tested the causality between education and smoking using the natural experiment of discordant twin pairs allowing to optimally control for background genetic and childhood social factors. Data from 18 cohorts including 10,527 monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs discordant for education and smoking were analyzed by linear fixed effects regression models. Within twin pairs, education levels were lower among the currently smoking than among the never smoking co-twins and this education difference was larger within DZ than MZ pairs. Similarly, education levels were higher among former smoking than among currently smoking co-twins, and this difference was larger within DZ pairs. Our results support the hypothesis of a causal effect of education on both current smoking status and smoking cessation. However, the even greater intra-pair differences within DZ pairs, who share only 50% of their segregating genes, provide evidence that shared genetic factors also contribute to these associations.
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- 2022
26. A saturated map of common genetic variants associated with human height
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Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN
- Abstract
Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
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- 2022
27. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning
- Author
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Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, Raikkonen, K, Lahti, J, Tuominen, S, Yang, Q, Pergola, G, Ahmad, S, Amin, N, Armstrong, NJ, Beiser, A, Bey, K, Bis, JC, Boerwinkle, E, Bressler, J, Campbell, A, Campbell, H, Chen, Q, Corley, J, Cox, SR, Davies, G, De Jager, PL, Derks, EM, Faul, JD, Fitzpatrick, AL, Fohner, AE, Ford, I, Fornage, M, Gerring, Z, Grabe, HJ, Grodstein, F, Gudnason, V, Simonsick, E, Holliday, EG, Joshi, PK, Kajantie, E, Kaprio, J, Karell, P, Kleineidam, L, Knol, MJ, Kochan, NA, Kwok, JB, Leber, M, Lam, M, Lee, T, Li, S, Loukola, A, Luck, T, Marioni, RE, Mather, KA, Medland, S, Mirza, SS, Nalls, MA, Nho, K, O'Donnell, A, Oldmeadow, C, Painter, J, Pattie, A, Reppermund, S, Risacher, SL, Rose, RJ, Sadashivaiah, V, Scholz, M, Satizabal, CL, Schofield, PW, Schraut, KE, Scott, RJ, Simino, J, Smith, AV, Smith, JA, Stott, DJ, Surakka, I, Teumer, A, Thalamuthu, A, Trompet, S, Turner, ST, van der Lee, SJ, Villringer, A, Voelker, U, Wilson, RS, Wittfeld, K, Vuoksimaa, E, Xia, R, Yaffe, K, Yu, L, Zare, H, Zhao, W, Ames, D, Attia, J, Bennett, DA, Brodaty, H, Chasman, DI, Goldman, AL, Hayward, C, Ikram, MA, Jukema, JW, Kardia, SLR, Lencz, T, Loeffler, M, Mattay, VS, Palotie, A, Psaty, BM, Ramirez, A, Ridker, PM, Riedel-Heller, SG, Sachdev, PS, Saykin, AJ, Scherer, M, Schofield, PR, Sidney, S, Starr, JM, Trollor, J, Ulrich, W, Wagner, M, Weir, DR, Wilson, JF, Wright, MJ, Weinberger, DR, Debette, S, Eriksson, JG, Mosley, TH, Launer, LJ, van Duijn, CM, Deary, IJ, Seshadri, S, and Raikkonen, K
- Abstract
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.
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- 2022
28. Physical activity and health:findings from Finnish monozygotic twin pairs discordant for physical activity
- Author
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Kujala, U. M. (Urho M.), Leskinen, T. (Tuija), Rottensteiner, M. (Mirva), Aaltonen, S. (Sari), Ala-Korpela, M. (Mika), Waller, K. (Katja), Kaprio, J. (Jaakko), Kujala, U. M. (Urho M.), Leskinen, T. (Tuija), Rottensteiner, M. (Mirva), Aaltonen, S. (Sari), Ala-Korpela, M. (Mika), Waller, K. (Katja), and Kaprio, J. (Jaakko)
- Abstract
Genetic and early environmental differences including early health habits associate with future health. To provide insight on the causal nature of these associations, monozygotic (MZ) twin pairs discordant for health habits provide an interesting natural experiment. Twin pairs discordant for leisure-time physical activity (LTPA) in early adult life is thus a powerful study design to investigate the associations between long-term LTPA and indicators of health and wellbeing. We have identified 17 LTPA discordant twin pairs from two Finnish twin cohorts and summarize key findings of these studies in this paper. The carefully characterized rare long-term LTPA discordant MZ twin pairs have participated in multi-dimensional clinical examinations. Key findings highlight that compared with less active twins in such MZ twin pairs, the twins with higher long-term LTPA have higher physical fitness, reduced body fat, reduced visceral fat, reduced liver fat, increased lumen diameters of conduit arteries to the lower limbs, increased bone mineral density in loaded bone areas, and an increased number of large high-density lipoprotein particles. The findings increase our understanding on the possible site-specific and system-level effects of long-term LTPA.
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- 2022
29. Genome-wide association meta-analysis of childhood and adolescent internalizing symptoms
- Author
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Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), Middeldorp, C. M. (Christel M.), Jami, E. S. (Eshim S.), Hammerschlag, A. R. (Anke R.), Ip, H. F. (Hill F.), Allegrini, A. G. (Andrea G.), Benyamin, B. (Beben), Border, R. (Richard), Diemer, E. W. (Elizabeth W.), Jiang, C. (Chang), Karhunen, V. (Ville), Lu, Y. (Yi), Lu, Q. (Qing), Mallard, T. T. (Travis T.), Mishra, P. P. (Pashupati P.), Nolte, I. M. (Ilja M.), Palviainen, T. (Teemu), Peterson, R. E. (Roseann E.), Sallis, H. M. (Hannah M.), Shabalin, A. A. (Andrey A.), Tate, A. E. (Ashley E.), Thiering, E. (Elisabeth), Vilor-Tejedor, N. (Natalia), Wang, C. (Carol), Zhou, A. (Ang), Adkins, D. E. (Daniel E.), Alemany, S. (Silvia), Ask, H. (Helga), Chen, Q. (Qi), Corley, R. P. (Robin P.), Ehli, E. A. (Erik A.), Evans, L. M. (Luke M.), Havdahl, A. (Alexandra), Hagenbeek, F. A. (Fiona A.), Hakulinen, C. (Christian), Henders, A. K. (Anjali K.), Hottenga, J. J. (Jouke Jan), Korhonen, T. (Tellervo), Mamun, A. (Abdullah), Marrington, S. (Shelby), Neumann, A. (Alexander), Rimfeld, K. (Kaili), Rivadeneira, F. (Fernando), Silberg, J. L. (Judy L.), van Beijsterveldt, C. E. (Catharina E.), Vuoksimaa, E. (Eero), Whipp, A. M. (Alyce M.), Tong, X. (Xiaoran), Andreassen, O. A. (Ole A.), Boomsma, D. I. (Dorret, I), Brown, S. A. (Sandra A.), Burt, S. A. (S. Alexandra), Copeland, W. (William), Dick, D. M. (Danielle M.), Harden, K. P. (K. Paige), Harris, K. M. (Kathleen Mullan), Hartman, C. A. (Catharina A.), Heinrich, J. (Joachim), Hewitt, J. K. (John K.), Hopfer, C. (Christian), Hypponen, E. (Elina), Järvelin, M.-R. (Marjo-Riitta), Kaprio, J. (Jaakko), Keltikangas-Jarvinen, L. (Liisa), Klump, K. L. (Kelly L.), Krauter, K. (Kenneth), Kuja-Halkola, R. (Ralf), Larsson, H. (Henrik), Lehtimaki, T. (Terho), Lichtenstein, P. (Paul), Lundstrom, S. (Sebastian), Maes, H. H. (Hermine H.), Magnus, P. (Per), Munafo, M. R. (Marcus R.), Najman, J. M. (Jake M.), Njolstad, P. R. (Pal R.), Oldehinkel, A. J. (Albertine J.), Pennell, C. E. (Craig E.), Plomin, R. (Robert), Reichborn-Kjennerud, T. (Ted), Reynolds, C. (Chandra), Rose, R. J. (Richard J.), Smolen, A. (Andrew), Snieder, H. (Harold), Stallings, M. (Michael), Standl, M. (Marie), Sunyer, J. (Jordi), Tiemeier, H. (Henning), Wadsworth, S. J. (Sally J.), Wall, T. L. (Tamara L.), Whitehouse, A. J. (Andrew J. O.), Williams, G. M. (Gail M.), Ystrom, E. (Eivind), Nivard, M. G. (Michel G.), Bartels, M. (Meike), and Middeldorp, C. M. (Christel M.)
- Abstract
Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84–2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%–8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| < 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42–0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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- 2022
30. Genetic architecture of motives for leisure‐time physical activity: a twin study
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Aaltonen, S., Kaprio, J., Vuoksimaa, E., Huppertz, C., Kujala, U. M., and Silventoinen, K.
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- 2017
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31. Mobility and muscle strength in male former elite endurance and power athletes aged 66−91 years
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Manderoos, S., Wasenius, N., Laine, M. K., Kujala, U. M., Mälkiä, E., Kaprio, J., Sarna, S., Bäckmand, H. M., Kettunen, J. A., Heinonen, O. J., Jula, A. M., Aunola, S., and Eriksson, J. G.
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- 2017
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32. Cohort Profile: The transition from childhood to adolescence in European children–how I.Family extends the IDEFICS cohort
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Ahrens, W, Siani, A, Adan, R, De Henauw, S, Eiben, G, Gwozdz, W, Hebestreit, A, Hunsberger, M, Kaprio, J, Krogh, V, Lissner, L, Molnár, D, Moreno, L A, Page, A, Picó, C, Reisch, L, Smith, R M, Tornaritis, M, Veidebaum, T, Williams, G, Pohlabeln, H, and Pigeot, I
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- 2017
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33. The effects of parental education on exercise behavior in childhood and youth: a study in Dutch and Finnish twins
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Huppertz, C., Bartels, M., de Geus, E. J. C., van Beijsterveldt, C. E. M., Rose, R. J., Kaprio, J., and Silventoinen, K.
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- 2017
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34. Prospective association between tobacco smoking and death by suicide: a competing risks hazard analysis in a large twin cohort with 35-year follow-up
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Evins, A. E., Korhonen, T., Kinnunen, T. H., and Kaprio, J.
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- 2017
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35. Liikemittarilla mitatun fyysisen aktiivisuuden yhteys itseraportoituihin liikkumisvaikeuksiin suomalaisilla kaksosilla
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Pullinen, P., Parkkari, J., Kaprio, J., Vähä-Ypyä, H., Sievänen, H., Kujala, U., and Waller, K.
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kaksostutkimus ,liikuntakyky ,ikääntyneet ,fyysinen aktiivisuus ,askelmittarit - Abstract
nonPeerReviewed
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- 2022
36. Bruxism Is Associated With Nicotine Dependence : A Nationwide Finnish Twin Cohort Study
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Rintakoski, K., Ahlberg, J., Hublin, C., Broms, U., Madden, P. A. F., Könönen, M., Koskenvuo, M., Lobbezoo, F., and Kaprio, J.
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- 2010
37. Tobacco use and reported bruxism in young adults : A nationwide Finnish Twin Cohort Study
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Rintakoski, K., Ahlberg, J., Hublin, C., Lobbezoo, F., Rose, R. J., Murtomaa, H., and Kaprio, J.
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- 2010
38. Genetic influences on adult body mass index followed over 29 years and their effects on late-life mobility: a study of twin sisters
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Ortega-Alonso, A, Sipilä, S, Kujala, U M, Kaprio, J, and Rantanen, T
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- 2009
39. Adipocyte morphology and implications for metabolic derangements in acquired obesity
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Heinonen, S, Saarinen, L, Naukkarinen, J, Rodríguez, A, Frühbeck, G, Hakkarainen, A, Lundbom, J, Lundbom, N, Vuolteenaho, K, Moilanen, E, Arner, P, Hautaniemi, S, Suomalainen, A, Kaprio, J, Rissanen, A, and Pietiläinen, K H
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- 2014
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40. Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample
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Loukola, A, Wedenoja, J, Keskitalo-Vuokko, K, Broms, U, Korhonen, T, Ripatti, S, Sarin, A-P, Pitkäniemi, J, He, L, Häppölä, A, Heikkilä, K, Chou, Y-L, Pergadia, M L, Heath, A C, Montgomery, G W, Martin, N G, Madden, P A F, and Kaprio, J
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- 2014
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41. Characterising metabolically healthy obesity in weight-discordant monozygotic twins
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Naukkarinen, J., Heinonen, S., Hakkarainen, A., Lundbom, J., Vuolteenaho, K., Saarinen, L., Hautaniemi, S., Rodriguez, A., Frühbeck, G., Pajunen, P., Hyötyläinen, T., Orešič, M., Moilanen, E., Suomalainen, A., Lundbom, N., Kaprio, J., Rissanen, A., and Pietiläinen, K. H.
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- 2014
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42. Voxel-based morphometry study on monozygotic twins discordant for Alzheimer's disease
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Rossi, R., Pievani, M., Järvenpää, T., Testa, C., Koskenvuo, M., Räihä, I., Kaprio, J., Frisoni, G. B., Rinne, J. O., and Laakso, M. P.
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- 2016
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43. Former male elite athletes have better metabolic health in late life than their controls
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Laine, M. K., Eriksson, J. G., Kujala, U. M., Kaprio, J., Loo, B.-M., Sundvall, J., Bäckmand, H. M., Peltonen, M., Jula, A., and Sarna, S.
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- 2016
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44. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
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Bryois, J. Skene, N.G. Hansen, T.F. Kogelman, L.J.A. Watson, H.J. Liu, Z. Adan, R. Alfredsson, L. Ando, T. Andreassen, O. Baker, J. Bergen, A. Berrettini, W. Birgegård, A. Boden, J. Boehm, I. Boni, C. Boraska Perica, V. Brandt, H. Breen, G. Bryois, J. Buehren, K. Bulik, C. Burghardt, R. Cassina, M. Cichon, S. Clementi, M. Coleman, J. Cone, R. Courtet, P. Crawford, S. Crow, S. Crowley, J. Danner, U. Davis, O. de Zwaan, M. Dedoussis, G. Degortes, D. DeSocio, J. Dick, D. Dikeos, D. Dina, C. Dmitrzak-Weglarz, M. Docampo Martinez, E. Duncan, L. Egberts, K. Ehrlich, S. Escaramís, G. Esko, T. Estivill, X. Farmer, A. Favaro, A. Fernández-Aranda, F. Fichter, M. Fischer, K. Föcker, M. Foretova, L. Forstner, A. Forzan, M. Franklin, C. Gallinger, S. Gaspar, H. Giegling, I. Giuranna, J. Giusti-Rodríquez, P. Gonidakis, F. Gordon, S. Gorwood, P. Gratacos Mayora, M. Grove, J. Guillaume, S. Guo, Y. Hakonarson, H. Halmi, K. Hanscombe, K. Hatzikotoulas, K. Hauser, J. Hebebrand, J. Helder, S. Henders, A. Herms, S. Herpertz-Dahlmann, B. Herzog, W. Hinney, A. Horwood, L.J. Hübel, C. Huckins, L. Hudson, J. Imgart, H. Inoko, H. Janout, V. Jiménez-Murcia, S. Johnson, C. Jordan, J. Julià, A. Juréus, A. Kalsi, G. Kaminská, D. Kaplan, A. Kaprio, J. Karhunen, L. Karwautz, A. Kas, M. Kaye, W. Kennedy, J. Kennedy, M. Keski-Rahkonen, A. Kiezebrink, K. Kim, Y.-R. Kirk, K. Klareskog, L. Klump, K. Knudsen, G.P. La Via, M. Landén, M. Larsen, J. Le Hellard, S. Leppä, V. Levitan, R. Li, D. Lichtenstein, P. Lilenfeld, L. Lin, B.D. Lissowska, J. Luykx, J. Magistretti, P. Maj, M. Mannik, K. Marsal, S. Marshall, C. Martin, N. Mattheisen, M. Mattingsdal, M. McDevitt, S. McGuffin, P. Medland, S. Metspalu, A. Meulenbelt, I. Micali, N. Mitchell, J. Mitchell, K. Monteleone, P. Monteleone, A.M. Montgomery, G. Mortensen, P.B. Munn-Chernoff, M. Nacmias, B. Navratilova, M. Norring, C. Ntalla, I. Olsen, C. Ophoff, R. O’Toole, J. Padyukov, L. Palotie, A. Pantel, J. Papezova, H. Parker, R. Pearson, J. Pedersen, N. Petersen, L. Pinto, D. Purves, K. Rabionet, R. Raevuori, A. Ramoz, N. Reichborn-Kjennerud, T. Ricca, V. Ripatti, S. Ripke, S. Ritschel, F. Roberts, M. Rotondo, A. Rujescu, D. Rybakowski, F. Santonastaso, P. Scherag, A. Scherer, S. Schmidt, U. Schork, N. Schosser, A. Seitz, J. Slachtova, L. Slagboom, P.E. Slof-Op ‘t Landt, M. Slopien, A. Sorbi, S. Strober, M. Stuber, G. Sullivan, P. Świątkowska, B. Szatkiewicz, J. Tachmazidou, I. Tenconi, E. Thornton, L. Tortorella, A. Tozzi, F. Treasure, J. Tsitsika, A. Tyszkiewicz-Nwafor, M. Tziouvas, K. van Elburg, A. van Furth, E. Wade, T. Wagner, G. Walton, E. Watson, H. Werge, T. Whiteman, D. Widen, E. Woodside, D.B. Yao, S. Yilmaz, Z. Zeggini, E. Zerwas, S. Zipfel, S. Anttila, V. Artto, V. Belin, A.C. de Boer, I. Boomsma, D.I. Børte, S. Chasman, D.I. Cherkas, L. Christensen, A.F. Cormand, B. Cuenca-Leon, E. Davey-Smith, G. Dichgans, M. van Duijn, C. Esko, T. Esserlind, A.L. Ferrari, M. Frants, R.R. Freilinger, T. Furlotte, N. Gormley, P. Griffiths, L. Hamalainen, E. Hiekkala, M. Ikram, M.A. Ingason, A. Järvelin, M.-R. Kajanne, R. Kallela, M. Kaprio, J. Kaunisto, M. Kogelman, L.J.A. Kubisch, C. Kurki, M. Kurth, T. Launer, L. Lehtimaki, T. Lessel, D. Ligthart, L. Litterman, N. Maagdenberg, A. Macaya, A. Malik, R. Mangino, M. McMahon, G. Muller-Myhsok, B. Neale, B.M. Northover, C. Nyholt, D.R. Olesen, J. Palotie, A. Palta, P. Pedersen, L. Pedersen, N. Posthuma, D. Pozo-Rosich, P. Pressman, A. Raitakari, O. Schürks, M. Sintas, C. Stefansson, K. Stefansson, H. Steinberg, S. Strachan, D. Terwindt, G. Vila-Pueyo, M. Wessman, M. Winsvold, B.S. Zhao, H. Zwart, J.A. Agee, M. Alipanahi, B. Auton, A. Bell, R. Bryc, K. Elson, S. Fontanillas, P. Furlotte, N. Heilbron, K. Hinds, D. Huber, K. Kleinman, A. Litterman, N. McCreight, J. McIntyre, M. Mountain, J. Noblin, E. Northover, C. Pitts, S. Sathirapongsasuti, J. Sazonova, O. Shelton, J. Shringarpure, S. Tian, C. Tung, J. Vacic, V. Wilson, C. Brueggeman, L. Bulik, C.M. Arenas, E. Hjerling-Leffler, J. Sullivan, P.F. International Headache Genetics Consortium Eating Disorders Working Group of the Psychiatric Genomics Consortium
- Abstract
Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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- 2020
45. Migration and Mortality: A 20 Year Follow up of Finnish Twin Pairs with Migrant Co-Twins in Sweden
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Hammar, N., Kaprio, J., Hagström, U., Alfredsson, L., Koskenvuo, M., and Hammar, T.
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- 2002
46. Cigarette Smoking, Alcohol Intoxication and Major Depressive Episode in a Representative Population Sample
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Hämäläinen, J., Kaprio, J., Isometsä, E., Heikkinen, M., Poikolainen, K., Lindeman, S., and Aro, H.
- Published
- 2001
47. Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa
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Huckins, L M, Hatzikotoulas, K, Southam, L, Thornton, L M, Steinberg, J, Aguilera-McKay, F, Treasure, J, Schmidt, U, Gunasinghe, C, Romero, A, Curtis, C, Rhodes, D, Moens, J, Kalsi, G, Dempster, D, Leung, R, Keohane, A, Burghardt, R, Ehrlich, S, Hebebrand, J, Hinney, A, Ludolph, A, Walton, E, Deloukas, P, Hofman, A, Palotie, A, Palta, P, van Rooij, F J A, Stirrups, K, Adan, R, Boni, C, Cone, R, Dedoussis, G, van Furth, E, Gonidakis, F, Gorwood, P, Hudson, J, Kaprio, J, Kas, M, Keski-Rahonen, A, Kiezebrink, K, Knudsen, G-P, Maj, M, Monteleone, A M, Monteleone, P, Raevuori, A H, Reichborn-Kjennerud, T, Tozzi, F, Tsitsika, A, van Elburg, A, Collier, D A, Sullivan, P F, Breen, G, Bulik, C M, and Zeggini, E
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- 2018
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48. Physically active vs. inactive lifestyle, muscle properties, and glucose homeostasis in middle-aged and older twins
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Leskinen, T., Sipilä, S., Kaprio, J., Kainulainen, H., Alen, M., and Kujala, U. M.
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- 2013
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49. Genetic and Environmental Correlations Between Body Mass Index and Waist Circumference in China: The Qingdao Adolescent Twin Study
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Ning, F., Silventoinen, K., Pang, Z. C., Kaprio, J., Wang, S. J., Zhang, D., Duan, H. P., Wu, W. F., and Qiao, Q.
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- 2013
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50. Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices
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Natarajan, P. (Pradeep), Pampana, A. (Akhil), Graham, S. E. (Sarah E.), Ruotsalainen, S. E. (Sanni E.), Perry, J. A. (James A.), de Vries, P. S. (Paul S.), Broome, J. G. (Jai G.), Pirruccello, J. P. (James P.), Honigbere, M. C. (Michael C.), Aragam, K. (Krishna), Wolford, B. (Brooke), Brody, J. A. (Jennifer A.), Antonacci-Fulton, L. (Lucinda), Arden, M. (Moscati), Aslibekyan, S. (Stella), Assimes, T. L. (Themistocles L.), Ballantyne, C. M. (Christie M.), Bielak, L. F. (Lawrence F.), Bisl, J. C. (Joshua C.), Cade, B. E. (Brian E.), Do, R. (Ron), Doddapaneni, H. (Harsha), Emery, L. S. (Leslie S.), Hung, Y.-J. (Yi-Jen), Irvin, M. R. (Marguerite R.), Khan, A. T. (Alyna T.), Lange, L. (Leslie), Lee, J. (Jiwon), Lemaitre, R. N. (Rozenn N.), Martin, L. W. (Lisa W.), Metcalf, G. (Ginger), Montasser, M. E. (May E.), Moon, J.-Y. (Jee-Young), Muzny, D. (Donna), Connell, J. R. (Jeffrey R. O.), Palmer, N. D. (Nicholette D.), Peralta, J. M. (Juan M.), Peyser, P. A. (Patricia A.), Stilp, A. M. (Adrienne M.), Tsai, M. (Michael), Wang, F. F. (Fei Fei), Weeks, D. E. (Daniel E.), Yanek, L. R. (Lisa R.), Wilson, J. G. (James G.), Abecasis, G. (Goncalo), Arnett, D. K. (Donna K.), Becker, L. C. (Lewis C.), Blangercy, J. (John), Boerwinkle, E. (Eric), Bowden, D. W. (Donald W.), Chang, Y.-C. (Yi-Cheng), Chen, Y. I. (Yii-Der, I), Choi, W. J. (Won Jung), Correa, A. (Adolfo), Curran, J. E. (Joanne E.), Daly, M. J. (Mark J.), DutcherE, S. K. (Susan K.), Ellinor, P. T. (Patrick T.), Fornage, M. (Myriam), Freedman, B. I. (Barry, I), Gabriel, S. (Stacey), Germer, S. (Soren), Gibbs, R. A. (Richard A.), He, J. (Jiang), Hveem, K. (Kristian), Jarvik, G. P. (Gail P.), Kaplan, R. C. (Robert C.), Kardia, S. L. (Sharon L. R.), Kennyn, E. (Eimear), Kim, R. W. (Ryan W.), Kooperberg, C. (Charles), Laurie, C. C. (Cathy C.), Lee, S. (Seonwook), Lloyd-Jones, D. M. (Don M.), Loos, R. J. (Ruth J. F.), Lubitz, S. A. (Steven A.), Mathias, R. A. (Rasika A.), Martinez, K. A. (Karine A. Viaud), McGarvey, S. T. 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- Subjects
Cardiovascular genetics ,Genome-wide association studies - Abstract
Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
- Published
- 2021
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