61 results on '"Adams H.H.H."'
Search Results
52. Heritability of the shape of subcortical brain structures in the general population
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Roshchupkin, G.V. (Gennady), Gutman, B.A. (Boris A.), Vernooij, M.W. (Meike), Jahanshad, N. (Neda), Martin, N.G. (Nicholas), Hofman, A. (Albert), Mcmahon, K.L. (Katie), Lee, S.J. (Sven) van der, Duijn, C.M. (Cornelia) van, Zubicaray, G.I. (Greig) de, Uitterlinden, A.G. (André), Wright, M.J. (Margaret), Niessen, W.J. (Wiro), Thompson, P.M. (Paul), Ikram, M.K. (Kamran), Adams, H.H.H. (Hieab), Roshchupkin, G.V. (Gennady), Gutman, B.A. (Boris A.), Vernooij, M.W. (Meike), Jahanshad, N. (Neda), Martin, N.G. (Nicholas), Hofman, A. (Albert), Mcmahon, K.L. (Katie), Lee, S.J. (Sven) van der, Duijn, C.M. (Cornelia) van, Zubicaray, G.I. (Greig) de, Uitterlinden, A.G. (André), Wright, M.J. (Margaret), Niessen, W.J. (Wiro), Thompson, P.M. (Paul), Ikram, M.K. (Kamran), and Adams, H.H.H. (Hieab)
- Abstract
The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures.
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- 2016
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53. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
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Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), Palotie, A. (Aarno), Gormley, A.M., Stefansson, H. (Hreinn), Winsvold, B.S. (Bendik), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune), Farh, K.-H. (Kai-How), Cuenca-Leon, E. (Ester), Muona, M. (Mikko), Furlotte, N.A. (Nicholas A.), Kurth, T. (Tobias), Ingason, A. (Andres), Mcmahon, G. (George), Ligthart, L. (Lannie), Terwindt, G.M. (Gisela), Todt, U. (Unda), Müller-Myhsok, B. (Bertram), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Göbel, H. (Hartmut), Koiranen, M. (Markku), Quaye, L. (Lydia), Adams, H.H.H. (Hieab H.H.), Lehtimäki, T. (Terho), Sarin, A.-P., Wedenoja, J. (Juho), Hinds, D.A. (David A.), Buring, J.E. (Julie E.), Schürks, M. (Markus), Ridker, P.M. (Paul), Hrafnsdottir, M.G. (Maria Gudlaug), Ring, S.M. (Susan), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Hämäläinen, E. (Eija), Lucae, S. (Susanne), Malik, R. (Rainer), Heath, A.C. (Andrew C.), Madden, P.A. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M.I. (Mitja I.), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jian), Stergiakouli, E. (Evangelia), Lee, P.H. (Phil), Sandor, C. (Cynthia), Webber, C. (Caleb), Cader, Z. (Zameel), Müller-Myhsok, B. (B.), Schreiber, S. (Stefan), Meitinger, T. (Thomas), Hagen, K. (Knut), Salomaa, V. (Veikko), Heikkilä, K. (Kauko), Loehrer, E. (Elizabeth), Uitterlinden, A.G. (André), Hofman, A. (Albert), Duijn, C.M. (Cornelia) van, Cherkas, L. (Lynn), Pedersen, L.M. (Linda M.), Stubhaug, A. (Audun), Nielsen, C.S. (Christopher S.), Männikkö, M. (Minna), Mihailov, E. (Evelin), Milani, L. (Lili), Esserlind, A.-L. (Ann-Louise), Christensen, A.F. (Anne Francke), Hansen, T.F. (Thomas Folkmann), Werge, T.M. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (Arfan), Ikram, M.K. (Kamran), Jarvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Strachan, D.P. (David), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), Maagdenberg, A.M.J.M. (Arn), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Smith, G.D. (George Davey), Stefansson, K. (Kari), Eriksson, N. (Nicholas), Daly, M.J. (Mark), Neale, B.M. (Benjamin), Olesen, J. (Jes), Chasman, D.I. (Daniel), Nyholt, D.R. (Dale), and Palotie, A. (Aarno)
- Abstract
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association (GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms (SNPs) significantly associated with migraine risk (P < 5 × 10-8) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.
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- 2016
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54. HASE: Framework for efficient high-dimensional association analyses
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Roshchupkin, G.V., primary, Adams, H.H.H., additional, Vernooij, M.W., additional, Hofman, A., additional, Van Duijn, C.M., additional, Ikram, M.A., additional, and Niessen, W.J., additional
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- 2016
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55. Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia
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Adams, H.H.H. (Hieab), Bruijn, R.F.A.G. (Renée) de, Hofman, A. (Albert), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Vernooij, M.W. (Meike), Koudstaal, P.J. (Peter), Ikram, M.A. (Arfan), Adams, H.H.H. (Hieab), Bruijn, R.F.A.G. (Renée) de, Hofman, A. (Albert), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Vernooij, M.W. (Meike), Koudstaal, P.J. (Peter), and Ikram, M.A. (Arfan)
- Abstract
Introduction Neurodegenerative diseases are a major cause of cognitive impairment and can ultimately lead to dementia. Genome-wide association studies have uncovered many genetic variants conferring risk of neurodegenerative diseases, but their role in cognitive impairment remains unexplored. Methods In the prospective, population-based Rotterdam Study, 3605 nondemented persons aged ≥55 years were genotyped, screened for mild cognitive impairment (MCI) in 2002 to 2005 and underwent continuous follow-up for dementia until 2012. Weighted polygenic risk scores of genetic variants for Alzheimer's disease (AD), Parkinson's disease (PD), and the frontotemporal lobar degeneration/amyotrophic lateral sclerosis disease spectrum (FTLD/ALS) were constructed and investigated for association with MCI and the subsequent conversion to dementia. Results In total, 360 (10.0%) persons had MCI, of whom 147 (4.1%) were amnestic and 213 (5.9%) nonamnestic. The AD risk score was associated with both MCI subtypes (odds ratio for all MCI 1.15 [95% CI, 1.03-1.28]), whereas PD and FTLD/ALS risk scores were associated only with nonamnestic MCI (odds ratios 1.15 [1.00-1.32] and 1.19 [1.03-1.37], respectively). The AD risk score, but not PD and FTLD/ALS risk scores, was associated with an increased risk of dementia (hazard ratio 1.55 [1.37-1.77]). Discussion Genetic evidence supports the view that multiple neurodegenerative pathways lead to MCI and that the subsequent conversion to dementia, primarily of the AD subtype, is mainly due to the AD pathway(s).
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- 2015
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56. Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium
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Davies, G. (Gail), Armstrong, N.J. (Nicola), Bis, J.C. (Joshua), Bressler, J. (Jan), Chouraki, V. (Vincent), Giddaluru, S. (Sudheer), Hofer, E., Ibrahim-Verbaas, C.A. (Carla), Kirin, M. (Mirna), Lahti, J., Lee, S.J. (Sven) van der, Le Hellard, S. (Stephanie), Liu, T., Marioni, R.E. (Riccardo), Oldmeadow, C. (Christopher), Postmus, D. (Douwe), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Thalamuthu, A. (Anbupalam), Thomson, R. (Russell), Vitart, V. (Veronique), Wang, J., Yu, L., Zgaga, L. (Lina), Zhao, W. (Wei), Boxall, R. (Ruth), Harris, S.E. (Sarah), Hill, W.D. (W. David), Liewald, D.C. (David C.), Luciano, M. (Michelle), Adams, H.H.H. (Hieab), Ames, D. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Assareh, A.A., Au, R., Becker, J.T. (James), Beiser, A., Berr, C. (Claudine), Bertram, L. (Lars), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Campbell, H. (Harry), Corley, J. (Janie), De Jager, P.L., Dufouil, C. (Carole), Eriksson, J.G. (Johan G.), Espeseth, T. (Thomas), Faul, J.D., Ford, I., Scotland, G. (Generation), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B., Heiss, G. (Gerardo), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Huffman, J.E. (Jennifer), Kardia, S.L.R. (Sharon), Kochan, N.A. (Nicole A.), Knopman, D.S. (David), Kwok, J.B., Lambert, J.-C., Lee, T., Li, G., Li, S.-C., Loitfelder, M. (Marisa), Lopez, O.L. (Oscar), Lundervold, A.J., Lundqvist, A., Mather, R., Mirza, S.S. (Saira), Nyberg, L., Oostra, B.A. (Ben), Palotie, A. (Aarno), Papenberg, G., Pattie, A. (Alison), Petrovic, K. (Katja), Polasek, O. (Ozren), Psaty, B.M. (Bruce), Redmond, P. (Paul), Reppermund, S., Rotter, J.I., Schmidt, R. (Reinhold), Schuur, M. (Maaike), Schofield, P.W., Scott, R.J., Steen, V.M. (Vidar), Stott, D.J. (David J.), Swieten, J.C. (John) van, Taylor, K.D. (Kent), Trollor, J., Trompet, S. (Stella), Uitterlinden, A.G. (André), Weinstein, G., Widen, E. (Elisabeth), Windham, B.G. (Gwen), Jukema, J.W. (Jan Wouter), Wright, A. (Alan), Wright, M.J. (Margaret), Yang, Q. (Qiong Fang), Amieva, H. (Hélène), Attia, J. (John), Bennett, D.A. (David), Brodaty, H. (Henry), Craen, A.J. (Anton) de, Hayward, C., Ikram, M.A. (Arfan), Lindenberger, U., Nilsson, L.-G., Porteous, D.J. (David J.), Räikkönen, K. (Katri), Reinvang, I. (Ivar), Rudan, I. (Igor), Sachdev, P.S. (Perminder), Schmidt, R., Schofield, P. (Peter), Srikanth, V., Starr, J.M. (John), Turner, S.T. (Stephen), Weir, D.R. (David R.), Wilson, J.F. (James F), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), Deary, I.J. (Ian), Davies, G. (Gail), Armstrong, N.J. (Nicola), Bis, J.C. (Joshua), Bressler, J. (Jan), Chouraki, V. (Vincent), Giddaluru, S. (Sudheer), Hofer, E., Ibrahim-Verbaas, C.A. (Carla), Kirin, M. (Mirna), Lahti, J., Lee, S.J. (Sven) van der, Le Hellard, S. (Stephanie), Liu, T., Marioni, R.E. (Riccardo), Oldmeadow, C. (Christopher), Postmus, D. (Douwe), Smith, A.V. (Davey), Smith, J.A. (Jennifer A), Thalamuthu, A. (Anbupalam), Thomson, R. (Russell), Vitart, V. (Veronique), Wang, J., Yu, L., Zgaga, L. (Lina), Zhao, W. (Wei), Boxall, R. (Ruth), Harris, S.E. (Sarah), Hill, W.D. (W. David), Liewald, D.C. (David C.), Luciano, M. (Michelle), Adams, H.H.H. (Hieab), Ames, D. (David), Amin, N. (Najaf), Amouyel, P. (Philippe), Assareh, A.A., Au, R., Becker, J.T. (James), Beiser, A., Berr, C. (Claudine), Bertram, L. (Lars), Boerwinkle, E.A. (Eric), Buckley, B.M. (Brendan M.), Campbell, H. (Harry), Corley, J. (Janie), De Jager, P.L., Dufouil, C. (Carole), Eriksson, J.G. (Johan G.), Espeseth, T. (Thomas), Faul, J.D., Ford, I., Scotland, G. (Generation), Gottesman, R.F. (Rebecca), Griswold, M.D. (Michael), Gudnason, V. (Vilmundur), Harris, T.B., Heiss, G. (Gerardo), Hofman, A. (Albert), Holliday, E.G. (Elizabeth), Huffman, J.E. (Jennifer), Kardia, S.L.R. (Sharon), Kochan, N.A. (Nicole A.), Knopman, D.S. (David), Kwok, J.B., Lambert, J.-C., Lee, T., Li, G., Li, S.-C., Loitfelder, M. (Marisa), Lopez, O.L. (Oscar), Lundervold, A.J., Lundqvist, A., Mather, R., Mirza, S.S. (Saira), Nyberg, L., Oostra, B.A. (Ben), Palotie, A. (Aarno), Papenberg, G., Pattie, A. (Alison), Petrovic, K. (Katja), Polasek, O. (Ozren), Psaty, B.M. (Bruce), Redmond, P. (Paul), Reppermund, S., Rotter, J.I., Schmidt, R. (Reinhold), Schuur, M. (Maaike), Schofield, P.W., Scott, R.J., Steen, V.M. (Vidar), Stott, D.J. (David J.), Swieten, J.C. (John) van, Taylor, K.D. (Kent), Trollor, J., Trompet, S. (Stella), Uitterlinden, A.G. (André), Weinstein, G., Widen, E. (Elisabeth), Windham, B.G. (Gwen), Jukema, J.W. (Jan Wouter), Wright, A. (Alan), Wright, M.J. (Margaret), Yang, Q. (Qiong Fang), Amieva, H. (Hélène), Attia, J. (John), Bennett, D.A. (David), Brodaty, H. (Henry), Craen, A.J. (Anton) de, Hayward, C., Ikram, M.A. (Arfan), Lindenberger, U., Nilsson, L.-G., Porteous, D.J. (David J.), Räikkönen, K. (Katri), Reinvang, I. (Ivar), Rudan, I. (Igor), Sachdev, P.S. (Perminder), Schmidt, R., Schofield, P. (Peter), Srikanth, V., Starr, J.M. (John), Turner, S.T. (Stephen), Weir, D.R. (David R.), Wilson, J.F. (James F), Duijn, C.M. (Cornelia) van, Launer, L.J. (Lenore), Fitzpatrick, A.L. (Annette), Seshadri, S. (Sudha), Mosley, T.H. (Thomas H.), and Deary, I.J. (Ian)
- Abstract
General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10-9, MIR2113; rs17522122, P=2.55 × 10-8, AKAP6; rs10119, P=5.67 × 10-9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10-6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ∼1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10-17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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- 2015
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57. White Matter Lesion Progression: Genome-Wide Search for Genetic Influences
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Hofer, E. (Edith), Cavalieri, M. (Margherita), Bis, J.C. (Joshua), DeCarli, C. (Charles), Fornage, M. (Myriam), Sigurdsson, S. (Sigurdur), Srikanth, V. (Velandai), Trompet, S. (Stella), Verhaaren, B.F.J. (Benjamin), Wolf, C. (Christiane), Yang, Q. (Qiong Fang), Adams, H.H.H. (Hieab), Amouyel, P. (Philippe), Beiser, A. (Alexa), Buckley, B.M. (Brendan M.), Callisaya, M. (Michele), Chauhan, G. (Ganesh), De Craen, A.J.M. (Anton J. M.), Dufouil, C. (Carole), Duijn, C.M. (Cornelia) van, Ford, I., Freudenberger, P. (Paul), Gottesman, R.F. (Rebecca), Gudnason, V. (Vilmundur), Heiss, G. (Gerardo), Hofman, A. (Albert), Lumley, T. (Thomas), Martinez, O. (Oliver), Mazoyer, B. (Bernard), Moran, C. (Chris), Niessen, W.J. (Wiro), Phan, T.G. (Thanh), Psaty, B.M. (Bruce), Satizabal, C.L. (Claudia), Sattar, N. (Naveed), Schilling, S. (Sabrina), Shibata, D.K. (Dean), Slagboom, P.E. (Eline), Smith, A.V. (Davey), Stott, D.J. (David. J.), Taylor, K.D. (Kent), Thomson, R. (Russell), Töglhofer, A.M. (Anna Maria), Tzourio, C. (Christophe), Buchem, M.A. (Mark) van, Wang, J. (Jing), Westendorp, R.G.J. (Rudi), Windham, B.G. (Gwen), Vernooij, M.W. (Meike), Zijdenbos, A.P., Beare, R.J. (Richard), Debette, S. (Stéphanie), Ikram, M.A. (Arfan), Jukema, J.W. (Jan Wouter), Launer, L.J. (Lenore), Longstreth Jr, W.T., Mosley, T.H. (Thomas H.), Seshadri, S. (Sudha), Schmidt, R. (Reinhold), Hofer, E. (Edith), Cavalieri, M. (Margherita), Bis, J.C. (Joshua), DeCarli, C. (Charles), Fornage, M. (Myriam), Sigurdsson, S. (Sigurdur), Srikanth, V. (Velandai), Trompet, S. (Stella), Verhaaren, B.F.J. (Benjamin), Wolf, C. (Christiane), Yang, Q. (Qiong Fang), Adams, H.H.H. (Hieab), Amouyel, P. (Philippe), Beiser, A. (Alexa), Buckley, B.M. (Brendan M.), Callisaya, M. (Michele), Chauhan, G. (Ganesh), De Craen, A.J.M. (Anton J. M.), Dufouil, C. (Carole), Duijn, C.M. (Cornelia) van, Ford, I., Freudenberger, P. (Paul), Gottesman, R.F. (Rebecca), Gudnason, V. (Vilmundur), Heiss, G. (Gerardo), Hofman, A. (Albert), Lumley, T. (Thomas), Martinez, O. (Oliver), Mazoyer, B. (Bernard), Moran, C. (Chris), Niessen, W.J. (Wiro), Phan, T.G. (Thanh), Psaty, B.M. (Bruce), Satizabal, C.L. (Claudia), Sattar, N. (Naveed), Schilling, S. (Sabrina), Shibata, D.K. (Dean), Slagboom, P.E. (Eline), Smith, A.V. (Davey), Stott, D.J. (David. J.), Taylor, K.D. (Kent), Thomson, R. (Russell), Töglhofer, A.M. (Anna Maria), Tzourio, C. (Christophe), Buchem, M.A. (Mark) van, Wang, J. (Jing), Westendorp, R.G.J. (Rudi), Windham, B.G. (Gwen), Vernooij, M.W. (Meike), Zijdenbos, A.P., Beare, R.J. (Richard), Debette, S. (Stéphanie), Ikram, M.A. (Arfan), Jukema, J.W. (Jan Wouter), Launer, L.J. (Lenore), Longstreth Jr, W.T., Mosley, T.H. (Thomas H.), Seshadri, S. (Sudha), and Schmidt, R. (Reinhold)
- Abstract
Background and Purpose-White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods-Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. Results-A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no single-nucleotide polymorphisms achieved genome-wide significance (P<5×10-8). Four loci were suggestive (P<1×10-5) of an association with WML progression: 10q24.32 (rs10883817, P=1.46×10-6); 12q13.13 (rs4
- Published
- 2015
- Full Text
- View/download PDF
58. Common genetic variants influence human subcortical brain structures
- Author
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Hibar, D.P. (Derrek), Stein, J.L., Rentería, M.E. (Miguel), Arias-Vásquez, A. (Alejandro), Desrivières, S. (Sylvane), Jahanshad, N. (Neda), Toro, R. (Roberto), Wittfeld, K. (Katharina), Abramovic, L. (Lucija), Andersson, M. (Micael), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Bernard, M. (Manon), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brown, A.A. (Andrew), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Cuellar-Partida, G. (Gabriel), Braber, A. (Anouk) den, Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Grimm, O. (Oliver), Guadalupe, T. (Tulio), Hass, J. (Johanna), Woldehawariat, G. (Girma), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil H.), Olde Loohuis, L.M. (Loes M.), Luciano, M. (Michelle), MacAre, C. (Christine), Mather, R., Mattheisen, M. (Manuel), Milaneschi, Y. (Yuri), Nho, K. (Kwangsik), Papmeyer, M. (Martina), Ramasamy, A. (Adaikalavan), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rose, E.J. (Emma), Salami, A. (Alireza), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shin, J. (Jean), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Walters, R.K. (Raymond), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Winkler, A.M. (Anderson), Zwiers, M.P. (Marcel), Alhusaini, S. (Saud), Athanasiu, L. (Lavinia), Ehrlich, S.M. (Stefan), Hakobjan, M. (Marina), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Heister, A.J.G.A.M. (Angelien J. G. A. M.), Hoehn, D. (David), Kasperaviciute, D. (Dalia), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Makkinje, R.R.R. (Remco R. R.), Matarin, M. (Mar), Naber, M.A.M. (Marlies A. M.), McKay, D.R. (Reese), Needham, M. (Margaret), Nugent, A.C. (Allison), Pütz, B. (Benno), Royle, N.A. (Natalie), Shen, L. (Li), Sprooten, R. (Roy), Trabzuni, D. (Danyah), Van Der Marel, S.S.L. (Saskia S. L.), Van Hulzen, K.J.E. (Kimm J. E.), Walton, E. (Esther), Björnsson, A. (Asgeir), Almasy, L. (Laura), Ames, D.J. (David), Arepalli, S. (Sampath), Assareh, A.A., Bastin, M.E. (Mark), Brodaty, H. (Henry), Bulayeva, K. (Kazima), Carless, M.A. (Melanie), Cichon, S. (Sven), Corvin, A. (Aiden), Curran, J.E. (Joanne), Czisch, M. (Michael), Zubicaray, G.I. (Greig) de, Dillman, A. (Allissa), Duggirala, A. (Aparna), Dyer, M.D. (Matthew), Erk, S., Fedko, I. (Iryna), Ferrucci, L. (Luigi), Foroud, T. (Tatiana), Fox, P.T. (Peter), Fukunaga, M. (Masaki), Raphael Gibbs, J., Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Guelfi, S. (Sebastian), Hansell, N.K. (Narelle), Hartman, C.A. (Catharina), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Hoekstra, P.J. (Pieter), Holsboer, F., Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Ikeda, M. (Masashi), Jack Jr., C.R. (Clifford), Jenkinson, S. (Sarah), Johnson, R. (Robert), Kanai, R. (Ryota), Keil, M. (Maria), Kent, J.W. (Jack W.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Mcmahon, K.L. (Katie), Meisenzahl, E. (Eva), Melle, I. (Ingrid), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant), Mostert, J.C. (Jeanette C.), Mühleisen, T.W. (Thomas), Nalls, M.A. (Michael), Nichols, T.E. (Thomas), Nilsson, L.G., Nöthen, M.M. (Markus), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Perez-Iglesias, R. (Rocio), Pike, G.B. (Bruce), Potkin, S.G. (Steven), Reinvang, I. (Ivar), Reppermund, S., Rietschel, M. (Marcella), Seiferth, N. (Nina), Rosen, G.D. (Glenn D.), Rujescu, D. (Dan), Schnell, K. (Kerry), Schofield, C.J. (Christopher), Smith, C. (Colin), Steen, V.M. (Vidar), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Turner, J. (Jessica), Valdés Hernández, M.C. (Maria), Ent, D. (Dennis) van 't, Brug, M.P. (Marcel) van der, Wee, N.J. (Nic) van der, Tol, M.J.D. (Marie-José) van, Veltman, D.J. (Dick), Wassink, A.M.J. (Annemarie), Westman, E. (Eric), Zielke, R.H. (Ronald H.), Zonderman, A.B. (Alan B.), Ashbrook, D.G. (David G.), Hager, R. (Reinmar), Lu, L. (Lu), Mcmahon, F.J. (Francis J), Morris, D.W. (Derek W), Williams, R.W. (Robert W.), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan K.), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cavalleri, G. (Gianpiero), Crespo-Facorro, B. (Benedicto), Dale, A.M. (Anders), Davies, G.E. (Gareth), Delanty, N., Depondt, C. (Chantal), Djurovic, S. (Srdjan), Drevets, D.A. (Douglas), Espeseth, T. (Thomas), Gollub, R.L. (Randy), Ho, B.C. (Beng ), Hoffmann, W. (Wolfgang), Hosten, N. (Norbert), Kahn, R. (René), Le Hellard, S. (Stephanie), Meyer-Lindenberg, A., Müller-Myhsok, B. (B.), Nauck, M. (Matthias), Nyberg, L. (Lars), Pandolfo, M. (Massimo), Penninx, B.W.J.H. (Brenda), Roffman, J.L. (Joshua), Sisodiya, S.M. (Sanjay), Smoller, J.W., Bokhoven, H. (Hans) van, Haren, N.E.M. (Neeltje E.) van, Völzke, H. (Henry), Walter, H.J. (Henrik), Weiner, M.W. (Michael), Wen, W. (Wei), White, T.J.H. (Tonya), Agartz, I. (Ingrid), Andreassen, O.A. (Ole), Blangero, J. (John), Boomsma, D.I. (Dorret), Brouwer, R.M. (Rachel), Cannon, D.M. (Dara), Cookson, M.R. (Mark), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Donohoe, D.J. (Dennis), Fernandez, G. (Guillén), Fisher, S.E. (Simon), Francks, C. (Clyde), Glahn, D.C. (David), Grabe, H.J. (Hans Jörgen), Gruber, O. (Oliver), Hardy, J. (John), Hashimoto, R. (Ryota), Hulshoff Pol, H.E. (Hilleke), Jönsson, E.G. (Erik), Kloszewska, I. (Iwona), Lovestone, S. (Simon), Mattay, V.S. (Venkata S.), Mecocci, P. (Patrizia), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Ophoff, R.A. (Roel), Paus, T. (Tomas), Pausova, Z. (Zdenka), Ryten, M. (Mina), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Simmons, A. (Andrew), Singleton, A. (Andrew), Soininen, H. (H.), Wardlaw, J.M. (J.), Weale, M.E. (Michael), Weinberger, D.R. (Daniel), Adams, H.H.H. (Hieab), Launer, L.J. (Lenore), Seiler, S. (Stephan), Schmidt, R. (Reinhold), Chauhan, G. (Ganesh), Satizabal, C.L. (Claudia), Becker, J.T. (James), Yanek, L.R. (Lisa), Lee, S.J. (Sven) van der, Ebling, M. (Maritza), Fischl, B. (Bruce), Longstreth Jr, W.T., Greve, D. (Douglas), Nyquist, P. (Paul), Vinke, L.N. (Louis N.), Duijn, C.M. (Cornelia) van, Xue, L. (Luting), Mazoyer, B. (Bernard), Bis, J.C. (Joshua), Gudnason, V. (Vilmundur), Seshadri, S. (Sudha), Ikram, M.A. (Arfan), Martin, N.G. (Nicholas), Wright, M.J. (Margaret), Schumann, G. (Gunter), Franke, B. (Barbara), Thompson, P.M. (Paul), Medland, S.E. (Sarah), Hibar, D.P. (Derrek), Stein, J.L., Rentería, M.E. (Miguel), Arias-Vásquez, A. (Alejandro), Desrivières, S. (Sylvane), Jahanshad, N. (Neda), Toro, R. (Roberto), Wittfeld, K. (Katharina), Abramovic, L. (Lucija), Andersson, M. (Micael), Aribisala, B. (Benjamin), Armstrong, N.J. (Nicola J.), Bernard, M. (Manon), Bohlken, M.M. (Marc M.), Boks, M.P.M. (Marco), Bralten, L.B.C. (Linda), Brown, A.A. (Andrew), Chakravarty, M.M. (M. Mallar), Chen, Q. (Qiang), Ching, C.R.K. (Christopher), Cuellar-Partida, G. (Gabriel), Braber, A. (Anouk) den, Giddaluru, S. (Sudheer), Goldman, A.L. (Aaron L.), Grimm, O. (Oliver), Guadalupe, T. (Tulio), Hass, J. (Johanna), Woldehawariat, G. (Girma), Holmes, A.J. (Avram), Hoogman, M. (Martine), Janowitz, D. (Deborah), Jia, T. (Tianye), Kim, S. (Shinseog), Klein, M. (Marieke), Kraemer, B. (Bernd), Lee, P.H. (Phil H.), Olde Loohuis, L.M. (Loes M.), Luciano, M. (Michelle), MacAre, C. (Christine), Mather, R., Mattheisen, M. (Manuel), Milaneschi, Y. (Yuri), Nho, K. (Kwangsik), Papmeyer, M. (Martina), Ramasamy, A. (Adaikalavan), Risacher, S.L. (Shannon), Roiz-Santiañez, R. (Roberto), Rose, E.J. (Emma), Salami, A. (Alireza), Sämann, P.G. (Philipp), Schmaal, L. (Lianne), Schork, N.J. (Nicholas), Shin, J. (Jean), Strike, L.T. (Lachlan), Teumer, A. (Alexander), Van Donkelaar, M.M.J. (Marjolein M. J.), Eijk, K.R. (Kristel) van, Walters, R.K. (Raymond), Westlye, L.T. (Lars), Whelan, C.D. (Christopher), Winkler, A.M. (Anderson), Zwiers, M.P. (Marcel), Alhusaini, S. (Saud), Athanasiu, L. (Lavinia), Ehrlich, S.M. (Stefan), Hakobjan, M. (Marina), Hartberg, C.B. (Cecilie B.), Haukvik, U.K. (Unn), Heister, A.J.G.A.M. (Angelien J. G. A. M.), Hoehn, D. (David), Kasperaviciute, D. (Dalia), Liewald, D.C.M. (David), Lopez, L.M. (Lorna), Makkinje, R.R.R. (Remco R. R.), Matarin, M. (Mar), Naber, M.A.M. (Marlies A. M.), McKay, D.R. (Reese), Needham, M. (Margaret), Nugent, A.C. (Allison), Pütz, B. (Benno), Royle, N.A. (Natalie), Shen, L. (Li), Sprooten, R. (Roy), Trabzuni, D. (Danyah), Van Der Marel, S.S.L. (Saskia S. L.), Van Hulzen, K.J.E. (Kimm J. E.), Walton, E. (Esther), Björnsson, A. (Asgeir), Almasy, L. (Laura), Ames, D.J. (David), Arepalli, S. (Sampath), Assareh, A.A., Bastin, M.E. (Mark), Brodaty, H. (Henry), Bulayeva, K. (Kazima), Carless, M.A. (Melanie), Cichon, S. (Sven), Corvin, A. (Aiden), Curran, J.E. (Joanne), Czisch, M. (Michael), Zubicaray, G.I. (Greig) de, Dillman, A. (Allissa), Duggirala, A. (Aparna), Dyer, M.D. (Matthew), Erk, S., Fedko, I. (Iryna), Ferrucci, L. (Luigi), Foroud, T. (Tatiana), Fox, P.T. (Peter), Fukunaga, M. (Masaki), Raphael Gibbs, J., Göring, H.H.H. (Harald H.), Green, R.C. (Robert C.), Guelfi, S. (Sebastian), Hansell, N.K. (Narelle), Hartman, C.A. (Catharina), Hegenscheid, K. (Katrin), Heinz, J. (Judith), Hernandez, D.G. (Dena), Heslenfeld, D.J. (Dirk), Hoekstra, P.J. (Pieter), Holsboer, F., Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Ikeda, M. (Masashi), Jack Jr., C.R. (Clifford), Jenkinson, S. (Sarah), Johnson, R. (Robert), Kanai, R. (Ryota), Keil, M. (Maria), Kent, J.W. (Jack W.), Kochunov, P. (Peter), Kwok, J.B. (John B.), Lawrie, S. (Stephen), Liu, X. (Xinmin), Longo, D.L. (Dan L.), Mcmahon, K.L. (Katie), Meisenzahl, E. (Eva), Melle, I. (Ingrid), Mohnke, S. (Sebastian), Montgomery, G.W. (Grant), Mostert, J.C. (Jeanette C.), Mühleisen, T.W. (Thomas), Nalls, M.A. (Michael), Nichols, T.E. (Thomas), Nilsson, L.G., Nöthen, M.M. (Markus), Ohi, K. (Kazutaka), Olvera, R.L. (Rene), Perez-Iglesias, R. (Rocio), Pike, G.B. (Bruce), Potkin, S.G. (Steven), Reinvang, I. (Ivar), Reppermund, S., Rietschel, M. (Marcella), Seiferth, N. (Nina), Rosen, G.D. (Glenn D.), Rujescu, D. (Dan), Schnell, K. (Kerry), Schofield, C.J. (Christopher), Smith, C. (Colin), Steen, V.M. (Vidar), Sussmann, J. (Jessika), Thalamuthu, A. (Anbupalam), Toga, A.W. (Arthur W.), Traynor, B. (Bryan), Troncoso, J.C. (Juan), Turner, J. (Jessica), Valdés Hernández, M.C. (Maria), Ent, D. (Dennis) van 't, Brug, M.P. (Marcel) van der, Wee, N.J. (Nic) van der, Tol, M.J.D. (Marie-José) van, Veltman, D.J. (Dick), Wassink, A.M.J. (Annemarie), Westman, E. (Eric), Zielke, R.H. (Ronald H.), Zonderman, A.B. (Alan B.), Ashbrook, D.G. (David G.), Hager, R. (Reinmar), Lu, L. (Lu), Mcmahon, F.J. (Francis J), Morris, D.W. (Derek W), Williams, R.W. (Robert W.), Brunner, H.G., Buckner, M., Buitelaar, J.K. (Jan K.), Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cavalleri, G. (Gianpiero), Crespo-Facorro, B. (Benedicto), Dale, A.M. (Anders), Davies, G.E. (Gareth), Delanty, N., Depondt, C. (Chantal), Djurovic, S. (Srdjan), Drevets, D.A. (Douglas), Espeseth, T. (Thomas), Gollub, R.L. (Randy), Ho, B.C. (Beng ), Hoffmann, W. (Wolfgang), Hosten, N. (Norbert), Kahn, R. (René), Le Hellard, S. (Stephanie), Meyer-Lindenberg, A., Müller-Myhsok, B. (B.), Nauck, M. (Matthias), Nyberg, L. (Lars), Pandolfo, M. (Massimo), Penninx, B.W.J.H. (Brenda), Roffman, J.L. (Joshua), Sisodiya, S.M. (Sanjay), Smoller, J.W., Bokhoven, H. (Hans) van, Haren, N.E.M. (Neeltje E.) van, Völzke, H. (Henry), Walter, H.J. (Henrik), Weiner, M.W. (Michael), Wen, W. (Wei), White, T.J.H. (Tonya), Agartz, I. (Ingrid), Andreassen, O.A. (Ole), Blangero, J. (John), Boomsma, D.I. (Dorret), Brouwer, R.M. (Rachel), Cannon, D.M. (Dara), Cookson, M.R. (Mark), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Donohoe, D.J. (Dennis), Fernandez, G. (Guillén), Fisher, S.E. (Simon), Francks, C. (Clyde), Glahn, D.C. (David), Grabe, H.J. (Hans Jörgen), Gruber, O. (Oliver), Hardy, J. (John), Hashimoto, R. (Ryota), Hulshoff Pol, H.E. (Hilleke), Jönsson, E.G. (Erik), Kloszewska, I. (Iwona), Lovestone, S. (Simon), Mattay, V.S. (Venkata S.), Mecocci, P. (Patrizia), McDonald, C. (Colm), McIntosh, A.M. (Andrew), Ophoff, R.A. (Roel), Paus, T. (Tomas), Pausova, Z. (Zdenka), Ryten, M. (Mina), Sachdev, P.S. (Perminder), Saykin, A.J. (Andrew), Simmons, A. (Andrew), Singleton, A. (Andrew), Soininen, H. (H.), Wardlaw, J.M. (J.), Weale, M.E. (Michael), Weinberger, D.R. (Daniel), Adams, H.H.H. (Hieab), Launer, L.J. (Lenore), Seiler, S. (Stephan), Schmidt, R. (Reinhold), Chauhan, G. (Ganesh), Satizabal, C.L. (Claudia), Becker, J.T. (James), Yanek, L.R. (Lisa), Lee, S.J. (Sven) van der, Ebling, M. (Maritza), Fischl, B. (Bruce), Longstreth Jr, W.T., Greve, D. (Douglas), Nyquist, P. (Paul), Vinke, L.N. (Louis N.), Duijn, C.M. (Cornelia) van, Xue, L. (Luting), Mazoyer, B. (Bernard), Bis, J.C. (Joshua), Gudnason, V. (Vilmundur), Seshadri, S. (Sudha), Ikram, M.A. (Arfan), Martin, N.G. (Nicholas), Wright, M.J. (Margaret), Schumann, G. (Gunter), Franke, B. (Barbara), Thompson, P.M. (Paul), and Medland, S.E. (Sarah)
- Abstract
The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, a
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- 2015
- Full Text
- View/download PDF
59. Association of Alzheimer's disease GWAS loci with MRI markers of brain aging
- Author
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Chauhan, G. (Ganesh), Adams, H.H.H. (Hieab), Bis, J.C. (Joshua), Weinstein, G. (Galit), Yu, L. (Lei), Töglhofer, A.M. (Anna Maria), Smith, A.V. (Davey), Lee, S.J. (Sven) van der, Gottesman, R.F. (Rebecca), Thomson, R. (Russell), Wang, J. (Jing), Yang, Q. (Qiong Fang), Niessen, W.J. (Wiro), Lopez, O.L. (Oscar), Becker, J.T. (James), Phan, T.G. (Thanh), Beare, R.J. (Richard), Arfanakis, K. (Konstantinos), Fleischman, D. (Debra), Vernooij, M.W. (Meike), Mazoyer, B. (Bernard), Schmidt, R. (Reinhold), Srikanth, V. (Velandai), Knopman, D.S. (David), Jack Jr., C.R. (Clifford), Amouyel, P. (Philippe), Hofman, A. (Albert), DeCarli, C. (Charles), Tzourio, C. (Christophe), Duijn, C.M. (Cornelia) van, Bennett, D.A. (David), Longstreth Jr, W.T., Mosley, T.H. (Thomas H.), Fornage, M. (Myriam), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Ikram, M.A. (Arfan), Debette, S. (Stéphanie), Chauhan, G. (Ganesh), Adams, H.H.H. (Hieab), Bis, J.C. (Joshua), Weinstein, G. (Galit), Yu, L. (Lei), Töglhofer, A.M. (Anna Maria), Smith, A.V. (Davey), Lee, S.J. (Sven) van der, Gottesman, R.F. (Rebecca), Thomson, R. (Russell), Wang, J. (Jing), Yang, Q. (Qiong Fang), Niessen, W.J. (Wiro), Lopez, O.L. (Oscar), Becker, J.T. (James), Phan, T.G. (Thanh), Beare, R.J. (Richard), Arfanakis, K. (Konstantinos), Fleischman, D. (Debra), Vernooij, M.W. (Meike), Mazoyer, B. (Bernard), Schmidt, R. (Reinhold), Srikanth, V. (Velandai), Knopman, D.S. (David), Jack Jr., C.R. (Clifford), Amouyel, P. (Philippe), Hofman, A. (Albert), DeCarli, C. (Charles), Tzourio, C. (Christophe), Duijn, C.M. (Cornelia) van, Bennett, D.A. (David), Longstreth Jr, W.T., Mosley, T.H. (Thomas H.), Fornage, M. (Myriam), Launer, L.J. (Lenore), Seshadri, S. (Sudha), Ikram, M.A. (Arfan), and Debette, S. (Stéphanie)
- Abstract
Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N= 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (. p= 0.0054) and CD33 (rs3865444) with smaller intracranial volume (. p= 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (. p= 0.0006) and BIN1 with HV (. p= 0.00089). Aweighted AD genetic risk score was associated with smaller HV (beta ± SE=-0.047 ± 0.013, p= 0.00041), even after excluding the APOE locus (. p= 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.
- Published
- 2015
- Full Text
- View/download PDF
60. A priori collaboration in population imaging: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement consortium
- Author
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Adams, H.H.H. (Hieab), Hilal, S. (Saima), Schwingenschuh, P. (Petra), Wittfeld, K. (Katharina), Lee, S.J. (Sven) van der, DeCarli, C. (Charles), Vernooij, M.W. (Meike), Katschnig-Winter, P. (Petra), Habes, M. (Mohamad), Chen, C. (Christopher), Seshadri, S. (Sudha), Duijn, C.M. (Cornelia) van, Ikram, M.K. (Kamran), Grabe, H.J. (Hans Jörgen), Schmidt, R. (Reinhold), Ikram, M.A. (Arfan), Adams, H.H.H. (Hieab), Hilal, S. (Saima), Schwingenschuh, P. (Petra), Wittfeld, K. (Katharina), Lee, S.J. (Sven) van der, DeCarli, C. (Charles), Vernooij, M.W. (Meike), Katschnig-Winter, P. (Petra), Habes, M. (Mohamad), Chen, C. (Christopher), Seshadri, S. (Sudha), Duijn, C.M. (Cornelia) van, Ikram, M.K. (Kamran), Grabe, H.J. (Hans Jörgen), Schmidt, R. (Reinhold), and Ikram, M.A. (Arfan)
- Abstract
Introduction: Virchow-Robin spaces (VRS), or perivascular spaces, are compartments of interstitial fluid enclosing cerebral blood vessels and are potential imaging markers of various underlying brain pathologies. Despite a growing interest in the study of enlarged VRS, the heterogeneity in rating and quantification methods combined with small sample sizes have so far hampered advancement in the field. Methods: The Uniform Neuro-Imaging of Virchow-Robin Spaces Enlargement (UNIVRSE) consortium was established with primary aims to harmonize rating and analysis (www.uconsortium.org). The UNIVRSE consortium brings together 13 (sub)cohorts from five countries, totaling 16,000 subjects and over 25,000 scans. Eight different magnetic resonance imaging protocols were used in the consortium. Results: VRS rating was harmonized using a validated protocol that was developed by the two founding members, with high reliability independent of scanner type, rater experience, or concomitant brain pathology. Initial analyses revealed risk factors for enlarged VRS including increased age, sex, high blood pressure, brain infarcts, and white matter lesions, but this varied by brain region. Discussion: Early collaborative efforts between cohort studies with respect to data harmonization and joint analyses can advance the field of population (neuro)imaging. The UNIVRSE consortium will focus efforts on other potential correlates of enlarged VRS, including genetics, cognition, stroke, and dementia.
- Published
- 2015
- Full Text
- View/download PDF
61. Common genetic variants influence human subcortical brain structures
- Author
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Hibar, D.P., Stein, J.L., Renteria, M.E., Arias-Vasquez, A., Desrivières, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J., Brown, A.A., Mallar Chakravarty, M., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., den Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santiañez, R., Rose, E.J., Salami, A., Sämann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., van Donkelaar, M.M.J., van Eijk, K.R., Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M.H., Hartberg, C.B., Haukvik, U.K., Heister, A.J.G.A.M., Hoehn, D., Kasperaviciute, D., Liewald, D.C.M., Lopez, L.M., Makkinje, R.R.R., Matarin, M., Naber, M.A.M., Reese McKay, D., Needham, M., Nugent, A.C., Pütz, B., Royle, N.A., Shen, Li, Sprooten, E., Trabzuni, D., van der Marel, S.S.L., van Hulzen, K.J.E., Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., de Zubicaray, G.I., Dillman, A., Duggirala, R., Dyer, T.D., Erk, S., Fedko, I.O., Ferrucci, L., Foroud, T.M., Fox, P.T., Fukunaga, M., Raphael Gibbs, J., Göring, H.H.H., Green, R.C., Guelfi, S., Hansell, N.K., Hartman, C.A., Hegenscheid, K., Heinz, A., Hernandez, D.G., Heslenfeld, D.J., Hoekstra, P.J., Holsboer, F., Homuth, G., Hottenga, J-J, Ikeda, M., Jack, C.R., Jenkinson, M., Johnson, R., Kanai, R., Keil, M., Kent, J.W., Kochunov, P., Kwok, J.B., Lawrie, S.M., Liu, X., Longo, D.L., McMahon, K.L., Meisenzahl, E., Melle, I., Mohnke, S., Montgomery, G.W., Mostert, J.C., Mühleisen, T.W., Nalls, M.A., Nichols, T.E., Nilsson, L.G., Nöthen, M.M., Ohi, K., Olvera, R.L., Perez-Iglesias, R., Bruce Pike, G., Potkin, S.G., Reinvang, I., Reppermund, S., Rietschel, M., Romanczuk-Seiferth, N., Rosen, G.D., Rujescu, D., Schnell, K., Schofield, P.R., Smith, C., Steen, V.M., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Valdés Hernández, M.C., van 't Ent, D., van der Brug, M., van der Wee, N.J.A., van Tol, M-J, Veltman, D.J., Wassink, T.H., Westman, E., Zielke, R.H., Zonderman, A.B., Ashbrook, D.G., Hager, R., Lu, L., McMahon, F.J., Morris, D.W., Williams, R.W., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Cahn, W., Calhoun, V.D., Cavalleri, G.L., Crespo-Facorro, B., Dale, A.M., Davies, G.E., Delanty, N., Depondt, C., Djurovic, S., Drevets, W.C., Espeseth, T., Gollub, R.L., Ho, B-C., Hoffmann, W., Hosten, N., Kahn, R.S., Le Hellard, S., Meyer-Lindenberg, A., Müller-Myhsok, B., Nauck, M., Nyberg, L., Pandolfo, M., Penninx, B.W.J.H., Roffman, J.L., Sisodiya, S.M., Smoller, J.W., van Bokhoven, H., van Haren, N.E.M., Völzke, H., Walter, H., Weiner, M.W., Wen, W., White, T., Agartz, I., Andreassen, O.A., Blangero, J., Boomsma, D.I., Brouwer, R.M., Cannon, D.M., Cookson, M.R., de Geus, E.J.C., Deary, I.J., Donohoe, G., Fernández, G., Fisher, S.E., Francks, C., Glahn, D.C., Grabe, H.J., Gruber, O., Hardy, J., Hashimoto, R., Hulshoff Pol, H.E., Jönsson, E.G., Kloszewska, I., Lovestone, S., Mattay, V.S., Mecocci, P., McDonald, C., McIntosh, A.M., Ophoff, R.A., Paus, T., Pausova, Z., Ryten, M., Sachdev, P.S., Saykin, A.J., Simmons, A., Singleton, A., Soininen, H., Wardlaw, J.M., Weale, M.E., Weinberger, D.R., Adams, H.H.H., Launer, L.J., Seiler, S., Schmidt, R., Chauhan, G., Satizabal, C.L., Becker, J.T., Yanek, L., van der Lee, S.J., Ebling, M., Fischl, B., Longstreth, W.T., Greve, D., Schmidt, H., Nyquist, P., Vinke, L.N., van Duijn, C.M., Xue, L., Mazoyer, B., Bis, J.C., Gudnason, V., Seshadri, S., Ikram, M.A., Martin, N.G., Wright, M.J., Schumann, G., Franke, B., Thompson, P.M., Medland, S.E., Hibar, D.P., Stein, J.L., Renteria, M.E., Arias-Vasquez, A., Desrivières, S., Jahanshad, N., Toro, R., Wittfeld, K., Abramovic, L., Andersson, M., Aribisala, B.S., Armstrong, N.J., Bernard, M., Bohlken, M.M., Boks, M.P., Bralten, J., Brown, A.A., Mallar Chakravarty, M., Chen, Q., Ching, C.R.K., Cuellar-Partida, G., den Braber, A., Giddaluru, S., Goldman, A.L., Grimm, O., Guadalupe, T., Hass, J., Woldehawariat, G., Holmes, A.J., Hoogman, M., Janowitz, D., Jia, T., Kim, S., Klein, M., Kraemer, B., Lee, P.H., Olde Loohuis, L.M., Luciano, M., Macare, C., Mather, K.A., Mattheisen, M., Milaneschi, Y., Nho, K., Papmeyer, M., Ramasamy, A., Risacher, S.L., Roiz-Santiañez, R., Rose, E.J., Salami, A., Sämann, P.G., Schmaal, L., Schork, A.J., Shin, J., Strike, L.T., Teumer, A., van Donkelaar, M.M.J., van Eijk, K.R., Walters, R.K., Westlye, L.T., Whelan, C.D., Winkler, A.M., Zwiers, M.P., Alhusaini, S., Athanasiu, L., Ehrlich, S., Hakobjan, M.M.H., Hartberg, C.B., Haukvik, U.K., Heister, A.J.G.A.M., Hoehn, D., Kasperaviciute, D., Liewald, D.C.M., Lopez, L.M., Makkinje, R.R.R., Matarin, M., Naber, M.A.M., Reese McKay, D., Needham, M., Nugent, A.C., Pütz, B., Royle, N.A., Shen, Li, Sprooten, E., Trabzuni, D., van der Marel, S.S.L., van Hulzen, K.J.E., Walton, E., Wolf, C., Almasy, L., Ames, D., Arepalli, S., Assareh, A.A., Bastin, M.E., Brodaty, H., Bulayeva, K.B., Carless, M.A., Cichon, S., Corvin, A., Curran, J.E., Czisch, M., de Zubicaray, G.I., Dillman, A., Duggirala, R., Dyer, T.D., Erk, S., Fedko, I.O., Ferrucci, L., Foroud, T.M., Fox, P.T., Fukunaga, M., Raphael Gibbs, J., Göring, H.H.H., Green, R.C., Guelfi, S., Hansell, N.K., Hartman, C.A., Hegenscheid, K., Heinz, A., Hernandez, D.G., Heslenfeld, D.J., Hoekstra, P.J., Holsboer, F., Homuth, G., Hottenga, J-J, Ikeda, M., Jack, C.R., Jenkinson, M., Johnson, R., Kanai, R., Keil, M., Kent, J.W., Kochunov, P., Kwok, J.B., Lawrie, S.M., Liu, X., Longo, D.L., McMahon, K.L., Meisenzahl, E., Melle, I., Mohnke, S., Montgomery, G.W., Mostert, J.C., Mühleisen, T.W., Nalls, M.A., Nichols, T.E., Nilsson, L.G., Nöthen, M.M., Ohi, K., Olvera, R.L., Perez-Iglesias, R., Bruce Pike, G., Potkin, S.G., Reinvang, I., Reppermund, S., Rietschel, M., Romanczuk-Seiferth, N., Rosen, G.D., Rujescu, D., Schnell, K., Schofield, P.R., Smith, C., Steen, V.M., Sussmann, J.E., Thalamuthu, A., Toga, A.W., Traynor, B.J., Troncoso, J., Turner, J.A., Valdés Hernández, M.C., van 't Ent, D., van der Brug, M., van der Wee, N.J.A., van Tol, M-J, Veltman, D.J., Wassink, T.H., Westman, E., Zielke, R.H., Zonderman, A.B., Ashbrook, D.G., Hager, R., Lu, L., McMahon, F.J., Morris, D.W., Williams, R.W., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Cahn, W., Calhoun, V.D., Cavalleri, G.L., Crespo-Facorro, B., Dale, A.M., Davies, G.E., Delanty, N., Depondt, C., Djurovic, S., Drevets, W.C., Espeseth, T., Gollub, R.L., Ho, B-C., Hoffmann, W., Hosten, N., Kahn, R.S., Le Hellard, S., Meyer-Lindenberg, A., Müller-Myhsok, B., Nauck, M., Nyberg, L., Pandolfo, M., Penninx, B.W.J.H., Roffman, J.L., Sisodiya, S.M., Smoller, J.W., van Bokhoven, H., van Haren, N.E.M., Völzke, H., Walter, H., Weiner, M.W., Wen, W., White, T., Agartz, I., Andreassen, O.A., Blangero, J., Boomsma, D.I., Brouwer, R.M., Cannon, D.M., Cookson, M.R., de Geus, E.J.C., Deary, I.J., Donohoe, G., Fernández, G., Fisher, S.E., Francks, C., Glahn, D.C., Grabe, H.J., Gruber, O., Hardy, J., Hashimoto, R., Hulshoff Pol, H.E., Jönsson, E.G., Kloszewska, I., Lovestone, S., Mattay, V.S., Mecocci, P., McDonald, C., McIntosh, A.M., Ophoff, R.A., Paus, T., Pausova, Z., Ryten, M., Sachdev, P.S., Saykin, A.J., Simmons, A., Singleton, A., Soininen, H., Wardlaw, J.M., Weale, M.E., Weinberger, D.R., Adams, H.H.H., Launer, L.J., Seiler, S., Schmidt, R., Chauhan, G., Satizabal, C.L., Becker, J.T., Yanek, L., van der Lee, S.J., Ebling, M., Fischl, B., Longstreth, W.T., Greve, D., Schmidt, H., Nyquist, P., Vinke, L.N., van Duijn, C.M., Xue, L., Mazoyer, B., Bis, J.C., Gudnason, V., Seshadri, S., Ikram, M.A., Martin, N.G., Wright, M.J., Schumann, G., Franke, B., Thompson, P.M., and Medland, S.E.
- Abstract
The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
- Published
- 2015
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