Author: "Sachdev P.S." - Searchworks@Jio Institute Digital Library Search Results

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236 results on '"Sachdev P.S."'

1. A systematic review of diet, nutrition, and medication use among centenarians and near centenarians worldwide

Author: Dai, Z., primary, Lee, S.Y., additional, Sharma, S., additional, Tan, E.C.K., additional, Ullah, S., additional, Bodady, H., additional, and Sachdev, P.S., additional
Published: 2024
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2. The global burden of cerebral small vessel disease in low- and middle-income countries: A systematic review and meta-analysis.

Author: Lam, B.Y.K., Cai, Y., Akinyemi, R., Biessels, G.J., Brink, H. van den, Chen, C, Cheung, C.W., Chow, K.N., Chung, H.K.H., Duering, M., Fu, S.T., Gustafson, D., Hilal, S., Hui, V.M.H., Kalaria, R., Kim, S., Lam, M.L.M., Leeuw, F.E. de, Li, A.S.M., Markus, H.S., Marseglia, A., Zheng, H., O'Brien, J., Pantoni, L., Sachdev, P.S., Smith, E.E., Wardlaw, J., Mok, V.C.T., Lam, B.Y.K., Cai, Y., Akinyemi, R., Biessels, G.J., Brink, H. van den, Chen, C, Cheung, C.W., Chow, K.N., Chung, H.K.H., Duering, M., Fu, S.T., Gustafson, D., Hilal, S., Hui, V.M.H., Kalaria, R., Kim, S., Lam, M.L.M., Leeuw, F.E. de, Li, A.S.M., Markus, H.S., Marseglia, A., Zheng, H., O'Brien, J., Pantoni, L., Sachdev, P.S., Smith, E.E., Wardlaw, J., and Mok, V.C.T.
Abstract: 01 januari 2023, Item does not contain fulltext, BACKGROUND: Cerebral small vessel disease (cSVD) is a major cause of stroke and dementia. Previous studies on the prevalence of cSVD are mostly based on single geographically defined cohorts in high-income countries. Studies investigating the prevalence of cSVD in low- and middle-income countries (LMICs) are expanding but have not been systematically assessed. AIM: This study aims to systematically review the prevalence of cSVD in LMICs. RESULTS: Articles were searched from the Ovid MEDLINE and EMBASE databases from 1 January 2000 to 31 March 2022, without language restrictions. Title/abstract screening, full-text review, and data extraction were performed by two to seven independent reviewers. The prevalence of cSVD and study sample size were extracted by pre-defined world regions and health status. The Risk of Bias for Non-randomized Studies tool was used. The protocol was registered on PROSPERO (CRD42022311133). A meta-analysis of proportion was performed to assess the prevalence of different magnetic resonance imaging markers of cSVD, and a meta-regression was performed to investigate associations between cSVD prevalence and type of study, age, and male: female ratio. Of 2743 studies identified, 42 studies spanning 12 global regions were included in the systematic review. Most of the identified studies were from China (n = 23). The median prevalence of moderate-to-severe white matter hyperintensities (WMHs) was 20.5%, 40.5%, and 58.4% in the community, stroke, and dementia groups, respectively. The median prevalence of lacunes was 0.8% and 33.5% in the community and stroke groups. The median prevalence of cerebral microbleeds (CMBs) was 10.7% and 22.4% in the community and stroke groups. The median prevalence of moderate-to-severe perivascular spaces was 25.0% in the community. Meta-regression analyses showed that the weighted median age (51.4 ± 0.0 years old; range: 36.3-80.2) was a significant predictor of the prevalence of moderate-to-severe WMH and lacunes
Published: 2023

3. Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.

Author: Mahalingam, G., Samtani, S., Lam, B.C.P., Lipnicki, D.M., Lima-Costa, M.F., Blay, S.L., Castro-Costa, E., Shifu, X., Guerchet, M., Preux, P.M., Gbessemehlan, A., Skoog, I., Najar, J., Sterner, T.R., Scarmeas, N., Yannakoulia, M., Dardiotis, T., Kim, K.W., Riedel-Heller, S., Röhr, S., Pabst, A., Shahar, S., Numbers, K., Ganguli, M., Hughes, T.F., Chang, Chun Chin, Crowe, M., Ng, T.P., Gwee, X., Chua, D.Q.L., Rymaszewska, J., Wolf-Ostermann, K., Welmer, A.K., Stafford, J., Melis, R.J.F., Vernooij-Dassen, M.J.F.J., Jeon, Y.H., Sachdev, P.S., Brodaty, H., Mahalingam, G., Samtani, S., Lam, B.C.P., Lipnicki, D.M., Lima-Costa, M.F., Blay, S.L., Castro-Costa, E., Shifu, X., Guerchet, M., Preux, P.M., Gbessemehlan, A., Skoog, I., Najar, J., Sterner, T.R., Scarmeas, N., Yannakoulia, M., Dardiotis, T., Kim, K.W., Riedel-Heller, S., Röhr, S., Pabst, A., Shahar, S., Numbers, K., Ganguli, M., Hughes, T.F., Chang, Chun Chin, Crowe, M., Ng, T.P., Gwee, X., Chua, D.Q.L., Rymaszewska, J., Wolf-Ostermann, K., Welmer, A.K., Stafford, J., Melis, R.J.F., Vernooij-Dassen, M.J.F.J., Jeon, Y.H., Sachdev, P.S., and Brodaty, H.
Abstract: Item does not contain fulltext, INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, M(age) = 70.67 (40-102), 58.86% female, M(education) = 8.43 years, M(follow-up) = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and havin, 01 november 2023
Published: 2023

4. Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Author: Hop, P.J., Zwamborn, R.A.J., Hannon, E., Shireby, G.L., Nabais, M.F., Walker, E.M., van Rheenen, W., van Vugt, J.J.F.A., Dekker, A.M., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Moisse, M., Baird, D., Al Khleifat, A., Iacoangeli, A., Ticozzi, N., Ratti, A., Cooper-Knock, J., Morrison, K.E., Shaw, P.J., Basak, A.N., Chiò, A., Calvo, A., Moglia, C., Canosa, A., Brunetti, M., Grassano, M., Gotkine, M., Lerner, Y., Zabari, M., Vourc’h, P., Corcia, P., Couratier, P., Mora Pardina, J.S., Salas, T., Dion, P., Ross, J.P., Henderson, R.D., Mathers, S., McCombe, P.A., Needham, M., Nicholson, G., Rowe, D.B., Pamphlett, R., Mather, K.A., Sachdev, P.S., Furlong, S., Garton, F.C., Henders, A.K., Lin, T., Ngo, S.T., Steyn, F.J., Wallace, L., Williams, K.L., Neto, M.M., Cauchi, R.J., Blair, I.P., Kiernan, M.C., Drory, V., Povedano, M., de Carvalho, M., Pinto, S., Weber, M., Rouleau, G.A., Silani, V., Landers, J.E., Shaw, C.E., Andersen, P.M., McRae, A.F., van Es, M.A., Pasterkamp, R.J., Wray, N.R., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Tsai, E., Runz, H., Al-Chalabi, A., van den Berg, L.H., Van Damme, P., Mill, J., Veldink, J.H., Heijmans, B.T., t Hoen, P.A.C., van Meurs, J., Jansen, R., Franke, L., Boomsma, D.I., Pool, R., van Dongen, J., Hottenga, J.J., van Greevenbroek, M.M.J., Stehouwer, C.D.A., van der Kallen, C.J.H., Schalkwijk, C.G., Wijmenga, C., Zhernakova, S., Tigchelaar, E.F., Slagboom, P.E., Beekman, M., Deelen, J., Van Heemst, D., van Duijn, C.M., Hofman, B.A., Isaacs, A., Uitterlinden, A.G., van Meurs, J.B.C., Jhamai, P.M., Verbiest, M., Suchiman, H.E.D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Mei, H., van Iterson, M., van Galen, M., Bot, J., Zhernakova, D.V., van ‘t Hof, P., Deelen, P., Nooren, I., Moed, M., Vermaat, M., Luijk, R., Jan Bonder, M., van Dijk, F., Arindrarto, W., Kielbasa, S.M., Swertz, M.A., van Zwet, E.W., Hoen, P.A.C., Bensimon, G., Chio, A., Smith, G.D., Hop, P.J., Zwamborn, R.A.J., Hannon, E., Shireby, G.L., Nabais, M.F., Walker, E.M., van Rheenen, W., van Vugt, J.J.F.A., Dekker, A.M., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Moisse, M., Baird, D., Al Khleifat, A., Iacoangeli, A., Ticozzi, N., Ratti, A., Cooper-Knock, J., Morrison, K.E., Shaw, P.J., Basak, A.N., Chiò, A., Calvo, A., Moglia, C., Canosa, A., Brunetti, M., Grassano, M., Gotkine, M., Lerner, Y., Zabari, M., Vourc’h, P., Corcia, P., Couratier, P., Mora Pardina, J.S., Salas, T., Dion, P., Ross, J.P., Henderson, R.D., Mathers, S., McCombe, P.A., Needham, M., Nicholson, G., Rowe, D.B., Pamphlett, R., Mather, K.A., Sachdev, P.S., Furlong, S., Garton, F.C., Henders, A.K., Lin, T., Ngo, S.T., Steyn, F.J., Wallace, L., Williams, K.L., Neto, M.M., Cauchi, R.J., Blair, I.P., Kiernan, M.C., Drory, V., Povedano, M., de Carvalho, M., Pinto, S., Weber, M., Rouleau, G.A., Silani, V., Landers, J.E., Shaw, C.E., Andersen, P.M., McRae, A.F., van Es, M.A., Pasterkamp, R.J., Wray, N.R., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Tsai, E., Runz, H., Al-Chalabi, A., van den Berg, L.H., Van Damme, P., Mill, J., Veldink, J.H., Heijmans, B.T., t Hoen, P.A.C., van Meurs, J., Jansen, R., Franke, L., Boomsma, D.I., Pool, R., van Dongen, J., Hottenga, J.J., van Greevenbroek, M.M.J., Stehouwer, C.D.A., van der Kallen, C.J.H., Schalkwijk, C.G., Wijmenga, C., Zhernakova, S., Tigchelaar, E.F., Slagboom, P.E., Beekman, M., Deelen, J., Van Heemst, D., van Duijn, C.M., Hofman, B.A., Isaacs, A., Uitterlinden, A.G., van Meurs, J.B.C., Jhamai, P.M., Verbiest, M., Suchiman, H.E.D., Verkerk, M., van der Breggen, R., van Rooij, J., Lakenberg, N., Mei, H., van Iterson, M., van Galen, M., Bot, J., Zhernakova, D.V., van ‘t Hof, P., Deelen, P., Nooren, I., Moed, M., Vermaat, M., Luijk, R., Jan Bonder, M., van Dijk, F., Arindrarto, W., Kielbasa, S.M., Swertz, M.A., van Zwet, E.W., Hoen, P.A.C., Bensimon, G., Chio, A., and Smith, G.D.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation–based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
Published: 2022

5. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chiò, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., Di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.
Abstract: Correction to: Nature Genetics https://doi.org/10.1038/s41588-021-00973-1, published online 6 December 2021. In the version of this article initially published, the affiliation for Nazli Başak appeared incorrectly. Nazli Başak is at Koç University, School of Medicine, KUTTAM-NDAL, Istanbul, Turkey, and not Bogazici University. The error has been corrected in the HTML and PDF versions of the article.
Published: 2022

6. Associations between social connections and cognition: a global collaborative individual participant data meta-analysis

Author: Samtani, S., Mahalingam, G., Lam, B.C.P., Lipnicki, D.M., Lima-Costa, M.F., Blay, S.L., Castro-Costa, E., Shifu, X., Guerchet, M., Preux, P.M., Gbessemehlan, A., Skoog, I., Najar, J., Sterner, T. Rydberg, Scarmeas, N., Kim, K.W., Riedel-Heller, S., Röhr, S., Pabst, A., Shahar, S., Numbers, K., Ganguli, M., Jacobsen, E., Hughes, T.F., Crowe, M., Ng, T.P., Maddock, J., Marseglia, A., Melis, R.J.F., Szcześniak, D., Wiegelmann, H., Vernooij-Dassen, M.J.F.J., Jeon, Y.H., Sachdev, P.S., Brodaty, H., Samtani, S., Mahalingam, G., Lam, B.C.P., Lipnicki, D.M., Lima-Costa, M.F., Blay, S.L., Castro-Costa, E., Shifu, X., Guerchet, M., Preux, P.M., Gbessemehlan, A., Skoog, I., Najar, J., Sterner, T. Rydberg, Scarmeas, N., Kim, K.W., Riedel-Heller, S., Röhr, S., Pabst, A., Shahar, S., Numbers, K., Ganguli, M., Jacobsen, E., Hughes, T.F., Crowe, M., Ng, T.P., Maddock, J., Marseglia, A., Melis, R.J.F., Szcześniak, D., Wiegelmann, H., Vernooij-Dassen, M.J.F.J., Jeon, Y.H., Sachdev, P.S., and Brodaty, H.
Abstract: Item does not contain fulltext, BACKGROUND: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. METHODS: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. FINDINGS: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cogn
Published: 2022

7. Recognition of social health: A conceptual framework in the context of dementia research

Author: Vernooij-Dassen, M.J.F.J., Verspoor, E., Samtani, S., Sachdev, P.S., Arfan Ikram, M., Vernooij, Meike W., Melis, R.J.F., Perry, M., Wolf-Ostermann, K., Vernooij-Dassen, M.J.F.J., Verspoor, E., Samtani, S., Sachdev, P.S., Arfan Ikram, M., Vernooij, Meike W., Melis, R.J.F., Perry, M., and Wolf-Ostermann, K.
Abstract: Contains fulltext : 288208.pdf (Publisher’s version ) (Open Access)
Published: 2022

8. Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning

Author: 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.
Published: 2022

9. Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Author: Abbafati, C., Machado, D.B., Cislaghi, B., Salman, O.M., Karanikolos, M., McKee, M., Abbas, K.M., Brady, O.J., Larson, H.J., Trias-Llimós, S., Cummins, S., Langan, S.M., Sartorius, B., Hafiz, A., Jenabi, E., Mohammad Gholi Mezerji, N., Borzouei, S., Azarian, G., Khazaei, S., Abbasi, M., Asghari, B., Masoumi, S., Komaki, H., Taherkhani, A., Adabi, M., Abbasifard, M., Bazmandegan, G., Kamiab, Z., Vakilian, A., Anjomshoa, M., Mokari, A., Sabour, S., Shahbaz, M., Saeedi, R., Ahmadieh, H., Yousefinezhadi, T., Haj-Mirzaian, A., Nikbakhsh, R., Safi, S., Asgari, S., Irvani, S.N., Jahanmehr, N., Ramezanzadeh, K., Abbasi-Kangevari, M., Khayamzadeh, M., Abbastabar, H., Shirkoohi, R., Fazlzadeh, M., Janjani, H., Hosseini, M., Mansournia, M., Tohidinik, H., Bakhtiari, A., Fazaeli, A., Mousavi, S., Hasanzadeh, A., Nabavizadeh, B., Malekzadeh, R., Hashemian, M., Pourshams, A., Salimzadeh, H., Sepanlou, S.G., Afarideh, M., Esteghamati, A., Esteghamati, S., Ghajar, A., Heidari, B., Rezaei, N., Mohamadi, E., Rahimi-Movaghar, A., Rahim, F., Eskandarieh, S., Sahraian, M., Mohebi, F., Aminorroaya, A., Ebrahimi, H., Farzadfar, F., Mohajer, B., Pishgar, F., Saeedi Moghaddam, S., Shabani, M., Zarafshan, H., Abolhassani, H., Hafezi-Nejad, N., Heidari-Soureshjani, R., Abdollahi, M., Farahmand, M., Salamati, P., Mehrabi Nasab, E., Tajdini, M., Aghamir, S., Mirzaei, R., Dibaji Forooshani, Z., Khater, M.M., Abd-Allah, F., Abdelalim, A., Abualhasan, A., El-Jaafary, S.I., Hassan, A., Elsharkawy, A., Khater, A.M., Elhabashy, H.R., Salem, M.R.R., Salem, H., Sadeghi, M., Jafarinia, M., Amini-Rarani, M., Mohammadifard, N., Sarrafzadegan, N., Abdollahpour, I., Sarveazad, A., Tehrani-Banihashemi, A., Yoosefi Lebni, J., Manafi, N., Pazoki Toroudi, H., Dorostkar, F., Alipour, V., Sheikhtaheri, A., Arabloo, J., Azari, S., Ghashghaee, A., Rezapour, A., Naserbakht, M., Kabir, A., Mehri, F., Yousefifard, M., Asadi-Aliabadi, M., Babaee, E., Eshrati, B., Goharinezhad, S., Moradi-Lakeh, M., Abedi, P., Rashedi, V., Kumar, V., Elgendy, I.Y., Basu, S., Park, J., Pereira, A., Norheim, O.F., Eagan, A.W., Cahill, L.E., Sheikh, A., Abushouk, A.I., Kraemer, M.U.G., Thakur, B., Bärnighausen, T.W., Shrime, M.G., Abedi, A., Doshi, C.P., Abegaz, K.H., Geberemariyam, B.S., Aynalem, Y.A., Shiferaw, W.S., Abosetugn, A.E., Aboyans, V., Abrams, E.M., Gitimoghaddam, M., Kissoon, N., Stubbs, J.L., Brauer, M., Iyamu, I.O., Kopec, J.A., Pourmalek, F., Ribeiro, A.P., Malta, D.C., Gomez, R.S., Abreu, L.G., Abrigo, M.R.M., Almulhim, A.M., Dahlawi, S.M.A., Pottoo, F.H., Menezes, R.G., Alanzi, T.M., Alumran, A.K., Abu Haimed, A.K., Madadin, M., Alanezi, F.M., Abu-Gharbieh, E., Saddik, B., Abu-Raddad, L.J., Samy, A.M., El Nahas, N., Shalash, A.S., Nabhan, A.F., Kamath, A.M., Kassebaum, N.J., Aravkin, A.Y., Kochhar, S., Sorensen, R.J.D., Afshin, A., Burkart, K., Cromwell, E.A., Dandona, L., Dharmaratne, S.D., Gakidou, E., Hay, S.I., Kyu, H.H., Lopez, A.D., Lozano, R., Misganaw, A.T., Mokdad, A.H., Naghavi, M., Pigott, D.M., Reiner Jr, R.C., Roth, G.A., Stanaway, J.D., Vollset, S., Vos, T., Wang, H., Lim, S.S., Murray, C.J.L., Kalani, R., Ikuta, K.S., Cho, D.Y., Kneib, C.J., Crowe, C.S., Massenburg, B.B., Morrison, S.D., Acebedo, A., Adelson, J.D., Agesa, K.M., Alam, T., Albertson, S.B., Anderson, J.A., Antony, C.M., Ashbaugh, C., Assmus, M., Azhar, G., Balassyano, S., Bannick, M.S., Barthelemy, C.M., Bender, R.G., Bennitt, F.B., Bertolacci, G.J., Biehl, M.H., Bisignano, C., Boon-Dooley, A.S., Briant, P.S., Bryazka, D., Bumgarner, B.R., Callender, C.S., Cao, J., Castle, C.D., Castro, E., Causey, K., Cercy, K.M., Chalek, J., Charlson, F.J., Cohen, A.J., Comfort, H., Compton, K., Croneberger, A.J., Cruz, J.A., Cunningham, M., Dandona, R., Dangel, W.J., Dean, F.E., DeCleene, N.K., Deen, A., Degenhardt, L., Dingels, Z.V., Dippenaar, I.N., Dirac, M.A., Dolgert, A.J., Emmons-Bell, S., Estep, K., Farag, T., Feigin, V.L., Feldman, R., Ferrara, G., Ferrari, A.J., Fitzgerald, R., Force, L.M., Fox, J.T., Frank, T.D., Fu, W., Fukutaki, K., Fuller, J.E., Fullman, N., Galles, N.C., Gardner, W.M., Gershberg Hayoon, A., Goren, E., Gorman, T.M., Gottlich, H.C., Guo, G., Haddock, B., Hagins, H., Haile, L.M., Hamilton, E.B., Han, C., Han, H., Harvey, J.D., Henny, K., Henrikson, H.J., Henry, N.J., Herbert, M.E., Hsiao, T., Huynh, C.K., Iannucci, V.C., Ippolito, H., Irvine, C.M.S., Jafari, H., Jahagirdar, D., James, S.L., Johnson, C.O., Johnson, S.C., Keller, C., Kemmer, L., Kendrick, P.J., Knight, M., Kocarnik, J.M., Krohn, K.J., Larson, S.L., Lau, K.M., Ledesma, J.R., Leever, A.T., LeGrand, K.E., Lescinsky, H., Lin, C., Liu, H., Liu, Z., Lo, J., Lu, A., Ma, J., Maddison, E.R., Manguerra, H., Marks, A., Martopullo, I., Mastrogiacomo, C.I., May, E.A., Mooney, M.D., Mosser, J.F., Mullany, E.C., Mumford, J., Munro, S.B., Nandakumar, V., Nguyen, J., Nguyen, M., Nichols, E., Nixon, M.R., Odell, C.M., Ong, K.L., Orji, A.U., Ostroff, S.M., Pasovic, M., Paulson, K.R., Pease, S.A., Pennini, A., Pierce, M., Pilz, T.M., Pletcher, M., Rao, P.C., Razo, C., Redford, S.B., Reinig, N., Reitsma, M.B., Rhinehart, P., Robalik, T., Roberts, S., Roberts, N.L.S., Rolfe, S., Sbarra, A.N., Schaeffer, L.E., Shackelford, K.A., Shadid, J., Sharara, F., Shaw, D.H., Sheena, B.S., Simpson, K.E., Smith, A., Spencer, C.N., Spurlock, E.E., Stark, B.A., Steiner, C., Steuben, K.M., Sylte, D.O., Tang, M., Taylor, H.J., Terrason, S., Thomson, A.M., Torre, A.E., Travillian, R., Troeger, C.E., Vongpradith, A., Walters, M.K., Wang, J., Watson, A., Watson, S., Whisnant, J.L., Whiteford, H.A., Wiens, K.E., Wilner, L.B., Wilson, S., Wool, E.E., Wozniak, S.S., Wu, J., Wulf Hanson, S., Wunrow, H., Xu, R., Yadgir, S., Yearwood, J.A., York, H.W., Yuan, C., Zhao, J.T., Zheng, P., Zimsen, S.R.M., Zlavog, B.S., Chang, A.Y., Oren, E., Buchbinder, R., Chin, K.L., Guo, Y., Polkinghorne, K.R., Thrift, A.G., Lee, S.W.H., Ackerman, I.N., Cicuttini, F.M., Li, S., Zaman, S., Suleria, H., Zhang, J., Cowie, B.C., Wijeratne, T., Patton, G.C., Sawyer, S.M., Adair, T., Meretoja, A., Adetokunboh, O.O., Adamu, A.A., Iwu, C.J., Parry, C.D.H., Seedat, S., Ndwandwe, D.E., Mahasha, P.W., Stein, D.J., Nnaji, C.A., Sambala, E.Z., Wiysonge, C.S., Adebayo, O.M., Ilesanmi, O.S., Owolabi, M.O., Adeoye, A.M., Adedeji, I.A., Adekanmbi, V., Ibitoye, S.E., John-Akinola, Y.O., Oluwasanu, M.M., Oghenetega, O.B., Akinyemi, R.O., Zandian, H., Adham, D., Zahirian Moghadam, T., Advani, S.M., Teagle, W.L., Braithwaite, D., Agasthi, P., Saadatagah, S., Afshari, M., Agardh, E.E., Allebeck, P., Danielsson, A., Deuba, K., Carrero, J.J., Mohammad, D.K., Fereshtehnejad, S., Ärnlöv, J., Nowak, C., Cederroth, C.R., Ahmadi, A., Pathak, A., Mills, E.J., Kurmi, O.P., Olagunju, A.T., Agarwal, G., Sathish, T., Aghaali, M., Mohammadbeigi, A., Agrawal, A., Ahmad, T., Ahmadi, K., Maleki, S., Naderi, M., Salahshoor, M.R., Pourmirza Kalhori, R., Almasi, A., Salimi, Y., Siabani, S., Ziapour, A., Barzegar, A., Khazaie, H., Kianipour, N., Amiri, F., Salehi Zahabi, S., Mirzaei, M., Shamsi, M., Najafi, F., Jalali, A., Ghadiri, K., Heydarpour, F., Fattahi, N., Karami Matin, B., Kazemi Karyani, A., Pirsaheb, M., Rajati, F., Sadeghi, E., Safari, Y., Sharafi, K., Soltani, S., Vasseghian, Y., Atafar, Z., Jalilian, F., Mirzaei-Alavijeh, M., Saeidi, S., Soofi, M., Zangeneh, A., Mansouri, B., Ahmadi, M., Khafaie, M.A., Safiri, S., Moghadaszadeh, M., Asghari Jafarabadi, M., Doshmangir, L., Jadidi-Niaragh, F., Ghafourifard, M., Spotin, A., Khodayari, M., Samadi Kafil, H., Kalankesh, L.R., Ahmadpour, E., Yousefi, B., Ansari, F., Hassankhani, H., Karimi, S., Haririan, H., Mereta, S., Ahmed, M.B., Feyissa, G.T., Ciobanu, L.G., Aji, B., Aynalem, G.L., Gebresillassie, B., Tefera, Y.G., Akalu, T.Y., Baraki, A.G., Tesema, G.A., Tessema, Z.T., Tamiru, A.T., Azene, Z.N., Netsere, H.B., Yano, Y., Akinyemiju, T., Wu, C., Zadey, S., Samad, Z., Ji, J.S., Doshi, P.P., John, O., Jha, V., Maulik, P.K., Pesudovs, K., Resnikoff, S., Mitchell, P.B., Sachdev, P.S., Akombi, B., Godinho, M.A., Ivers, R.Q., Peden, A.E., Biswas, R., Boufous, S., Akunna, C.J., Alahdab, F., Hammer, M.S., van Donkelaar, A., Al-Aly, Z., Dellavalle, R.P., Alam, S., Martin, R.V., Alam, N., De Leo, D., Tadakamadla, S.K., Alam, K., Alcalde-Rabanal, J.E., Avila-Burgos, L., Serván-Mori, E., Denova-Gutiérrez, E., Rodríguez-Ramírez, S., Morales, L., Poznańska, A., Wojtyniak, B., Rivera, J.A., Campos-Nonato, I.R., Campuzano Rincon, J., Sánchez-Pimienta, T.G., Mengesha, M.B., Welay, F.T., Alema, N.M., Demsie, D.G., Teame, H., Teklehaimanot, B.F., Alemu, B.W., Gultie, T., Bante, A.B., Yeshitila, Y.G., Geramo, Y.C.D., Glagn, M., Sorrie, M.B., W/hawariat, F.G., Amare, A., Kasa, A., Alemu, Y., Mihretie, K.M., Atnafu, D.D., Demeke, F.M., Melese, A., Bante, S.A., Dessie, G.A., Mengesha, E.W., Nigatu, D., Almadi, M.A.H., Alhabib, K.F., Mohammad, Y., Altirkawi, K.A., Temsah, M., Kugbey, N., Ayanore, M.A., Alhassan, R.K., Ali, M., Ali, S., Alicandro, G., Kalhor, R., Alijanzadeh, M., Alinia, C., Yusefzadeh, H., Didarloo, A., Alizade, H., Nikpoor, A., Aljunid, S.M., Alla, F., Leal, L.F., Almasi-Hashiani, A., Moradzadeh, R., Zamanian, M., Nazari, J., Amini, S., Ghamari, F., Almasri, N.A., Khan, M., Al-Mekhlafi, H.M., Bedi, N., Alonso, J., Ciber, E.S.P., Al-Raddadi, R.M., Zakzuk, J., Alvis-Guzman, N., Alvis-Zakzuk, N.J., Castañeda-Orjuela, C.A., Malagón-Rojas, J.N., Gezae, K., Gesesew, H.A., Muthupandian, S., Gebremeskel, G.G., Berhe, K., Amare, B., Ayza, M.A., Gebremeskel, L.G., Gebreslassie, A.A.A., Bitew, H., Zewdie, K.A., Tela, F.G.G., Gill, T.K., Noubiap, J., Lassi, Z.S., Bhandari, D., Amit, A.L., Antonio, C.T., Faraon, E.A., Lopez, J.F., Atre, S.R., Ballew, S.H., Matsushita, K., Khoja, A.T., Daneshpajouhnejad, P., Ghadimi, M., Shafaat, O., Fanzo, J., Amugsi, D.A., Amul, G.H., Koh, D.S.Q., Venketasubramanian, N., Anbesu, E.W., Mohammed, J.A., Wondmeneh, T.G., Andrei, C., Negoi, R.I., Davitoiu, D.V., Manda, A., Negoi, I., Preotescu, L., Hostiuc, M., Hostiuc, S., Ancuceanu, R., Hasan, M., Leung, J., Anderlini, D., Mamun, A.A., Maravilla, J.C., McGrath, J.J., Lalloo, R., Uddin, R., Erskine, H.E., Knibbs, L.D., Mantilla Herrera, A.M., Santomauro, D.F., Mirica, A., Ausloos, M., Herteliu, C., Oţoiu, A., Pana, A., Andrei, T., Ştefan, S., Androudi, S., Angus, C., Ansari, I., Pourjafar, H., Shams-Beyranvand, M., Ansari-Moghaddam, A., Khammarnia, M., Antonazzo, I., Ferrara, P., Conti, S., Cortesi, P.A., Fornari, C., Lee, P.H., Antriyandarti, E., Yousefi, Z., Rafiei, A., Javidnia, J., Faridnia, R., Anvari, D., Goudarzian, A., Moosazadeh, M., Rezai, M., Daryani, A., Fareed, M., Anwer, R., Appiah, S., Paudel, D., Dichgans, M., Riahi, S., Rajabpour-Sanati, A., Arab-Zozani, M., Arba, A.A.K., Aremu, O., Ariani, F., Aripov, T., Armoon, B., Mahdavi, M.M., Arowosegbe, O.O., Tediosi, F., Aryal, K.K., Mosapour, A., Yaminfirooz, M., Arzani, A., Bijani, A., Jahani, M.A., Mouodi, S., Zamani, M., Asaad, M., Dianatinasab, M., Bahrami, M., Pakshir, K., Asadi-Pooya, 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Mokari, Amin, Mokdad, Ali H, Momen, Natalie C, Monasta, Lorenzo, Mooney, Meghan D, Moradi, Ghobad, Moradi, Masoud, Moradi-Joo, Mohammad, Moradi-Lakeh, Maziar, Moradzadeh, Rahmatollah, Moraga, Paula, Moreno Velásquez, Ilai, Morgado-da-Costa, Joana, Morrison, Shane Dougla, Mosser, Jonathan F, Mouodi, Simin, Mousavi, Seyyed Meysam, Mousavi Khaneghah, Amin, Mueller, Ulrich Otto, Musa, Kamarul Imran, Muthupandian, Saravanan, Nabavizadeh, Behnam, Naderi, Mehdi, Nagarajan, Ahamarshan Jayaraman, Naghavi, Mohsen, Naghshtabrizi, Behshad, Naik, Gurudatta, Najafi, Farid, Nangia, Vinay, Nansseu, Jobert Richie, Ndwandwe, Duduzile Edith, Negoi, Ionut, Negoi, Ruxandra Irina, Ngunjiri, Josephine W, Nguyen, Huong Lan Thi, Nguyen, Trang Huyen, Nigatu, Yeshambel T, Nikbakhsh, Rajan, Nikpoor, Amin Reza, Nixon, Molly R, Nnaji, Chukwudi A, Nomura, Shuhei, Noubiap, Jean Jacque, Nouraei Motlagh, Soraya, Nowak, Christoph, Oţoiu, Adrian, Odell, Christopher M, Oh, In-Hwan, Oladnabi, Morteza, Olagunju, Andrew T, Olusanya, Bolajoko Olubukunola, Olusanya, Jacob Olusegun, Omar Bali, Ahmed, Ong, Kanyin L, Onwujekwe, Obinna E, Ortiz, Alberto, Otstavnov, Nikita, Otstavnov, Stanislav S, Øverland, Simon, Owolabi, Mayowa O, P A, Mahesh, Padubidri, Jagadish Rao, Pakshir, Keyvan, Palladino, Raffaele, Pana, Adrian, Panda-Jonas, Songhomitra, Park, Jame, Pasupula, Deepak Kumar, Patel, Jenil R, Patel, Sangram Kishor, Patton, George C, Paulson, Katherine R, Pazoki Toroudi, Hamidreza, Pease, Spencer A, Peden, Amy E, Pepito, Veincent Christian Filipino, Peprah, Emmanuel K, Pereira, Alexandre, Pereira, David M, Perico, Norberto, Pigott, David M, Pilgrim, Thoma, Pilz, Tessa M, Piradov, Michael A, Pirsaheb, Meghdad, Pokhrel, Khem Narayan, Postma, Maarten J, Pourjafar, Hadi, Pourmalek, Farshad, Pourshams, Akram, Poznańska, Anna, Prada, Sergio I, Prakash, Sanjay, Preotescu, Liliana, Quazi Syed, Zahiruddin, Rabiee, Mohammad, Rabiee, Navid, Radfar, Amir, Rafiei, Alireza, Raggi, Alberto, Rahman, Muhammad Aziz, Rajabpour-Sanati, Ali, Ram, Pradhum, Ranabhat, Chhabi Lal, Rao, Sowmya J, Rasella, Davide, Rashedi, Vahid, Rastogi, Prateek, Rathi, Priya, Rawal, Lal, Remuzzi, Giuseppe, Renjith, Vishnu, Renzaho, Andre M N, Resnikoff, Serge, Rezaei, Nima, Rezai, Mohammad sadegh, Rezapour, Aziz, Rickard, Jennifer, Roever, Leonardo, Ronfani, Luca, Roshandel, Gholamreza, Rostamian, Morteza, Rubagotti, Enrico, Rwegerera, Godfrey M, Sabour, Siamak, Saddik, Basema, Sadeghi, Ehsan, Sadeghi, Masoumeh, Saeedi Moghaddam, Sahar, Safari, Yahya, Safi, Sare, Safiri, Saeid, Sagar, Rajesh, Sahebkar, Amirhossein, Sahraian, Mohammad Ali, Sajadi, S Mohammad, Salahshoor, Mohammad Reza, Salama, Joseph S, Salamati, Payman, Salem, Marwa R Rashad, Salimi, Yahya, Salomon, Joshua A, Salz, Inbal, Samad, Zainab, Samy, Abdallah M, Sanabria, Juan, Santric-Milicevic, Milena M, Saraswathy, Sivan Yegnanarayana Iyer, Sartorius, Benn, Sarveazad, Arash, Sathian, Brijesh, Sathish, Thirunavukkarasu, Sattin, Davide, Saylan, Mete, Schaeffer, Lauren E, Schiavolin, Silvia, Schwebel, David C, Schwendicke, Falk, Sekerija, Mario, Senbeta, Anbissa Muleta, Senthilkumaran, Subramanian, Sepanlou, Sadaf G, Serván-Mori, Edson, Shabani, Mahsima, Shahabi, Saeed, Shahbaz, Mohammad, Shaheen, Amira A, Shaikh, Masood Ali, Shalash, Ali S, Shams-Beyranvand, Mehran, Shamsi, Mohammadbagher, Shamsizadeh, Morteza, Shannawaz, Mohammed, Sharafi, Kiomar, Sharafi, Zeinab, Sharara, Fablina, Sharma, Rajesh, Shaw, David H, Sheikh, Aziz, Shin, Jae Il, Shiri, Rahman, Shrime, Mark G, Shuval, Kerem, Siabani, Soraya, Sigfusdottir, Inga Dora, Sigurvinsdottir, Rannveig, Silva, Diego Augusto Santo, Simonetti, Biagio, Simpson, Kyle E, Singh, Jasvinder A, Skiadaresi, Eirini, Skryabin, Valentin Yurievich, Soheili, Amin, Sokhan, Anton, Sorensen, Reed J D, Soriano, Joan B, Sorrie, Muluken Bekele, Soyiri, Ireneous N, Spurlock, Emma Elizabeth, Sreeramareddy, Chandrashekhar T, Stockfelt, Leo, Stokes, Mark A, Stubbs, Jacob L, Sudaryanto, Agu, Sufiyan, Mu'awiyyah Babale, Suliankatchi Abdulkader, Rizwan, Sykes, Bryan L, Tabarés-Seisdedos, Rafael, Tabb, Karen M, Tadakamadla, Santosh Kumar, Taherkhani, Amir, Tang, Muming, Taveira, Nuno, Taylor, Heather Jean, Teagle, Whitney L, Tehrani-Banihashemi, Arash, Teklehaimanot, Berhane Fseha, Tessema, Zemenu Tadesse, Thankappan, Kavumpurathu Raman, Thomas, Nihal, Thrift, Amanda G, Titova, Mariya Vladimirovna, Tohidinik, Hamid Reza, Tonelli, Marcello, Topor-Madry, Roman, Topouzis, Foti, Tovani-Palone, Marcos Roberto Roberto, Traini, Eugenio, Tran, Bach Xuan, Travillian, Ravensara, Trias-Llimós, Sergi, Truelsen, Thomas Clement, Tudor Car, Lorainne, Unnikrishnan, Bhaskaran, Upadhyay, Era, Vacante, Marco, Vakilian, Alireza, Valdez, Pascual R, Valli, Alessandro, Vardavas, Constantine, Vasankari, Tommi Juhani, Vasconcelos, Ana Maria Nogale, Vasseghian, Yasser, Veisani, Yousef, Venketasubramanian, Narayanaswamy, Vidale, Simone, Violante, Francesco S, Vlassov, Vasily, Vollset, Stein Emil, Vos, Theo, Vujcic, Isidora S, Vukovic, Ana, Vukovic, Rade, Waheed, Yasir, Wallin, Mitchell Taylor, Walters, Magdalene K, Wang, Hongbo, Wang, Yuan-Pang, Watson, Stefanie, Wei, Jingkai, Weiss, Jordan, Weldesamuel, Girmay Teklay, Werdecker, Andrea, Westerman, Ronny, Whiteford, Harvey A, Wiangkham, Taweewat, Wiens, Kirsten E, Wijeratne, Tissa, Wiysonge, Charles Shey, Wojtyniak, Bogdan, Wolfe, Charles D A, Wondmieneh, Adam Belay, Wool, Eve E, Wu, Ai-Min, Wu, Junjie, Xu, Gelin, Yamada, Tomohide, Yamagishi, Kazumasa, Yano, Yuichiro, Yaya, Sanni, Yazdi-Feyzabadi, Vahid, Yearwood, Jamal A, Yeheyis, Tomas Y, Yilgwan, Christopher Sabo, Yip, Paul, Yonemoto, Naohiro, Yoon, Seok-Jun, Yoosefi Lebni, Javad, York, Hunter W, Younis, Mustafa Z, Younker, Theodore Patrick, Yousefi, Zabihollah, Yousefinezhadi, Taraneh, Yousuf, Abdilahi Yousuf, Yusefzadeh, Hasan, Zahirian Moghadam, Telma, Zakzuk, Josefina, Zaman, Sojib Bin, Zamani, Mohammad, Zamanian, Maryam, Zandian, Hamed, Zhang, Zhi-Jiang, Zheng, Peng, Zhou, Maigeng, Ziapour, Arash, Murray, Christopher J L, Collaborators, GBD 2019 Demographics, GBD 2019 Demographics Collaborator, Violante FS, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Microbes in Health and Disease (MHD), Department of Earth Systems Analysis, Biomechanical Engineering, TechMed Centre, Biomolecular Nanotechnology, Research Methodology, Measurement and Data Analysis, Materials Science and Technology of Polymers, Inorganic Materials Science, MESA+ Institute, Biomedical and Environmental Sensorsystems, Mesoscale Chemical Systems, Faculty of Engineering Technology, Nonlinear Solid Mechanics, Digital Society Institute, Pervasive Systems, Nanobiophysics, Faculty of Geo-Information Science and Earth Observation, Multi Scale Mechanics, Engineering Fluid Dynamics, Physics of Complex Fluids, Developmental BioEngineering, Physics of Fluids, Elastomer Technology and Engineering, Medical Cell Biophysics, European Membrane Institute, Department of Earth Observation Science, Biomaterials Science and Technology, Sustainable Process Technology, Department of Urban and Regional Planning and Geo-Information Management, Department of Natural Resources, XUV Optics, Databases (Former), Department of Water Resources, Psychology, Health & Technology, Membrane Science & Technology, Department of Public Health, Clinicum, HUS Neurocenter, HUS Comprehensive Cancer Center, and Environmental Sciences
Subjects: Male, very elderly, Demographic transition, HALE, 030204 cardiovascular system & hematology, preschool child, Global Burden of Disease, Carga Global de Enfermedades, 0302 clinical medicine, newborn, Risk Factors, Surveys and Questionnaires, and Risk Factors Study, 80 and over, 030212 general & internal medicine, Birth Rate, Child, Migration, 11 Medical and Health Sciences, Aged, 80 and over, education.field_of_study, Injuries, Geography, Mortality rate, 1. No poverty, DEATH, Censuses, General Medicine, SDG 10 - Reduced Inequalities, Middle Aged, Demographic analysis, 3142 Public health care science, environmental and occupational health, 3. Good health, demographic analysis, Estilo de Vida Saludable, risk factor, Child, Preschool, Demography/statistics & numerical data, Global Burden of Diseases, Injuries, Risk Factors, Fertility, Mortality, Migration, Population, epidemiology, Female, A990 Medicine and Dentistry not elsewhere classified, CHILD-MORTALITY, Live Birth, Global Health Metrics, TRANSITION, demographics, GBD, fertility, mortality, hale, Adult, Adolescent, Total fertility rate, Population, Global Burden of Diseases, Injuries, and Risk Factors Study, Birth rate, 03 medical and health sciences, Young Adult, Life Expectancy, SDG 3 - Good Health and Well-being, General & Internal Medicine, SYSTEMATIC ANALYSIS, Demografía, Humans, Global Burden of Disease Study, human, Mortality, education, Preschool, Aged, Demography, Spatial Analysis, questionnaire, Infant, Newborn, Klinisk medicin, HIV, Infant, Global Burden of Diseases, sex-specific fertility, Live Birth/epidemiology, purl.org/pe-repo/ocde/ford#3.02.00 [https], MODEL, Fertilidad, Fertility, Demographic change, Life expectancy, NA, global disease burden, Clinical Medicine, population research
Abstract: Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings The global TFR decreased from 2.72 (95% uncertainty interval [UI] 2.66-2.79) in 2000 to 2.31 (2.17-2.46) in 2019. Global annual livebirths increased from 134.5 million (131.5-137.8) in 2000 to a peak of 139.6 million (133.0-146.9) in 2016. Global livebirths then declined to 135.3 million (127.2-144.1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2.1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27.1% (95% UI 26.4-27.8) of global livebirths. Global life expectancy at birth increased from 67.2 years (95% UI 66.8-67.6) in 2000 to 73.5 years (72.8-74.3) in 2019. The total number of deaths increased from 50.7 million (49.5-51.9) in 2000 to 56.5 million (53.7-59.2) in 2019. Under-5 deaths declined from 9.6 million (9.1-10.3) in 2000 to 5.0 million (4.3-6.0) in 2019. Global population increased by 25.7%, from 6.2 billion (6.0-6.3) in 2000 to 7.7 billion (7.5-8.0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58.6 years (56.1-60.8) in 2000 to 63.5 years (60.8-66.1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
Published: 2020

10. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author: Sønderby, I.E., Ching, CRK, Thomopoulos, S.I., van der Meer, D., Sun, D., Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa-Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, EWC, Cichon, S., Ciufolini, S., Craig, M.C., Crespo-Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., de Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J.J., Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, EEM, Kushan, L., Linden, DEJ, Liu, J., Lundervold, A.J., Martin-Brevet, S., Martínez, K., Mather, K.A., Mathias, S.R., McDonald-McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez-Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefansson, H., Stein, D.J., Tamnes, C.K., Tordesillas-Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., van 't Ent, D., van den Bree, MBM, Vassos, E., Vázquez-Bourgon, J., Vila-Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., Andreassen, O.A., ENIGMA-CNV Working Group, ENIGMA 22q11.2 Deletion Syndrome Working Group, Bernard, M., Blackburn, N.B., Bøen, R., de Geus, E., de Zwarte, SMC, Forti, M.D., Frei, O., Fukunaga, M., Hehir-Kwa, J.Y., Hillegers, MHJ, Hoffmann, P., Homuth, G., Jahanshad, N., Koops, S., Kumar, K., Kikuchi, M., Le Hellard, S., Leu, C., Murray, R.M., Naerland, T., Nyberg, L., Ophoff, R.A., Pike, G.B., Sando, S.B., Shin, J., Shumskaya, E., Sisodiya, S.M., Steen, V.M., Teumer, A., Uhlmann, A., Wright, M.J., Antshel, K.M., Campbell, L.E., Crossley, N.A., Crowley, T.B., Daly, E., Fiksinski, A.M., Forsyth, J.K., Fremont, W., Goodrich-Hunsaker, N.J., Gudbrandsen, M., Jonas, R.K., Kates, W.R., Lin, A., McCabe, K.L., Moss, H., Murphy, D.G., Murphy, K.C., Owen, M.J., Ruparel, K., Simon, T.J., van Amelsvoort, T., and Vorstman, JAS
Subjects: brain structural imaging, copy number variant, diffusion tensor imaging, evolution, genetics-first approach, neurodevelopmental disorders, psychiatric disorders
Abstract: The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2022

11. The relationship of current depressive symptoms and past depression with cognitive impairment and instrumental activities of daily living in an elderly population: The Sydney Memory and Ageing Study

Author: Reppermund, S., Brodaty, H., Crawford, J.D., Kochan, N.A., Slavin, M.J., Trollor, J.N., Draper, B., and Sachdev, P.S.
Published: 2011
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12. Sex differences in the causes and consequences of white matter hyperintensities

Author: Sachdev, P.S., Parslow, R., Wen, W., Anstey, K.J., and Easteal, S.
Published: 2009
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13. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author: Ahluwalia, T.S., Prins, B.P., Abdollahi, M., Armstrong, N.J., Aslibekyan, S., Bain, L., Jefferis, B., Baumert, J., Beekman, M., Ben-Shlomo, Y., Bis, J.C., Mitchell, B.D., Geus, E. de, Delgado, G.E., Marek, D., Eriksson, J., Kajantie, E., Kanoni, S., Kemp, J.P., Lu, C., Marioni, R.E., McLachlan, S., Milaneschi, Y., Nolte, I.M., Petrelis, A.M., Porcu, E., Sabater-Lleal, M., Naderi, E., Seppala, I., Shah, T., Singhal, G., Standl, M., Teumer, A., Thalamuthu, A., Thiering, E., Trompet, S., Ballantyne, C.M., Benjamin, E.J., Casas, J.P., Toben, C., Dedoussis, G., Deelen, J., Durda, P., Engmann, J., Feitosa, M.F., Grallert, H., Hammarstedt, A., Harris, S.E., Homuth, G., Hottenga, J.J., Jalkanen, S., Jamshidi, Y., Jawahar, M.C., Jess, T., Kivimaki, M., Kleber, M.E., Lahti, J., Liu, Y., Marques-Vidal, P., Mellstrom, D., Mooijaart, S.P., Muller-Nurasyid, M., Penninx, B., Revez, J.A., Rossing, P., Raikkonen, K., Sattar, N., Scharnagl, H., Sennblad, B., Silveira, A., St Pourcain, B., Timpson, N.J., Trollor, J., Dongen, J. van, Heemst, D. van, Visvikis-Siest, S., Vollenweider, P., Volker, U., Waldenberger, M., Willemsen, G., Zabaneh, D., Morris, R.W., Arnett, D.K., Baune, B.T., Boomsma, D.I., Chang, Y.P.C., Deary, I.J., Deloukas, P., Eriksson, J.G., Evans, D.M., Ferreira, M.A., Gaunt, T., Gudnason, V., Hamsten, A., Heinrich, J., Hingorani, A., Humphries, S.E., Jukema, J.W., Koenig, W., Kumari, M., Kutalik, Z., Lawlor, D.A., Lehtimaki, T., Marz, W., Mather, K.A., Naitza, S., Nauck, M., Ohlsson, C., Price, J.F., Raitakari, O., Rice, K., Sachdev, P.S., Slagboom, E., Sorensen, T.I.A., Spector, T., Stacey, D., Stathopoulou, M.G., Tanaka, T., Wannamethee, S.G., Whincup, P., Rotter, J.I., Dehghan, A., Boerwinkle, E., Psaty, B.M., Snieder, H., Alizadeh, B.Z., and CHARGE Inflammation Working Grp
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021

14. Investigating olfactory gene variation and odour identification in older adults

Author: Raj, S., Thalamuthu, A., Armstrong, N.J., Wright, M.J., Kwok, J.B., Trollor, J.N., Ames, D., Schofield, P.R., Brodaty, H., Sachdev, P.S., Mather, K.A., Raj, S., Thalamuthu, A., Armstrong, N.J., Wright, M.J., Kwok, J.B., Trollor, J.N., Ames, D., Schofield, P.R., Brodaty, H., Sachdev, P.S., and Mather, K.A.
Abstract: Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data (n = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer’s disease (AD), white matter hyperintensities (WMH), Parkinson’s disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes (n = 967), previously identified candidate olfaction-related SNPs (n = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.
Published: 2021

15. Polygenic risk score analysis for amyotrophic lateral sclerosis leveraging cognitive performance, educational attainment and schizophrenia

Author: Restuadi, R., Garton, F.C., Benyamin, B., Lin, T., Williams, K.L., Vinkhuyzen, A., van Rheenen, W., Zhu, Z., Laing, N.G., Mather, K.A., Sachdev, P.S., Ngo, S.T., Steyn, F.J., Wallace, L., Henders, A.K., Visscher, P.M., Needham, M., Mathers, S., Nicholson, G., Rowe, D.B., Henderson, R.D., McCombe, P.A., Pamphlett, R., Blair, I.P., Wray, N.R., McRae, A.F., Restuadi, R., Garton, F.C., Benyamin, B., Lin, T., Williams, K.L., Vinkhuyzen, A., van Rheenen, W., Zhu, Z., Laing, N.G., Mather, K.A., Sachdev, P.S., Ngo, S.T., Steyn, F.J., Wallace, L., Henders, A.K., Visscher, P.M., Needham, M., Mathers, S., Nicholson, G., Rowe, D.B., Henderson, R.D., McCombe, P.A., Pamphlett, R., Blair, I.P., Wray, N.R., and McRae, A.F.
Abstract: Amyotrophic Lateral Sclerosis (ALS) is recognised to be a complex neurodegenerative disease involving both genetic and non-genetic risk factors. The underlying causes and risk factors for the majority of cases remain unknown; however, ever-larger genetic data studies and methodologies promise an enhanced understanding. Recent analyses using published summary statistics from the largest ALS genome-wide association study (GWAS) (20,806 ALS cases and 59,804 healthy controls) identified that schizophrenia (SCZ), cognitive performance (CP) and educational attainment (EA) related traits were genetically correlated with ALS. To provide additional evidence for these correlations, we built single and multi-trait genetic predictors using GWAS summary statistics for ALS and these traits, (SCZ, CP, EA) in an independent Australian cohort (846 ALS cases and 665 healthy controls). We compared methods for generating the risk predictors and found that the combination of traits improved the prediction (Nagelkerke-R2) of the case–control logistic regression. The combination of ALS, SCZ, CP, and EA, using the SBayesR predictor method gave the highest prediction (Nagelkerke-R2) of 0.027 (P value = 4.6 × 10−8), with the odds-ratio for estimated disease risk between the highest and lowest deciles of individuals being 3.15 (95% CI 1.96–5.05). These results support the genetic correlation between ALS, SCZ, CP and EA providing a better understanding of the complexity of ALS.
Published: 2021

16. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Andreassen, O.A., Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., and Andreassen, O.A.
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

17. Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders

Author: Nabais, M.F., Laws, S.M., Lin, T., Vallerga, C.L., Armstrong, N.J., Blair, I.P., Kwok, J.B., Mather, K.A., Mellick, G.D., Sachdev, P.S., Wallace, L., Henders, A.K., Zwamborn, R.A.J., Hop, P.J., Lunnon, K., Pishva, E., Roubroeks, J.A.Y., Soininen, H., Tsolaki, M., Mecocci, P., Lovestone, S., Kłoszewska, I., Vellas, B., Furlong, S., Garton, F.C., Henderson, R.D., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Anderson, T.J., Bentley, S.R., Dalrymple-Alford, J., Fowder, J., Gratten, J., Halliday, G., Hickie, I.B., Kennedy, M., Lewis, S.J.G., Montgomery, G.W., Pearson, J., Pitcher, T.L., Silburn, P., Zhang, F., Visscher, P.M., Yang, J., Stevenson, A.J., Hillary, R.F., Marioni, R.E., Harris, S.E., Deary, I.J., Jones, A.R., Shatunov, A., Iacoangeli, A., van Rheenen, W., van den Berg, L.H., Shaw, P.J., Shaw, C.E., Morrison, K.E., Al-Chalabi, A., Veldink, J.H., Hannon, E., Mill, J., Wray, N.R., McRae, A.F., Nabais, M.F., Laws, S.M., Lin, T., Vallerga, C.L., Armstrong, N.J., Blair, I.P., Kwok, J.B., Mather, K.A., Mellick, G.D., Sachdev, P.S., Wallace, L., Henders, A.K., Zwamborn, R.A.J., Hop, P.J., Lunnon, K., Pishva, E., Roubroeks, J.A.Y., Soininen, H., Tsolaki, M., Mecocci, P., Lovestone, S., Kłoszewska, I., Vellas, B., Furlong, S., Garton, F.C., Henderson, R.D., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Anderson, T.J., Bentley, S.R., Dalrymple-Alford, J., Fowder, J., Gratten, J., Halliday, G., Hickie, I.B., Kennedy, M., Lewis, S.J.G., Montgomery, G.W., Pearson, J., Pitcher, T.L., Silburn, P., Zhang, F., Visscher, P.M., Yang, J., Stevenson, A.J., Hillary, R.F., Marioni, R.E., Harris, S.E., Deary, I.J., Jones, A.R., Shatunov, A., Iacoangeli, A., van Rheenen, W., van den Berg, L.H., Shaw, P.J., Shaw, C.E., Morrison, K.E., Al-Chalabi, A., Veldink, J.H., Hannon, E., Mill, J., Wray, N.R., and McRae, A.F.
Abstract: Background People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. Results We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson’s disease (and none with Alzheimer’s disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights. Conclusions We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.
Published: 2021

18. Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs

Author: Sønderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D., Sun, D., Villalon‐Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa‐Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, E.W.C., Cichon, S., Ciufolini, S., Craig, M.C., Crespo‐Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J‐J, Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, E.E.M., Kushan, L., Linden, D.E.J., Liu, J., Lundervold, A.J., Martin‐Brevet, S., Martinez, K., Mather, K.A., Mathias, S.R., McDonald‐McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez‐Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefánsson, H., Stein, D.J., Tamnes, C.K., Tordesillas‐Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., Ent, D., Bree, M.B.M., Vassos, E., Vázquez‐Bourgon, J., Vila‐Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., Andreassen, O.A., Sønderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D., Sun, D., Villalon‐Reina, J.E., Agartz, I., Amunts, K., Arango, C., Armstrong, N.J., Ayesa‐Arriola, R., Bakker, G., Bassett, A.S., Boomsma, D.I., Bülow, R., Butcher, N.J., Calhoun, V.D., Caspers, S., Chow, E.W.C., Cichon, S., Ciufolini, S., Craig, M.C., Crespo‐Facorro, B., Cunningham, A.C., Dale, A.M., Dazzan, P., Zubicaray, G.I., Djurovic, S., Doherty, J.L., Donohoe, G., Draganski, B., Durdle, C.A., Ehrlich, S., Emanuel, B.S., Espeseth, T., Fisher, S.E., Ge, T., Glahn, D.C., Grabe, H.J., Gur, R.E., Gutman, B.A., Haavik, J., Håberg, A.K., Hansen, L.A., Hashimoto, R., Hibar, D.P., Holmes, A.J., Hottenga, J‐J, Hulshoff Pol, H.E., Jalbrzikowski, M., Knowles, E.E.M., Kushan, L., Linden, D.E.J., Liu, J., Lundervold, A.J., Martin‐Brevet, S., Martinez, K., Mather, K.A., Mathias, S.R., McDonald‐McGinn, D.M., McRae, A.F., Medland, S.E., Moberget, T., Modenato, C., Monereo Sánchez, J., Moreau, C.A., Mühleisen, T.W., Paus, T., Pausova, Z., Prieto, C., Ragothaman, A., Reinbold, C.S., Reis Marques, T., Repetto, G.M., Reymond, A., Roalf, D.R., Rodriguez‐Herreros, B., Rucker, J.J., Sachdev, P.S., Schmitt, J.E., Schofield, P.R., Silva, A.I., Stefánsson, H., Stein, D.J., Tamnes, C.K., Tordesillas‐Gutiérrez, D., Ulfarsson, M.O., Vajdi, A., Ent, D., Bree, M.B.M., Vassos, E., Vázquez‐Bourgon, J., Vila‐Rodriguez, F., Walters, G.B., Wen, W., Westlye, L.T., Wittfeld, K., Zackai, E.H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Bearden, C.E., and Andreassen, O.A.
Abstract: The Enhancing NeuroImaging Genetics through Meta‐Analysis copy number variant (ENIGMA‐CNV) and 22q11.2 Deletion Syndrome Working Groups (22q‐ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA‐CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q‐ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest‐ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi‐site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene‐dosage effects on distinct brain regions also emerged, providing further insight into genotype–phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This “genotype‐first” approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
Published: 2021

19. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author: Frangou, S. (Sophia), Modabbernia, A. (Amirhossein), Williams, S.C.R. (Steven C. R.), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L. (Lisa), Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), Ent, D. (Dennis) van 't, Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), Dima, D. (Danai), Frangou, S. (Sophia), Modabbernia, A. (Amirhossein), Williams, S.C.R. (Steven C. R.), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L. (Lisa), Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), Ent, D. (Dennis) van 't, Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), and Dima, D. (Danai)
Abstract: Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
Published: 2021
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20. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Author: van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., Veldink, J.H., van Rheenen, W., van der Spek, R.A.A., Bakker, M.K., van Vugt, J.J.F.A., Hop, P.J., Zwamborn, R.A.J., de Klein, N., Westra, H-J, Bakker, O.B., Deelen, P., Shireby, G., Hannon, E., Moisse, M., Baird, D., Restuadi, R., Dolzhenko, E., Dekker, A.M., Gawor, K., Westeneng, H-J, Tazelaar, G.H.P., van Eijk, K.R., Kooyman, M., Byrne, R.P., Doherty, M., Heverin, M., Al Khleifat, A., Iacoangeli, A., Shatunov, A., Ticozzi, N., Cooper-Knock, J., Smith, B.N., Gromicho, M., Chandran, S., Pal, S., Morrison, K.E., Shaw, P.J., Hardy, J., Orrell, R.W., Sendtner, M., Meyer, T., Başak, N., van der Kooi, A.J., Ratti, A., Fogh, I., Gellera, C., Lauria, G., Corti, S., Cereda, C., Sproviero, D., D’alfonso, S., Sorarù, G., Siciliano, G., Filosto, M., Padovani, A., Chio, A., Calvo, A., Moglia, C., Brunetti, M., Canosa, A., Grassano, M., Beghi, E., Pupillo, E., Logroscino, G., Nefussy, B., Osmanovic, A., Nordin, A., Lerner, Y., Zabari, M., Gotkine, M., Baloh, R.H., Bell, S., Vourc’h, P., Corcia, P., Couratier, P., Millecamps, S., Meininger, V., Salachas, F., Mora Pardina, J.S., Assialioui, A., Rojas-García, R., Dion, P.A., Ross, J.P., Ludolph, A.C., Weishaupt, J.H., Brenner, D., Freischmidt, A., Bensimon, G., Brice, A., Durr, A., Payan, C.A.M., Saker-Delye, S., Wood, N.W., Topp, S., Rademakers, R., Tittmann, L., Lieb, W., Franke, A., Ripke, S., Braun, A., Kraft, J., Whiteman, D.C., Olsen, C.M., Uitterlinden, A.G., Hofman, A., Rietschel, M., Cichon, S., Nöthen, M.M., Amouyel, P., Comi, G., Riva, N., Lunetta, C., Gerardi, F., Cotelli, M.S., Rinaldi, F., Chiveri, L., Guaita, M.C., Perrone, P., Ceroni, M., Diamanti, L., Ferrarese, C., Tremolizzo, L., Delodovici, M.L., Bono, G., Manera, U., Vasta, R., Bombaci, A., Casale, F., Fuda, G., Salamone, P., Iazzolino, B., Peotta, L., Cugnasco, P., De Marco, G., Torrieri, M.C., Palumbo, F., Gallone, S., Barberis, M., Sbaiz, L., Gentile, S., Mauro, A., Mazzini, L., De Marchi, F., Corrado, L., D’Alfonso, S., Bertolotto, A., Gionco, M., Leotta, D., Odddenino, E., Imperiale, D., Cavallo, R., Pignatta, P., De Mattei, M., Geda, C., Papurello, D.M., Gusmaroli, G., Comi, C., Labate, C., Ruiz, L., Ferrandi, D., Rota, E., Aguggia, M., Di Vito, N., Meineri, P., Ghiglione, P., Launaro, N., Dotta, M., di Sapio, A., Giardini, G., Tiloca, C., Peverelli, S., Taroni, F., Pensato, V., Castellotti, B., Comi, G.P., Del Bo, R., Gagliardi, S., Raggi, F., Simoncini, C., Lo Gerfo, A., Inghilleri, M., Ferlini, A., Simone, I.L., Passarella, B., Guerra, V., Zoccolella, S., Nozzoli, C., Mundi, C., Leone, M., Zarrelli, M., Tamma, F., Valluzzi, F., Calabrese, G., Boero, G., Rini, A., Traynor, B.J., Singleton, A.B., Mitne Neto, M., Cauchi, R.J., Ophoff, R.A., Wiedau-Pazos, M., Lomen-Hoerth, C., van Deerlin, V.M., Grosskreutz, J., Roediger, A., Gaur, N., Jörk, A., Barthel, T., Theele, E., Ilse, B., Stubendorff, B., Witte, O.W., Steinbach, R., Hübner, C.A., Graff, C., Brylev, L., Fominykh, V., Demeshonok, V., Ataulina, A., Rogelj, B., Koritnik, B., Zidar, J., Ravnik-Glavač, M., Glavač, D., Stević, Z., Drory, V., Povedano, M., Blair, I.P., Kiernan, M.C., Benyamin, B., Henderson, R.D., Furlong, S., Mathers, S., McCombe, P.A., Needham, M., Ngo, S.T., Nicholson, G.A., Pamphlett, R., Rowe, D.B., Steyn, F.J., Williams, K.L., Mather, K.A., Sachdev, P.S., Henders, A.K., Wallace, L., de Carvalho, M., Pinto, S., Petri, S., Weber, M., Rouleau, G.A., Silani, V., Curtis, C.J., Breen, G., Glass, J.D., Brown, R.H., Landers, J.E., Shaw, C.E., Andersen, P.M., Groen, E.J.N., van Es, M.A., Pasterkamp, R.J., Fan, D., Garton, F.C., McRae, A.F., Davey Smith, G., Gaunt, T.R., Eberle, M.A., Mill, J., McLaughlin, R.L., Hardiman, O., Kenna, K.P., Wray, N.R., Tsai, E., Runz, H., Franke, L., Al-Chalabi, A., Van Damme, P., van den Berg, L.H., and Veldink, J.H.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
Published: 2021

21. Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

Author: Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, Nicola, Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J.L., Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., Desrivières, S., Jia, T., Chu, C., Liu, Y., van Dongen, J., Papastergios, E., Armstrong, Nicola, Bastin, M.E., Carrillo-Roa, T., den Braber, A., Harris, M., Jansen, R., Liu, J., Luciano, M., Ori, A.P.S., Roiz Santiañez, R., Ruggeri, B., Sarkisyan, D., Shin, J., Sungeun, K., Tordesillas Gutiérrez, D., van’t Ent, D., Ames, D., Artiges, E., Bakalkin, G., Banaschewski, T., Bokde, A.L.W., Brodaty, H., Bromberg, U., Brouwer, R., Büchel, C., Burke Quinlan, E., Cahn, W., de Zubicaray, G.I., Ehrlich, S., Ekström, T.J., Flor, H., Fröhner, J.H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Hoare, J., Ittermann, B., Jahanshad, N., Jiang, J., Kwok, J.B., Martin, N.G., Martinot, J.L., Mather, K.A., McMahon, K.L., McRae, A.F., Nees, F., Papadopoulos Orfanos, D., Paus, T., Poustka, L., Sämann, P.G., Schofield, P.R., Smolka, M.N., Stein, D.J., Strike, L.T., Teeuw, J., Thalamuthu, A., Trollor, J., Walter, H., Wardlaw, J.M., Wen, W., Whelan, R., Apostolova, L.G., Binder, E.B., Boomsma, D.I., Calhoun, V., Crespo-Facorro, B., Deary, I.J., Hulshoff Pol, H., Ophoff, R.A., Pausova, Z., Sachdev, P.S., Saykin, A., Wright, M.J., Thompson, P.M., Schumann, G., and Desrivières, S.
Abstract: DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)—three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.
Published: 2021

22. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M., Suzuki, H., Jian, X.Q., Sarnowski, C., Evans, T.E., Bis, J.C., Eiriksdottir, G., Sakaue, S., Terzikhan, N., Habes, M., Zhao, W., Armstrong, N.J., Hofer, E., Yanek, L.R., Hagenaars, S.P., Kumar, R.B., Akker, E.B. van den, McWhirter, R.E., Trompet, S., Mishra, A., Saba, Y., Satizabal, C.L., Beaudet, G., Petit, L., Tsuchida, A., Zago, L., Schilling, S., Sigurdsson, S., Gottesman, R.F., Lewis, C.E., Aggarwal, N.T., Lopez, O.L., Smith, J.A., Hernandez, M.C.V., Grond, J. van der, Wright, M.J., Knol, M.J., Dorr, M., Thomson, R.J., Bordes, C., Grand, Q. le, Duperron, M.G., Smith, A.V., Knopman, D.S., Schreiner, P.J., Evans, D.A., Rotter, J.I., Beiser, A.S., Maniega, S.M., Beekman, M., Trollor, J., Stott, D.J., Vernooij, M.W., Wittfeld, K., Niessen, W.J., Soumare, A., Boerwinkle, E., Sidney, S., Turner, S.T., Davies, G., Thalamuthu, A., Volker, U., Buchem, M.A. van, Bryan, R.N., Dupuis, J., Bastin, M.E., Ames, D., Teumer, A., Amouyel, P., Kwok, J.B., Bulow, R., Deary, I.J., Schofield, P.R., Brodaty, H., Jiang, J.Y., Tabara, Y., Setoh, K., Miyamoto, S., Yoshida, K., Nagata, M., Kamatani, Y., Matsuda, F., Psaty, B.M., Bennett, D.A., Jager, P.L. de, Mosley, T.H., Sachdev, P.S., Schmidt, R., Warren, H.R., Evangelou, E., Tregouet, D.A., Ikram, M.A., Wen, W., DeCarli, C., Srikanth, V.K., Jukema, J.W., Slagboom, E.P., Kardia, S.L.R., Okada, Y., Mazoyer, B., Wardlaw, J.M., Nyquist, P.A., Mather, K.A., Grabe, H.J., Schmidt, H., Duijn, C.M. van, Gudnason, V., Longstreth, W.T., Launer, L.J., Lathrop, M., Seshadri, S., Tzourio, C., Adams, H.H., Matthews, P.M., Fornage, M., Debette, S., Int Network Thrombosis INVENT Cons, and Int Headache Genomics Consortium I
Subjects: Adult, Male, Science, BLOOD-PRESSURE, Risk Assessment, behavioral disciplines and activities, GENETIC ARCHITECTURE, Young Adult, Alzheimer Disease, Risk Factors, mental disorders, WHITE-MATTER HYPERINTENSITIES, WIDE ASSOCIATION, Humans, International Headache Genomics Consortium (IHGC), CELL-TYPES, Medical History Taking, METAANALYSIS, AGING RESEARCH, Aged, RISK, Aged, 80 and over, Science & Technology, Mendelian Randomization Analysis, Middle Aged, COGNITIVE IMPAIRMENT, White Matter, Multidisciplinary Sciences, Stroke, Diffusion Tensor Imaging, Genetic Loci, Cerebral Small Vessel Diseases, Hypertension, MENDELIAN RANDOMIZATION, Science & Technology - Other Topics, Female, International Network against Thrombosis (INVENT) Consortium, Genome-Wide Association Study
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p=2.5x10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials. White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.
Published: 2020

23. Does parity matter in women's risk of dementia? A COSMIC collaboration cohort study

Author: Bae, J.B. Lipnicki, D.M. Han, J.W. Sachdev, P.S. Kim, T.H. Kwak, K.P. Kim, B.J. Kim, S.G. Kim, J.L. Moon, S.W. Park, J.H. Ryu, S.-H. Youn, J.C. Lee, D.Y. Lee, D.W. Lee, S.B. Lee, J.J. Jhoo, J.H. Llibre-Rodriguez, J.J. Llibre-Guerra, J.J. Valhuerdi-Cepero, A.J. Ritchie, K. Ancelin, M.-L. Carriere, I. Skoog, I. Najar, J. Sterner, T.R. Scarmeas, N. Yannakoulia, M. Dardiotis, E. Meguro, K. Kasai, M. Nakamura, K. Riedel-Heller, S. Roehr, S. Pabst, A. Van Boxtel, M. Köhler, S. Ding, D. Zhao, Q. Liang, X. Scazufca, M. Lobo, A. De-La-Cámara, C. Lobo, E. Kim, K.W. Makkar, S.R. Crawford, J.D. Thalamuthu, A. Kochan, N.A. Leung, Y. Lo, J.W. Turana, Y. Castro-Costa, E. Larijani, B. Nabipour, I. Rockwood, K. Shifu, X. Lipton, R.B. Katz, M.J. Preux, P.-M. Guerchet, M. Lam, L. Ninimiya, T. Walker, R. Hendrie, H. Guaita, A. Chen, L.-K. Shahar, S. Dominguez, J. Krishna, M. Ganguli, M. Anstey, K.J. Crowe, M. Haan, M.N. Kumagai, S. Ng, T.P. Brodaty, H. Mayeux, R. Schupf, N. Petersen, R. Lipton, R. Lowe, E.S. Jorm, L.
Subjects: mental disorders
Abstract: Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries over 3 continents, including 14,792 women aged 60 years or older. We investigated the association between parity and the risk of dementia using logistic regression models that adjusted for age, educational level, hypertension, diabetes mellitus, and cohort, with additional analyses by region and dementia subtype. Results: Across all cohorts, grand multiparous (5 or more childbirths) women had a 47% greater risk of dementia than primiparous (1 childbirth) women (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.10-1.94), while nulliparous (no childbirth) women and women with 2 to 4 childbirths showed a comparable dementia risk to primiparous women. However, there were differences associated with region and dementia subtype. Compared to women with 1 to 4 childbirths, grand multiparous women showed a higher risk of dementia in Europe (OR = 2.99, 95% CI = 1.38-6.47) and Latin America (OR = 1.49, 95% CI = 1.04-2.12), while nulliparous women showed a higher dementia risk in Asia (OR = 2.15, 95% CI = 1.33-3.47). Grand multiparity was associated with 6.9-fold higher risk of vascular dementia in Europe (OR = 6.86, 95% CI = 1.81-26.08), whereas nulliparity was associated with a higher risk of Alzheimer disease (OR = 1.91, 95% CI 1.07-3.39) and non-Alzheimer non-vascular dementia (OR = 3.47, 95% CI = 1.44-8.35) in Asia. Conclusion: Parity is associated with women's risk of dementia, though this is not uniform across regions and dementia subtypes. © 2020 The Author(s).
Published: 2020

24. Parity and the risk of incident dementia: a COSMIC study

Author: Bae, J.B., Lipnicki, D.M., Han, J.W., Sachdev, P.S., Kim, T.H., Kwak, K.P., Kim, B.J., Kim, S.G., Kim, J.L., Moon, S.W., Park, J.H., Ryu, S.H., Youn, J.C., Lee, D.Y., Lee, D.W., Lee, S.B., Lee, J.J., Jhoo, J.H., Skoog, I., Najar, J., Sterner, T.R., Scarmeas, N., Yannakoulia, M., Dardiotis, E., Riedel-Heller, S., Roehr, S., Pabst, A., Ding, D., Zhao, Q., Liang, X., Lobo, A., De-la-Cámara, C., Lobo, E., Kim, K.W., and for, Cohort, Studies, of, Memory, in, an, International, Consortium, (COSMIC)
Abstract: AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Published: 2020

25. Parity and the risk of incident dementia: a COSMIC study

Author: Bae, J.B. Lipnicki, D.M. Han, J.W. Sachdev, P.S. Kim, T.H. Kwak, K.P. Kim, B.J. Kim, S.G. Kim, J.L. Moon, S.W. Park, J.H. Ryu, S.-H. Youn, J.C. Lee, D.Y. Lee, D.W. Lee, S.B. Lee, J.J. Jhoo, J.H. Skoog, I. Najar, J. Sterner, T.R. Scarmeas, N. Yannakoulia, M. Dardiotis, E. Riedel-Heller, S. Roehr, S. Pabst, A. Ding, D. Zhao, Q. Liang, X. Lobo, A. De-la-Cámara, C. Lobo, E. Kim, K.W. for Cohort Studies of Memory in an International Consortium (COSMIC)
Abstract: AIMS: To investigate the association between parity and the risk of incident dementia in women. METHODS: We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)). RESULTS: Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02-1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1-4 parities (HR = 1.30, 95% CI = 1.02-1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02-1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00-2.55), but the risk of AD was not significantly associated with parity. CONCLUSIONS: Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Published: 2020

26. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Author: Hofer, E., Roshchupkin, G.V., Adams, H.H.H., Knol, M.J., Lin, H., Li, S., Zare, H., Ahmad, S., Armstrong, N.J., Satizabal, C.L., Bernard, M., Bis, J.C., Gillespie, N.A., Luciano, M., Mishra, A., Scholz, M., Teumer, A., Xia, R., Jian, X., Mosley, T.H., Saba, Y., Pirpamer, L., Seiler, S., Becker, J.T., Carmichael, O., Rotter, J.I., Psaty, B.M., Lopez, O.L., Amin, N., van der Lee, S.J., Yang, Q., Himali, J.J., Maillard, P., Beiser, A.S., DeCarli, C., Karama, S., Lewis, L., Harris, M., Bastin, M.E., Deary, I.J., Veronica Witte, A., Beyer, F., Loeffler, M., Mather, K.A., Schofield, P.R., Thalamuthu, A., Kwok, J.B., Wright, M.J., Ames, D., Trollor, J., Jiang, J., Brodaty, H., Wen, W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., Niessen, W.J., Wittfeld, K., Bülow, R., Völker, U., Pausova, Z., Bruce Pike, G., Maingault, S., Crivello, F., Tzourio, C., Amouyel, P., Mazoyer, B., Neale, M.C., Franz, C.E., Lyons, M.J., Panizzon, M.S., Andreassen, O.A., Dale, A.M., Logue, M.A., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Stein, J.L., Thompson, P.M., Medland, S.E., Sachdev, P.S., Kremen, W.S., Wardlaw, J.M., Villringer, A., van Duijn, C.M., Grabe, H.J., Longstreth, W.T., Fornage, M., Paus, T., Debette, S., Arfan Ikram, M., Schmidt, H., Schmidt, R., Seshadri, S., Hofer, E., Roshchupkin, G.V., Adams, H.H.H., Knol, M.J., Lin, H., Li, S., Zare, H., Ahmad, S., Armstrong, N.J., Satizabal, C.L., Bernard, M., Bis, J.C., Gillespie, N.A., Luciano, M., Mishra, A., Scholz, M., Teumer, A., Xia, R., Jian, X., Mosley, T.H., Saba, Y., Pirpamer, L., Seiler, S., Becker, J.T., Carmichael, O., Rotter, J.I., Psaty, B.M., Lopez, O.L., Amin, N., van der Lee, S.J., Yang, Q., Himali, J.J., Maillard, P., Beiser, A.S., DeCarli, C., Karama, S., Lewis, L., Harris, M., Bastin, M.E., Deary, I.J., Veronica Witte, A., Beyer, F., Loeffler, M., Mather, K.A., Schofield, P.R., Thalamuthu, A., Kwok, J.B., Wright, M.J., Ames, D., Trollor, J., Jiang, J., Brodaty, H., Wen, W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., Niessen, W.J., Wittfeld, K., Bülow, R., Völker, U., Pausova, Z., Bruce Pike, G., Maingault, S., Crivello, F., Tzourio, C., Amouyel, P., Mazoyer, B., Neale, M.C., Franz, C.E., Lyons, M.J., Panizzon, M.S., Andreassen, O.A., Dale, A.M., Logue, M.A., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Stein, J.L., Thompson, P.M., Medland, S.E., Sachdev, P.S., Kremen, W.S., Wardlaw, J.M., Villringer, A., van Duijn, C.M., Grabe, H.J., Longstreth, W.T., Fornage, M., Paus, T., Debette, S., Arfan Ikram, M., Schmidt, H., Schmidt, R., and Seshadri, S.
Abstract: Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
Published: 2020

27. Investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis

Author: Peters, R, Yasar, S., Anderson, C.S, Andrews, S., Antikainen, R., Arima, H., Beckett, N., Beer, J.C., Bertens, A.S., Booth, A., Boxtel, M. van, Brayne, C., Brodaty, H., Carlson, M.C., Chalmers, J., Corrada, M., DeKosky, S., Derby, C., Dixon, R.A., Forette, F., Ganguli, M., Gool, W.A. van, Guaita, A., Hever, A.M., Hogan, D.B., Jagger, C., Katz, M., Kawas, C., Kehoe, P.G., Keinanen-Kiukaanniemi, S., Kenny, R.A., Kohler, S., Kunutsor, S.K., Laukkanen, J., Maxwell, C., McFall, G.P., Middelaar, T. van, Charante, E.P.M. van, Ng, T.P., Peters, Jean, Rawtaer, I., Richard, E., Rockwood, K., Ryden, L., Sachdev, P.S., Skoog, I., Skoog, J., Staessen, J.A., Stephan, B.C., Sebert, S., Thijs, L., Trompet, S., Tully, P.J., Tzourio, C., Vaccaro, R., Vaaramo, E., Walsh, E., Warwick, J., Anstey, K.J., Peters, R, Yasar, S., Anderson, C.S, Andrews, S., Antikainen, R., Arima, H., Beckett, N., Beer, J.C., Bertens, A.S., Booth, A., Boxtel, M. van, Brayne, C., Brodaty, H., Carlson, M.C., Chalmers, J., Corrada, M., DeKosky, S., Derby, C., Dixon, R.A., Forette, F., Ganguli, M., Gool, W.A. van, Guaita, A., Hever, A.M., Hogan, D.B., Jagger, C., Katz, M., Kawas, C., Kehoe, P.G., Keinanen-Kiukaanniemi, S., Kenny, R.A., Kohler, S., Kunutsor, S.K., Laukkanen, J., Maxwell, C., McFall, G.P., Middelaar, T. van, Charante, E.P.M. van, Ng, T.P., Peters, Jean, Rawtaer, I., Richard, E., Rockwood, K., Ryden, L., Sachdev, P.S., Skoog, I., Skoog, J., Staessen, J.A., Stephan, B.C., Sebert, S., Thijs, L., Trompet, S., Tully, P.J., Tzourio, C., Vaccaro, R., Vaaramo, E., Walsh, E., Warwick, J., and Anstey, K.J.
Abstract: Item does not contain fulltext, OBJECTIVE: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data. METHODS: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data. RESULTS: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those
Published: 2020

28. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Author: Dima, D. (Danai), Modabbernia, A. (Amirhossein), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L., Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), van't Ent, D. (Dennis), Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Williams, S.C.R. (Steven C. R.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), Frangou, S. (Sophia), Dima, D. (Danai), Modabbernia, A. (Amirhossein), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L., Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), van't Ent, D. (Dennis), Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Williams, S.C.R. (Steven C. R.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), and Frangou, S. (Sophia)
Abstract: Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
Published: 2020
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29. Cerebral small vessel disease genomics and its implications across the lifespan

Author: Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. (Quentin), Duperron, M.-G. (Marie-Gabrielle), Smith, A.V. (Albert), Knopman, D.S. (David), Schreiner, P.J. (Pamela), Evans, D.A. (Denis A.), Rotter, J.I. (Jerome I.), Beiser, A. (Alexa), Maniega, S.M. (Susana Muñoz), Beekman, M. (Marian), Trollor, J., Stott, D.J. (David. J.), Vernooij, M.W. (Meike), Wittfeld, K. (Katharina), Niessen, W.J. (Wiro), Soumaré, A. (Aicha), Boerwinkle, E.A. (Eric), Sidney, S. (Stephen), Turner, S.T. (Stephen), Davies, G. (Gail), Thalamuthu, A. (Anbupalam), Völker, U. (Uwe), Buchem, M.A. (Mark) van, Bryan, R.N. (R. Nick), Amin, N. (Najaf), Bastin, M.E. (Mark), Ames, D.J. (David), Teumer, A. (Alexander), Amouyel, P. (Philippe), Kwok, J.B. (John B.), Bülow, R. (Robin), Deary, I.J. (Ian), Schofield, P.R. (Peter R.), Brodaty, H. (Henry), Jiang, J. (Jiyang), Tabara, Y. (Yasuharu), Setoh, K. (Kazuya), Miyamoto, S. (Susumu), Yoshida, K. (Kazumichi), Nagata, M. (Manabu), Kamatani, Y. (Yoichiro), Matsuda, F. (Fumihiko), Psaty, B.M. (Bruce), Bennett, D.A. (David), De Jager, P., Mosley, T.H. (Thomas H.), Sachdev, P.S. (Perminder), Schmidt, R. (Reinhold), Warren, H. (Helen), Evangelou, E. (Evangelos), Trégouët, D.-A. (David-Alexandre), Andrade, M. (Mariza) de, Basu, S. (Saonli), Berr, C. (Claudine), Brody, J.A. (Jennifer A.), Chasman, D.I. (Daniel I.), Dartigues, J.-F., Folsom, A.R. (Aaron), Germain, M. (Marine), de Haan, H. (Hugoline), Heit, J.A. (John), Houwing-Duitermaat, J. (Jeanine), Kabrhel, C. (Christopher), Kraft, P. (Peter), Legal, G. (Grégoire), Lindström, S. (Sara), Monajemi, R. (Ramin), Morange, P.-E. (P.), Psaty, B.M. (Bruce M.), Reitsma, P.H. (Pieter H.), Jarvelin, M.-R. (Marjo-Riitta), Rose, L.M. (Lynda M.), Peyvandi, F. (Flora), Saut, N. (Noemie), Slagboom, E. (Eline), Smadja, D. (David), Smith, N.L. (Nicholas L.), Suchon, P. (Pierre), Tang, W. (Weihong), Taylor, K.D. (Kent D.), Tregouet, D.-A. (David-Alexandre), Tzourio, C. (Christophe), Visser, M.C.H. (Marieke) de, Hylckama Vlieg, A. (Astrid) van, Weng, L.-C., Wiggins, K.L. (Kerri L.), Gormley, A.M., Anttila, V. (Verneri), Winsvold, B.S. (Bendik S.), Palta, P. (Priit), Esko, T. (Tõnu), Pers, T.H. (Tune H.), 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 M.), Todt, U. (Unda), Freilinger, T.M. (Tobias M.), Ran, C. (Caroline), Gordon, S.G. (Scott G.), Stam, A.H. (Anine), Steinberg, S. (Stacy), Borck, G. (Guntram), 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), Schürks, M. (Markus), Ridker, P.M. (Paul M.), Gudlaug Hrafnsdottir, M. (Maria), Stefansson, H. (Hreinn), Ring, S.M. (Susan M.), Hottenga, J.J. (Jouke Jan), Penninx, B.W.J.H. (Brenda), Färkkilä, M. (Markus), Artto, V. (Ville), Kaunisto, M.A. (Mari), Vepsäläinen, S. (Salli), Malik, R. (Rainer), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela A. F.), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Kurki, M. (Mitja), Kals, M. (Mart), Mägi, R. (Reedik), Pärn, K. (Kalle), Hämäläinen, E. (Eija), Huang, H. (Hailiang), Byrnes, A.E. (Andrea E.), Franke, L. (Lude), Huang, J. (Jie), Stergiakouli, E. (Evie), Lee, P.H. (Phil H.), 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), Francke Christensen, A. (Anne), Folkmann Hansen, T. (Thomas), Werge, T. (Thomas), Kaprio, J. (Jaakko), Aromaa, A. (Arpo), Raitakari, O. (Olli), Ikram, M.A. (M. Arfan), Spector, T.D. (Timothy), Järvelin, M.-R. (Marjo-Riitta), Metspalu, A. (Andres), Kubisch, C. (Christian), Beckmann, J.S. (Jacques), Ferrari, M.D. (Michel), Belin, A.C. (Andrea C.), Wessman, M. (Maija), van den Maagdenberg, A.M.J.M. (Arn M. J. M.), Zwart, J-A. (John-Anker), Boomsma, D.I. (Dorret), Davey Smith, G. (George), 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), Ikram, M.A. (Arfan), Wen, W. (Wei), DeCarli, C. (Charles), Srikanth, V. (Velandai), Jukema, J.W. (Jan Wouter), Slagboom, P.E. (Eline), Kardia, S.L.R. (Sharon), Okada, Y. (Yukinori), Mazoyer, B. (Bernard), Wardlaw, J.M. (J.), Nyquist, P. (Paul), Mather, R., Grabe, H.J. (Hans Jörgen), Schmidt, H. (Helena), Van Duijn, C.M. (Cornelia M.), Gudnason, V. (Vilmundur), Longstreth Jr, W.T., Launer, L.J. (Lenore), Lathrop, M. (Mark), Seshadri, S. (Sudha), Adams, H.H.H. (Hieab), Matthews, P.M. (P.), Fornage, M. (Myriam), Debette, S. (Stéphanie), Sargurupremraj, M. (Muralidharan), Suzuki, H. (Hideaki), Jian, X. (Xueqiu), Sarnowski, C., Evans, T.E (Tavia), Bis, J.C. (Joshua), Eiriksdottir, G. (Gudny), Sakaue, S. (Saori), Terzikhan, N. (Natalie), Habes, M. (Mohamad), Zhao, W. (Wei), Armstrong, N.J. (Nicola J.), Hofer, E. (Edith), Yanek, L.R. (Lisa), Hagenaars, S.P. (Saskia P.), Kumar, R.B. (Rajan B.), Akker, E.B. (Erik) van den, McWhirter, R.E. (Rebekah E.), Trompet, S. (Stella), Mishra, A. (Aniket), Saba, Y. (Yasaman), Satizabal, C.L. (Claudia), Beaudet, G. (Gregory), Petit, L. (Laurent), Tsuchida, A. (Ami), Zago, L. (Laure), Schilling, S. (Sabrina), Sigurdsson, S. (Stefan), Gottesman, R.F. (Rebecca), Lewis, C.E. (Cora E.), Aggarwal, N.T. (Neelum T.), Lopez, O.L. (Oscar), Smith, J.A. (Jennifer A), Valdés Hernández, M.C. (Maria C.), van der Grond, J. (Jeroen), Wright, M.J. (Margaret), Knol, M.J. (Maria J.), Dörr, M. (Marcus), Thomson, R. (Russell), Bordes, C. (Constance), Le Grand, Q. 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(P.), Fornage, M. (Myriam), and Debette, S. (Stéphanie)
Abstract: White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
Published: 2020
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30. Five insights from the Global Burden of Disease Study 2019

Author: Murray, C.J.L., Abbafati, C., Abbas, K.M., Abbasi, M., Abbasi-Kangevari, M., Abd-Allah, F., Abdollahi, M., Abedi, P., Abedi, A., Abolhassani, H., Aboyans, V., Abreu, L.G., Abrigo, M.R.M., Abu-Gharbieh, E., Abu Haimed, A.K., Abushouk, A.I., Acebedo, A., Ackerman, I.N., Adabi, M., Adamu, A.A., Adebayo, O.M., Adelson, J.D., Adetokunboh, O.O., Afarideh, M., Afshin, A., Agarwal, G., Agrawal, A., Ahmad, T., Ahmadi, K., Ahmadi, M., Ahmed, M.B., Aji, B., Akinyemiju, T., Akombi, B., Alahdab, F., Alam, K., Alanezi, F.M., Alanzi, T.M., Albertson, S.B., Alemu, B.W., Alemu, Y.M., Alhabib, K.F., Ali, M., Ali, S., Alicandro, G., Alipour, V., Alizade, H., Aljunid, S.M., Alla, F., Allebeck, P., Almadi, M.A.H., Almasi-Hashiani, A., Al-Mekhlafi, H.M., Almulhim, A.M., Alonso, J., Al-Raddadi, R.M., Altirkawi, K.A., Alvis-Guzman, N., Amare, B., Amare, A.T, Amini, S., Amit, A.M.L., Amugsi, D.A., Anbesu, E.W., Ancuceanu, R., Anderlini, D., Anderson, J.A., Andrei, T., Andrei, C.L., Anjomshoa, M., Ansari, F., Ansari-Moghaddam, A., Antonio, C.A.T., Antony, C.M., Anvari, D., Appiah, S.C.Y., Arabloo, J., Arab-Zozani, M., Aravkin, A.Y., Arba, A.A.K., Aripov, T., Ärnlöv, J., Arowosegbe, O.O., Asaad, M., Asadi-Aliabadi, M., Asadi-Pooya, A.A., Ashbaugh, C., Assmus, M., Atout, M.M.W., Ausloos, M., Ausloos, F., Ayala Quintanilla, B.P., Ayano, G., Ayanore, M.A., Azari, S., Azene, Z.N., Babaee, E., Badawi, A., Badiye, A.D., Bagherzadeh, M., Bairwa, M., Bakhtiari, A., Bakkannavar, S.M., Balachandran, A., Banach, M., Banerjee, S.K., Banik, P.C., Baraki, A.G., Barker-Collo, S.L., Basaleem, H., Basu, S., Baune, B.T., Bayati, M., Baye, B.A., Bedi, N., Beghi, E., Bell, M.L., Bensenor, I.M., Berhe, K., Berman, A.E., Bhagavathula, A.S., Bhala, N., Bhardwaj, P., Bhattacharyya, K., Bhattarai, S., Bhutta, Z.A., Bijani, A., Bikbov, B., Biondi, A., Bisignano, C., Biswas, R.K., Bjørge, T., Bohlouli, S., Bohluli, M., Bolla, S.R.R., Boloor, A., Bose, D., Boufous, S., Brady, O.J., Braithwaite, D., Brauer, M., Breitborde, N.J.K, Brenner, H., Breusov, A.V., Briant, P.S., Briggs, A.M., Britton, G.B., Brugha, T., Burugina Nagaraja, S., Busse, R., Butt, Z.A., Caetano dos Santos, F.L., Cámera, L.L.A., Campos-Nonato, I.R., Campuzano Rincon, J.C., Car, J., Cárdenas, R., Carreras, G., Carrero, J. 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Steiner, C., Stokes, M.A., Stranges, S., Suchdev, P.S., Sudaryanto, A., Sufiyan, M.B., Suliankatchi Abdulkader, R., Sulo, G., Swope, C.B., Sylte, D.O., Tabarés-Seisdedos, R., Tabuchi, T., Tadakamadla, S.K., Taddele, B.W., Taherkhani, A., Tahir, Z., Tamiru, A.T., Tang, M., Tareque, M.I., Tefera, Y.G.G., Tela, F.G.G., Temsah, M-H, Terrason, S., Thakur, B., Thankappan, K.R., Thapar, R., Thomas, N., Titova, M.V., Tlou, B., Tonelli, M., Topor-Madry, R., Torre, A.E., Touvier, M., Tovani-Palone, M.R., Tran, B.X., Travillian, R., Uddin, R., Ullah, I., Unnikrishnan, B., Upadhyay, E., Vacante, M., Vaicekonyte, R., Valdez, P.R., Valli, A., Vasankari, T.J., Vasseghian, Y., Venketasubramanian, N., Vidale, S., Violante, F.S., Vlassov, V., Vollset, S.E., Vongpradith, A., Vu, G.T., W/hawariat, F.G., Waheed, Y., Wamai, R.G., Wang, F., Wang, H., Wang, J., Wang, Y., Wang, Y-P, Watson, A., Wei, J., Weintraub, R.G., Weiss, J., Welay, F.T., Werdecker, A., Westerman, R., Whiteford, H.A., Wiangkham, T., Wickramasinghe, N.D., Wilner, L.B., Wojtyniak, B., Wolfe, C.D.A., Wondmeneh, T.G., Wu, A-M, Wu, C., Wulf Hanson, S., Wunrow, H.Y., Xie, Y., Yahyazadeh Jabbari, S.H., Yamagishi, K., Yaya, S., Yazdi-Feyzabadi, V., Yearwood, J.A., Yeheyis, T.Y., Yeshitila, Y.Gi., Yip, P., Yonemoto, N., Yoon, S-J, Younis, M.Z., Younker, T.P., Yousefinezhadi, T., Yu, C., Yu, Y., Yuce, D., Yusefzadeh, H., Zaidi, S.S., Zaman, S.B., Zamanian, M., Zangeneh, A., Zarafshan, H., Zastrozhin, M.S., Zewdie, K.A., Zhang, Z-J, Zhang, J., Zhang, Y., Zhao, X-J.G., Zhao, Y., Zheleva, B., Zheng, P., Zhu, C., Ziapour, A., Zimsen, S.R.M., Lopez, A.D., Vos, T., and Lim, S.S.
Abstract: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3·5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.
Published: 2020

31. Genetic and environmental causes of variation in epigenetic aging across the lifespan

Author: Li, S., Nguyen, T.L., Wong, E.M., Dugué, P-A, Dite, G.S., Armstrong, N.J., Craig, J.M., Mather, K.A., Sachdev, P.S., Saffery, R., Sung, J., Tan, Q., Thalamuthu, A., Milne, R.L., Giles, G.G., Southey, M.C., Hopper, J.L., Li, S., Nguyen, T.L., Wong, E.M., Dugué, P-A, Dite, G.S., Armstrong, N.J., Craig, J.M., Mather, K.A., Sachdev, P.S., Saffery, R., Sung, J., Tan, Q., Thalamuthu, A., Milne, R.L., Giles, G.G., Southey, M.C., and Hopper, J.L.
Abstract: Background DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan. Results In order to investigate the genetic and environmental causes of DNAm age variation across the lifespan, we pooled genome-wide DNA methylation data for 4217 people aged 0–92 years from 1871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent–offspring, and spouse pairs by cohabitation status. Genetic and environmental variance components models were fitted and compared. We found that twin pair correlations were − 0.12 to 0.18 around birth, not different from zero (all P > 0.29). For all pairs of relatives, their correlations increased with time spent living together (all P < 0.02) at different rates (MZ > DZ and siblings > parent–offspring; P < 0.001) and decreased with time spent living apart (P = 0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI] 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI 1.13 to 9.47) times greater than for parent–offspring pairs. Genetic factors explained 13% (95% CI − 10 to 35%) of variation (P = 0.27). Similar results were found for another two epigenetic clocks, suggesting that our observations are robust to how DNAm age is measured. In addition, results for the other clocks were consistent with there also being a role for prenatal environmental factors in determining their variation. Conclusions Variation in DNAm age is mostly caused by environmental factors, including those share
Published: 2020

32. Genome-wide Meta-analysis finds the ACSL5-ZDHHC6 locus Is associated with ALS and links weight loss to the disease genetics

Author: Iacoangeli, A., Lin, T., Al Khleifat, A., Jones, A.R., Opie-Martin, S., Coleman, J.R.I., Shatunov, A., Sproviero, W., Williams, K.L., Garton, F., Restuadi, R., Henders, A.K., Mather, K.A., Needham, M., Mathers, S., Nicholson, G., Rowe, D.B., Henderson, R., McCombe, P.A., Pamphlett, R., Blair, I.P., Schultz, D., Sachdev, P.S., Newhouse, S.J., Proitsi, P., Fogh, I., Ngo, S.T., Dobson, R.J.B., Wray, N.R., Steyn, F.J., Al-Chalabi, A., Iacoangeli, A., Lin, T., Al Khleifat, A., Jones, A.R., Opie-Martin, S., Coleman, J.R.I., Shatunov, A., Sproviero, W., Williams, K.L., Garton, F., Restuadi, R., Henders, A.K., Mather, K.A., Needham, M., Mathers, S., Nicholson, G., Rowe, D.B., Henderson, R., McCombe, P.A., Pamphlett, R., Blair, I.P., Schultz, D., Sachdev, P.S., Newhouse, S.J., Proitsi, P., Fogh, I., Ngo, S.T., Dobson, R.J.B., Wray, N.R., Steyn, F.J., and Al-Chalabi, A.
Abstract: We meta-analyze amyotrophic lateral sclerosis (ALS) genome-wide association study (GWAS) data of European and Chinese populations (84,694 individuals). We find an additional significant association between rs58854276 spanning ACSL5-ZDHHC6 with ALS (p = 8.3 × 10−9), with replication in an independent Australian cohort (1,502 individuals; p = 0.037). Moreover, B4GALNT1, G2E3-SCFD1, and TRIP11-ATXN3 are identified using a gene-based analysis. ACSL5 has been associated with rapid weight loss, as has another ALS-associated gene, GPX3. Weight loss is frequent in ALS patients and is associated with shorter survival. We investigate the effect of the ACSL5 and GPX3 single-nucleotide polymorphisms (SNPs), using longitudinal body composition and weight data of 77 patients and 77 controls. In patients’ fat-free mass, although not significant, we observe an effect in the expected direction (rs58854276: −2.1 ± 1.3 kg/A allele, p = 0.053; rs3828599: −1.0 ± 1.3 kg/A allele, p = 0.22). No effect was observed in controls. Our findings support the increasing interest in lipid metabolism in ALS and link the disease genetics to weight loss in patients.
Published: 2020

33. Five insights from the Global Burden of Disease Study 2019.

Author: Hamadeh R.R., Soyiri I.N., Sreeramareddy C.T., Srinivasan V., Sripada K., Stovner L.J., Stockfelt L., Sultan I., Swope C.B., Vaicekonyte R., Sykes B.L., Szumowski L., Tabb K.M., Tabuchi T., Taddele B.W., Tahir Z., Tareque M.I., Tarigan I.U., Taveira N., Thankappan K.R., Thomas N., Varughese S., Touvier M., Tran B.X., Tsatsakis A., Vardavas C., Ullah I., Umeokonkwo C.D., Undurraga E.A., Upadhyay E., Vasankari T.J., Vasconcelos A.N., Veisani Y., Vidale S., Waheed Y., Wei J., Wang F., Zhao X.G., Wang Y., Yu C., Zhang Z., Wang H., Weiss J., Wiangkham T., Wickramasinghe N.D., Wu A., Xie Y., Xu G., Yahyazadeh Jabbari S., Yilgwan C.S., Yonemoto N., Younis M.Z., Younker T.P., Yu Y., Zaidi S., Zhang J., Zhang Y., Zheleva B., Zhu C., Abbafati C., Machado D.B., Cislaghi B., Salman O.M., Karanikolos M., McKee M., Abbas K.M., Brady O.J., Larson H.J., Trias-Llimos S., Cummins S., Langan S.M., Sartorius B., Hafiz A., Jenabi E., Mohammad Gholi Mezerji N., Borzouei S., Azarian G., Khazaei S., Abbasi M., Asghari B., Masoumi S., Komaki H., Taherkhani A., Adabi M., Abbasifard M., Bazmandegan G., Kamiab Z., Vakilian A., Anjomshoa M., Mokari A., Sabour S., Shahbaz M., Saeedi R., Ahmadieh H., Yousefinezhadi T., Haj-Mirzaian A., Nikbakhsh R., Safi S., Asgari S., Irvani S.N., Jahanmehr N., Ramezanzadeh K., Abbasi-Kangevari M., Khayamzadeh M., Abbastabar H., Shirkoohi R., Fazlzadeh M., Janjani H., Hosseini M., Mansournia M., Tohidinik H., Bakhtiari A., Fazaeli A., Mousavi S., Hasanzadeh A., Nabavizadeh B., Malekzadeh R., Hashemian M., Pourshams A., Salimzadeh H., Sepanlou S.G., Afarideh M., Esteghamati A., Esteghamati S., Ghajar A., Heidari B., Rezaei N., Mohamadi E., Rahimi-Movaghar A., Rahim F., Eskandarieh S., Sahraian M., Mohebi F., Aminorroaya A., Ebrahimi H., Farzadfar F., Mohajer B., Pishgar F., Saeedi Moghaddam S., Shabani M., Zarafshan H., Abolhassani H., Hafezi-Nejad N., Heidari-Soureshjani R., Abdollahi M., Farahmand M., Salamati P., Mehrabi Nasab E., Tajdini M., Aghamir S., Mirzaei R., Dibaji Forooshani Z., Khater M.M., Abd-Allah F., Abdelalim A., Abualhasan A., El-Jaafary S.I., Hassan A., Elsharkawy A., Khater A.M., Elhabashy H.R., Salem M.R.R., Salem H., Sadeghi M., Jafarinia M., Amini-Rarani M., Mohammadifard N., Sarrafzadegan N., Abdollahpour I., Sarveazad A., Tehrani-Banihashemi A., Yoosefi Lebni J., Manafi N., Pazoki Toroudi H., Dorostkar F., Alipour V., Sheikhtaheri A., Arabloo J., Azari S., Ghashghaee A., Rezapour A., Naserbakht M., Kabir A., Mehri F., Yousefifard M., Asadi-Aliabadi M., Babaee E., Eshrati B., Goharinezhad S., Moradi M., Abedi P., Rashedi V., Kumar V., Elgendy I.Y., Basu S., Park J., Pereira A., Norheim O.F., Eagan A.W., Cahill L.E., Sheikh A., Abushouk A.I., Thakur B., Barnighausen T.W., Shrime M.G., Abedi A., Doshi C.P., Abegaz K.H., Geberemariyam B.S., Aynalem Y.A., Shiferaw W.S., Abosetugn A.E., Aboyans V., Abrams E.M., Gitimoghaddam M., Kissoon N., Stubbs J.L., Brauer M., Iyamu I.O., Kopec J.A., Pourmalek F., Ribeiro A.P., Malta D.C., Gomez R.S., Abreu L.G., Abrigo M.R.M., Almulhim A.M., Dahlawi S.M.A., Pottoo F.H., Menezes R.G., Alanzi T.M., Alumran A.K., Abu Haimed A.K., Madadin M., Alanezi F.M., Abu-Gharbieh E., Saddik B., Abu-Raddad L.J., Samy A.M., El Nahas N., Shalash A.S., Nabhan A.F., Kamath A.M., Kassebaum N.J., Aravkin A.Y., Kochhar S., Sorensen R.J.D., Afshin A., Burkart K., Cromwell E.A., Gakidou E., Hay S.I., Kyu H.H., Lopez A.D., Lozano R., Misganaw A.T., Mokdad A.H., Naghavi M., Pigott D.M., Reiner Jr R.C., Roth G.A., Stanaway J.D., Vollset S., Vos T., Lim S.S., Murray C.J.L., Kalani R., Ikuta K.S., Cho D.Y., Kneib C.J., Crowe C.S., Massenburg B.B., Morrison S.D., Acebedo A., Adelson J.D., Agesa K.M., Alam T., Albertson S.B., Anderson J.A., Antony C.M., Ashbaugh C., Assmus M., Azhar G., Balassyano S., Bannick M.S., Barthelemy C.M., Bender R.G., Bennitt F.B., Bertolacci G.J., Biehl M.H., Bisignano C., Boon-Dooley A.S., Briant P.S., Bryazka D., Bumgarner B.R., Callender C.S., Cao J., Castle C.D., Castro E., Causey K., Cercy K.M., Chalek J., Cohen A.J., Comfort H., Compton K., Croneberger A.J., Cruz J.A., Cunningham M., Dangel W.J., Dean F.E., DeCleene N.K., Deen A., Degenhardt L., Dingels Z.V., Dippenaar I.N., Dirac M.A., Dolgert A.J., Emmons-Bell S., Estep K., Farag T., Feigin V.L., Feldman R., Ferrara G., Ferrari A.J., Fitzgerald R., Force L.M., Fox J.T., Frank T.D., Fu W., Fukutaki K., Fuller J.E., Fullman N., Galles N.C., Gardner W.M., Gershberg Hayoon A., Goren E., Gorman T.M., Gottlich H.C., Guo G., Haddock B., Hagins H., Haile L.M., Hamilton E.B., Han C., Han H., Harvey J.D., Henny K., Henrikson H.J., Henry N.J., Herbert M.E., Hsiao T., Huynh C.K., Iannucci V.C., Ippolito H., Irvine C.M.S., Jafari H., Jahagirdar D., James S.L., Johnson C.O., Johnson S.C., Keller C., Kemmer L., Kendrick P.J., Knight M., Kocarnik J.M., Krohn K.J., Larson S.L., Lau K.M., Ledesma J.R., Leever A.T., LeGrand K.E., Lescinsky H., Lin C., Liu H., Liu Z., Lo J., Lu A., Ma J., Maddison E.R., Manguerra H., Marks A., Martopullo I., Mastrogiacomo C.I., May E.A., Mooney M.D., Mosser J.F., Mullany E.C., Mumford J., Munro S.B., Nandakumar V., Nguyen J., Nguyen M., Nichols E., Nixon M.R., Odell C.M., Ong K.L., Orji A.U., Ostroff S.M., Pasovic M., Paulson K.R., Pease S.A., Pennini A., Pierce M., Pilz T.M., Pletcher M., Rao P.C., Razo C., Redford S.B., Reinig N., Reitsma M.B., Rhinehart P., Robalik T., Roberts N.L.S., Rolfe S., Sbarra A.N., Schaeffer L.E., Shackelford K.A., Shadid J., Sharara F., Shaw D.H., Sheena B.S., Simpson K.E., Smith A., Spencer C.N., Spurlock E.E., Stark B.A., Steiner C., Steuben K.M., Sylte D.O., Tang M., Taylor H.J., Terrason S., Thomson A.M., Torre A.E., Travillian R., Troeger C.E., Vongpradith A., Walters M.K., Wang J., Watson A., Watson S., Whisnant J.L., Whiteford H.A., Wiens K.E., Wilner L.B., Wilson S., Wool E.E., Wozniak S.S., Wu J., Wulf Hanson S., Wunrow H., Xu R., Yadgir S., Yearwood J.A., York H.W., Yuan C., Zhao J.T., Zheng P., Zimsen S.R.M., Zlavog B.S., Chang A.Y., Oren E., Buchbinder R., Chin K.L., Guo Y., Polkinghorne K.R., Thrift A.G., Ackerman I.N., Cicuttini F.M., Li S., Zaman S., Suleria H., Cowie B.C., Wijeratne T., Patton G.C., Sawyer S.M., Adair T., Meretoja A., Adetokunboh O.O., Adamu A.A., Iwu C.J., Parry C.D.H., Seedat S., Ndwandwe D.E., Mahasha P.W., Stein D.J., Nnaji C.A., Sambala E.Z., Wiysonge C.S., Adebayo O.M., Ilesanmi O.S., Owolabi M.O., Adeoye A.M., Adedeji I.A., Adekanmbi V., Ibitoye S.E., John-Akinola Y.O., Oluwasanu M.M., Oghenetega O.B., Akinyemi R.O., Zandian H., Adham D., Zahirian Moghadam T., Advani S.M., Teagle W.L., Braithwaite D., Agasthi P., Saadatagah S., Afshari M., Agardh E.E., Allebeck P., Danielsson A., Deuba K., Carrero J.J., Fereshtehnejad S., Arnlov J., Nowak C., Cederroth C.R., Ahmadi A., Mills E.J., Kurmi O.P., Olagunju A.T., Agarwal G., Sathish T., Aghaali M., Mohammadbeigi A., Agrawal A., Ahmad T., Ahmadi K., Maleki S., Naderi M., Salahshoor M.R., Pourmirza Kalhori R., Almasi A., Salimi Y., Siabani S., Ziapour A., Barzegar A., Khazaie H., Kianipour N., Amiri F., Salehi Zahabi S., Mirzaei M., Shamsi M., Najafi F., Jalali A., Ghadiri K., Heydarpour F., Fattahi N., Karami Matin B., Kazemi Karyani A., Pirsaheb M., Rajati F., Sadeghi E., Safari Y., Sharafi K., Soltani S., Vasseghian Y., Atafar Z., Jalilian F., Mirzaei-Alavijeh M., Saeidi S., Soofi M., Zangeneh A., Mansouri B., Ahmadi M., Khafaie M.A., Safiri S., Moghadaszadeh M., Asghari Jafarabadi M., Doshmangir L., Jadidi-Niaragh F., Ghafourifard M., Spotin A., Khodayari M., Samadi Kafil H., Kalankesh L.R., Ahmadpour E., Yousefi B., Ansari F., Hassankhani H., Karimi S., Haririan H., Mereta S., Ahmed M.B., Feyissa G.T., Ciobanu L.G., Aji B., Aynalem G.L., Gebresillassie B., Tefera Y.G., Akalu T.Y., Baraki A.G., Tesema G.A., Tessema Z.T., Tamiru A.T., Azene Z.N., Netsere H.B., Yano Y., Akinyemiju T., Wu C., Zadey S., Samad Z., Ji J.S., Doshi P.P., John O., Jha V., Maulik P.K., Pesudovs K., Resnikoff S., Mitchell P.B., Sachdev P.S., Akombi B., Godinho M.A., Ivers R.Q., Peden A.E., Biswas R., Boufous S., Akunna C.J., Alahdab F., Hammer M.S., van Donkelaar A., Al-Aly Z., Dellavalle R.P., Alam S., Martin R.V., Alam N., De Leo D., Tadakamadla S.K., Alam K., Alcalde-Rabanal J.E., Avila-Burgos L., Servan-Mori E., Denova-Gutierrez E., Rodriguez-Ramirez S., Morales L., Poznanska A., Wojtyniak B., Rivera J.A., Campos-Nonato I.R., Campuzano Rincon J., Sanchez-Pimienta T.G., Mengesha M.B., Welay F.T., Alema N.M., Demsie D.G., Teame H., Teklehaimanot B.F., Alemu B.W., Gultie T., Bante A.B., Yeshitila Y.G., Geramo Y.C.D., Glagn M., Sorrie M.B., W/hawariat F.G., Amare A., Kasa A., Alemu Y., Mihretie K.M., Atnafu D.D., Demeke F.M., Melese A., Bante S.A., Dessie G.A., Mengesha E.W., Nigatu D., Almadi M.A.H., Alhabib K.F., Mohammad Y., Altirkawi K.A., Temsah M., Kugbey N., Ayanore M.A., Alhassan R.K., Ali M., Ali S., Alicandro G., Kalhor R., Alijanzadeh M., Alinia C., Yusefzadeh H., Didarloo A., Alizade H., 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Mantilla Herrera A.M., Santomauro D.F., Mirica A., Ausloos M., Herteliu C., Otoiu A., Pana A., Andrei T., Stefan S., Androudi S., Angus C., Ansari I., Pourjafar H., Shams-Beyranvand M., Ansari-Moghaddam A., Khammarnia M., Antonazzo I., Ferrara P., Conti S., Cortesi P.A., Fornari C., Lee P.H., Antriyandarti E., Yousefi Z., Rafiei A., Javidnia J., Faridnia R., Anvari D., Moosazadeh M., Rezai M., Daryani A., Fareed M., Anwer R., Appiah S., Paudel D., Dichgans M., Riahi S., Rajabpour-Sanati A., Arab-Zozani M., Arba A.A.K., Aremu O., Ariani F., Aripov T., Armoon B., Mahdavi M.M., Arowosegbe O.O., Tediosi F., Aryal K.K., Mosapour A., Yaminfirooz M., Arzani A., Bijani A., Jahani M.A., Mouodi S., Zamani M., Asaad M., Dianatinasab M., Bahrami M., Pakshir K., Asadi-Pooya A.A., Bayati M., Shahabi S., Athari S., Atout M.M.W., Atteraya M.S., Brugha T., Ausloos F., Avokpaho E.F.G., Room R., Islam M., Edvardsson D., Rahman M., Ayala Quintanilla B., Gething P.W., Briggs A.M., Ayano G., Hendrie D., 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Abstract: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Copyright © 2020 Elsevier Ltd
Published: 2020

34. Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.

Author: Shetty B.S.K., Stein C., Stokes M.A., Sufiyan M.B., Suleria H.A.R., Sultan I., Szumowski L., Tabares-Seisdedos R., Tabuchi T., Tadakamadla S.K., Taddele B.W., Tadesse D.B., Taherkhani A., Tamiru A.T., Tanser F.C., Tareque M.I., Tarigan I.U., Teagle W.L., Tediosi F., Tefera Y.G.G., Tela F.G., Tessema Z.T., Thakur B., Titova M.V., Tonelli M., Topor-Madry R., Topouzis F., Tovani-Palone M.R.R., Tran B.X., Travillian R., Troeger C.E., Tudor Car L., Uddin R., Ullah I., Umeokonkwo C.D., Unnikrishnan B., Upadhyay E., Uthman O.A., Vacante M., Valdez P.R., Varughese S., Vasankari T.J., Vasseghian Y., Venketasubramanian N., Violante F.S., Vlassov V., Vollset S.E., Vongpradith A., Vos T., Waheed Y., Walters M.K., Wamai R.G., Wang H., Wang Y.-P., Weintraub R.G., Weiss J., Werdecker A., Westerman R., Wilner L.B., Woldu G., Wolfe C.D.A., Wu A.-M., Wulf Hanson S., Xie Y., Yahyazadeh Jabbari S.H., Yamagishi K., Yano Y., Yaya S., Yazdi-Feyzabadi V., Yearwood J.A., Yeshitila Y.G., Yip P., Yonemoto N., Younis M.Z., Yousefi Z., Yousefinezhadi T., Yusefzadeh H., Zadey S., Zahirian Moghadam T., Zaidi S.S., Zaki L., Zaman S.B., Zamanian M., Zandian H., Zastrozhin M.S., Zewdie K.A., Zhang Y., Zhao X.-J.G., Zhao Y., Zheng P., Zhu C., Ziapour A., Zlavog B.S., Zodpey S., Murray C.J.L., Lozano R., Fullman N., Mumford J.E., Knight M., Barthelemy C.M., Abbafati C., Abbastabar H., Abd-Allah F., Abdollahi M., Abedi A., Abolhassani H., Abosetugn A.E., Abreu L.G., Abrigo M.R.M., Abu Haimed A.K., Abushouk A.I., Adabi M., Adebayo O.M., Adekanmbi V., Adelson J., Adetokunboh O.O., Adham D., Advani S.M., Afshin A., Agarwal G., Agasthi P., Aghamir S.M.K., Agrawal A., Ahmad T., Akinyemi R.O., Alahdab F., Al-Aly Z., Alam K., Albertson S.B., Alemu Y.M., Alhassan R.K., Ali M., Ali S., Alipour V., Aljunid S.M., Alla F., Almadi M.A.H., Almasi A., Almasi-Hashiani A., Almasri N.A., Al-Mekhlafi H.M., Almulhim A.M., Alonso J., Al-Raddadi R.M., Altirkawi K.A., Alvis-Guzman N., Alvis-Zakzuk N.J., Amini S., Amini-Rarani M., Amiri F., Amit A.M.L., Amugsi D.A., Ancuceanu R., Anderlini D., Andrei C.L., Androudi S., Ansari F., Ansari-Moghaddam A., Antonio C.A.T., Antony C.M., Antriyandarti E., Anvari D., Anwer R., Arabloo J., Arab-Zozani M., Aravkin A.Y., Aremu O., Arnlov J., Asaad M., Asadi-Aliabadi M., Asadi-Pooya A.A., Athari S.S., Atout M.M.W., Ausloos M., Avila-Burgos L., Ayala Quintanilla B.P., Ayano G., Ayanore M.A., Aynalem Y.A., Aynalem G.L., Ayza M.A., Azari S., Azzopardi P.S., B D.B., Babaee E., Badiye A.D., Bahrami M.A., Baig A.A., Bakhshaei M.H., Bakhtiari A., Bakkannavar S.M., Balachandran A., Banach M., Banerjee S.K., Banik P.C., Bante A.B., Bante S.A., Barker-Collo S.L., Barnighausen T.W., Barrero L.H., Bassat Q., Basu S., Baune B.T., Bayati M., Baye B.A., Bedi N., Beghi E., Behzadifar M., Bekuma T.T.T., Bell M.L., Bensenor I.M., Berman A.E., Bernabe E., Bernstein R.S., Bhagavathula A.S., Bhandari D., Bhardwaj P., Bhat A.G., Bhattacharyya K., Bhattarai S., Bhutta Z.A., Bijani A., Bikbov B., Bilano V., Biondi A., Birihane B.M., Bockarie M.J., Bohlouli S., Bojia H.A., Bolla S.R.R., Boloor A., Brady O.J., Braithwaite D., Briggs A.M., Briko N.I., Burugina Nagaraja S., Busse R., Butt Z.A., Caetano dos Santos F.L., Cahuana-Hurtado L., Camera L.A., Cardenas R., Carreras G., Carrero J.J., Carvalho F., Castaldelli-Maia J.M., Castaneda-Orjuela C.A., Castelpietra G., Castro F., Catala-Lopez F., Cederroth C.R., Cerin E., Chandan J.S., Chang A.Y., Charan J., Chattu V.K., Chaturvedi S., Chin K.L., Cho D.Y., Choi J.-Y.J., Christensen H., Chu D.-T., Chung M.T., Ciobanu L.G., Cirillo M., Compton K., Cortesi P.A., Costa V.M., Cousin E., Dahlawi S.M.A., Damiani G., Dandona L., Dandona R., Darega Gela J., Darwesh A.M., Daryani A., Dash A.P., Davey G., Davila-Cervantes C.A., Davletov K., De Neve J.-W., Denova-Gutierrez E., Deribe K., Dervenis N., Desai R., Dharmaratne S.D., Dhungana G.P., Dianatinasab M., Dias da Silva D., Diaz D., Dippenaar I.N., Do H.T., Dorostkar F., 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Hafezi-Nejad N., Hafiz A., Haile T.G., Hamadeh R.R., Hameed S., Hamidi S., Han C., Han H., Handiso D.W., Hanif A., Hankey G.J., Haro J.M., Hasaballah A.I., Hasan M.M., Hashi A., Hassan S., Hassan A., Hassanipour S., Hassankhani H., Havmoeller R.J., Hay S.I., Hayat K., Heidari G., Heidari-Soureshjani R., Hendrie D., Herteliu C., Hird T.R., Ho H.C., Hole M.K., Holla R., Hoogar P., Hopf K.P., Horita N., Hossain N., Hosseini M., Hosseinzadeh M., Hostiuc M., Hostiuc S., Househ M., Hsieh V.C.-R., Hu G., Huda T.M., Humayun A., Hwang B.-F., Iavicoli I., Ibitoye S.E., Ikeda N., Ilesanmi O.S., Ilic M.D., Inbaraj L.R., Iqbal U., Irvani S.S.N., Irvine C.M.S., Islam M.M., Islam S.M.S., Islami F., Iso H., Iwu C.J., Jaafari J., Jadidi-Niaragh F., Jafarinia M., Jahagirdar D., Jahani M.A., Jahanmehr N., Jakovljevic M., Janjani H., Javaheri T., Jayatilleke A.U., Jenabi E., Jha R.P., Jha V., Ji J.S., Jia P., John-Akinola Y.O., Jonas J.B., Joukar F., Jozwiak J.J., Jurisson M., Kabir Z., Kalankesh L.R., Kalhor R., Kamath A.M., Kanchan T., Kapoor N., Karami Matin B., Karanikolos M., Karimi S.M., Kassebaum N.J., Katikireddi S.V., Kayode G.A., Keiyoro P.N., Khader Y.S., Khammarnia M., Khan M., Khan E.A., Khang Y.-H., Khatab K., Khater A.M., Khater M.M., Khatib M.N., Khayamzadeh M., Khubchandani J., Kianipour N., Kim Y.J., Kimokoti R.W., Kinfu Y., Kisa A., Kissimova-Skarbek K., Kivimaki M., Kneib C.J., Kocarnik J.M., Kochhar S., Kohler S., Kopec J.A., Korotkova A.V., Korshunov V.A., Kosen S., Kotlo A., Koul P.A., Koyanagi A., Krishan K., Krohn K.J., Kugbey N., Kulkarni V., Kumar G.A., Kumar N., Kumar M., Kurmi O.P., Kusuma D., Kyu H.H., La Vecchia C., Lacey B., Lal D.K., Lalloo R., Landires I., Lansingh V.C., Larsson A.O., Lasrado S., Lau K.M.-M., Lauriola P., Lazarus J.V., Ledesma J.R., Lee P.H., Lee S.W.H., Leever A.T., LeGrand K.E., Leigh J., Leonardi M., Li S., Lim S.S., Lim L.-L., Liu X., Logroscino G., Lopez A.D., Lopukhov P.D., Lotufo P.A., Lu A., Ma J., Madadin M., Mahasha P.W., Mahmoudi M., Majeed A., Malagon-Rojas J.N., Maleki S., Malta D.C., Mansouri B., Mansournia M.A., Martini S., Martins-Melo F.R., Martopullo I., Massenburg B.B., Mastrogiacomo C.I., Mathur M.R., McAlinden C., McKee M., Medina-Solis C.E., Meharie B.G., Mehndiratta M.M., Mehrabi Nasab E., Mehri F., Mehrotra R., Mekonnen T., Melese A., Memiah P.T.N., Mendoza W., Menezes R.G., Mensah G.A., Meretoja T.J., Meretoja A., Mestrovic T., Miazgowski B., Michalek I.M., Mirrakhimov E.M., Mirzaei M., Mirzaei-Alavijeh M., Mitchell P.B., Moazen B., Moghadaszadeh M., Mohamadi E., Mohammad Y., Mohammad D.K., Mohammad Gholi Mezerji N., Mohammadian-Hafshejani A., Mohammed S., Mohammed J.A., Mokdad A.H., Monasta L., Mondello S., Moradi M., Moradi-Lakeh M., Moradzadeh R., Moraga P., Morgado-da-Costa J., Morrison S.D., Mosapour A., Mosser J.F., Mousavi Khaneghah A., Muriithi M.K., Mustafa G., Nabhan A.F., Naderi M., Nagarajan A.J., Naghavi M., Naghshtabrizi B., Naimzada M.D., Nangia V., Nansseu J.R., Nayak 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P.R., Varughese S., Vasankari T.J., Vasseghian Y., Venketasubramanian N., Violante F.S., Vlassov V., Vollset S.E., Vongpradith A., Vos T., Waheed Y., Walters M.K., Wamai R.G., Wang H., Wang Y.-P., Weintraub R.G., Weiss J., Werdecker A., Westerman R., Wilner L.B., Woldu G., Wolfe C.D.A., Wu A.-M., Wulf Hanson S., Xie Y., Yahyazadeh Jabbari S.H., Yamagishi K., Yano Y., Yaya S., Yazdi-Feyzabadi V., Yearwood J.A., Yeshitila Y.G., Yip P., Yonemoto N., Younis M.Z., Yousefi Z., Yousefinezhadi T., Yusefzadeh H., Zadey S., Zahirian Moghadam T., Zaidi S.S., Zaki L., Zaman S.B., Zamanian M., Zandian H., Zastrozhin M.S., Zewdie K.A., Zhang Y., Zhao X.-J.G., Zhao Y., Zheng P., Zhu C., Ziapour A., Zlavog B.S., Zodpey S., Murray C.J.L., Lozano R., Fullman N., Mumford J.E., Knight M., Barthelemy C.M., Abbafati C., Abbastabar H., Abd-Allah F., Abdollahi M., Abedi A., Abolhassani H., Abosetugn A.E., Abreu L.G., Abrigo M.R.M., Abu Haimed A.K., Abushouk A.I., Adabi M., Adebayo O.M., Adekanmbi V., Adelson J., Adetokunboh O.O., Adham D., Advani S.M., Afshin A., Agarwal G., Agasthi P., Aghamir S.M.K., Agrawal A., Ahmad T., Akinyemi R.O., Alahdab F., Al-Aly Z., Alam K., Albertson S.B., Alemu Y.M., Alhassan R.K., Ali M., Ali S., Alipour V., Aljunid S.M., Alla F., Almadi M.A.H., Almasi A., Almasi-Hashiani A., Almasri N.A., Al-Mekhlafi H.M., Almulhim A.M., Alonso J., Al-Raddadi R.M., Altirkawi K.A., Alvis-Guzman N., Alvis-Zakzuk N.J., Amini S., Amini-Rarani M., Amiri F., Amit A.M.L., Amugsi D.A., Ancuceanu R., Anderlini D., Andrei C.L., Androudi S., Ansari F., Ansari-Moghaddam A., Antonio C.A.T., Antony C.M., Antriyandarti E., Anvari D., Anwer R., Arabloo J., Arab-Zozani M., Aravkin A.Y., Aremu O., Arnlov J., Asaad M., Asadi-Aliabadi M., Asadi-Pooya A.A., Athari S.S., Atout M.M.W., Ausloos M., Avila-Burgos L., Ayala Quintanilla B.P., Ayano G., Ayanore M.A., Aynalem Y.A., Aynalem G.L., Ayza M.A., Azari S., Azzopardi P.S., B D.B., Babaee E., Badiye A.D., Bahrami M.A., Baig A.A., Bakhshaei M.H., 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S., Gardner W.M., Geberemariyam B.S., Gebrehiwot A.M., Gebremeskel L.G., Gebremeskel G.G., Gesesew H.A., Ghadiri K., Ghafourifard M., Ghashghaee A., Ghith N., Gholamian A., Gilani S.A., Gill P.S., Gill T.K., Ginindza T.G., Gitimoghaddam M., Giussani G., Glagn M., Gnedovskaya E.V., Godinho M.A., Goharinezhad S., Gopalani S.V., Goudarzian A.H., Goulart B.N.G., Gubari M.I.M., Guimaraes R.A., Guled R.A., Gultie T., Guo Y., Gupta R., Hafezi-Nejad N., Hafiz A., Haile T.G., Hamadeh R.R., Hameed S., Hamidi S., Han C., Han H., Handiso D.W., Hanif A., Hankey G.J., Haro J.M., Hasaballah A.I., Hasan M.M., Hashi A., Hassan S., Hassan A., Hassanipour S., Hassankhani H., Havmoeller R.J., Hay S.I., Hayat K., Heidari G., Heidari-Soureshjani R., Hendrie D., Herteliu C., Hird T.R., Ho H.C., Hole M.K., Holla R., Hoogar P., Hopf K.P., Horita N., Hossain N., Hosseini M., Hosseinzadeh M., Hostiuc M., Hostiuc S., Househ M., Hsieh V.C.-R., Hu G., Huda T.M., Humayun A., Hwang B.-F., Iavicoli I., Ibitoye S.E., Ikeda N., Ilesanmi O.S., Ilic M.D., Inbaraj L.R., Iqbal U., Irvani S.S.N., Irvine C.M.S., Islam M.M., Islam S.M.S., Islami F., Iso H., Iwu C.J., Jaafari J., Jadidi-Niaragh F., Jafarinia M., Jahagirdar D., Jahani M.A., Jahanmehr N., Jakovljevic M., Janjani H., Javaheri T., Jayatilleke A.U., Jenabi E., Jha R.P., Jha V., Ji J.S., Jia P., John-Akinola Y.O., Jonas J.B., Joukar F., Jozwiak J.J., Jurisson M., Kabir Z., Kalankesh L.R., Kalhor R., Kamath A.M., Kanchan T., Kapoor N., Karami Matin B., Karanikolos M., Karimi S.M., Kassebaum N.J., Katikireddi S.V., Kayode G.A., Keiyoro P.N., Khader Y.S., Khammarnia M., Khan M., Khan E.A., Khang Y.-H., Khatab K., Khater A.M., Khater M.M., Khatib M.N., Khayamzadeh M., Khubchandani J., Kianipour N., Kim Y.J., Kimokoti R.W., Kinfu Y., Kisa A., Kissimova-Skarbek K., Kivimaki M., Kneib C.J., Kocarnik J.M., Kochhar S., Kohler S., Kopec J.A., Korotkova A.V., Korshunov V.A., Kosen S., Kotlo A., Koul P.A., Koyanagi A., Krishan K., Krohn K.J., Kugbey N., Kulkarni V., Kumar G.A., Kumar N., Kumar M., Kurmi O.P., Kusuma D., Kyu H.H., La Vecchia C., Lacey B., Lal D.K., Lalloo R., Landires I., Lansingh V.C., Larsson A.O., Lasrado S., Lau K.M.-M., Lauriola P., Lazarus J.V., Ledesma J.R., Lee P.H., Lee S.W.H., Leever A.T., LeGrand K.E., Leigh J., Leonardi M., Li S., Lim S.S., Lim L.-L., Liu X., Logroscino G., Lopez A.D., Lopukhov P.D., Lotufo P.A., Lu A., Ma J., Madadin M., Mahasha P.W., Mahmoudi M., Majeed A., Malagon-Rojas J.N., Maleki S., Malta D.C., Mansouri B., Mansournia M.A., Martini S., Martins-Melo F.R., Martopullo I., Massenburg B.B., Mastrogiacomo C.I., Mathur M.R., McAlinden C., McKee M., Medina-Solis C.E., Meharie B.G., Mehndiratta M.M., Mehrabi Nasab E., Mehri F., Mehrotra R., Mekonnen T., Melese A., Memiah P.T.N., Mendoza W., Menezes R.G., Mensah G.A., Meretoja T.J., Meretoja A., Mestrovic T., Miazgowski B., Michalek I.M., Mirrakhimov E.M., Mirzaei M., Mirzaei-Alavijeh M., Mitchell P.B., Moazen B., Moghadaszadeh M., Mohamadi E., Mohammad Y., Mohammad D.K., Mohammad Gholi Mezerji N., Mohammadian-Hafshejani A., Mohammed S., Mohammed J.A., Mokdad A.H., Monasta L., Mondello S., Moradi M., Moradi-Lakeh M., Moradzadeh R., Moraga P., Morgado-da-Costa J., Morrison S.D., Mosapour A., Mosser J.F., Mousavi Khaneghah A., Muriithi M.K., Mustafa G., Nabhan A.F., Naderi M., Nagarajan A.J., Naghavi M., Naghshtabrizi B., Naimzada M.D., Nangia V., Nansseu J.R., Nayak V.C., Nazari J., Ndejjo R., Negoi I., Negoi R.I., Neupane S., Ngari K.N., Nguefack-Tsague G., Ngunjiri J.W., Nguyen C.T., Nguyen D.N., Nguyen H.L.T., Nnaji C.A., Nomura S., Norheim O.F., Noubiap J.J., Nowak C., Nunez-Samudio V., Otoiu A., Ogbo F.A., Oghenetega O.B., Oh I.-H., Okunga E.W., Oladnabi M., Olagunju A.T., Olusanya J.O., Olusanya B.O., Oluwasanu M.M., Omar Bali A., Omer M.O., Ong K.L., Onwujekwe O.E., Ortega-Altamirano D.V.V., Ortiz A., Ostojic S.M., Otstavnov N., Otstavnov S.S., Overland S., Owolabi M.O., Padubidri J.R., Pakhale S., Palladino R., Pana A., Panda-Jonas S., Pangaribuan H.U., Pathak M., Patton G.C., Paudel S., Pazoki Toroudi H., Pease S.A., Peden A.E., Pennini A., Peprah E.K., Pereira J., Pigott D.M., Pilgrim T., Pilz T.M., Pinheiro M., Piradov M.A., Pirsaheb M., Pokhrel K.N., Postma M.J., Pourjafar H., Pourmalek F., Pourmirza Kalhori R., Pourshams A., Prada S.I., Pribadi D.R.A., Pupillo E., Quazi Syed Z., Radfar A., Rafiee A., Rafiei A., Raggi A., Rahim F., Rahman M.A., Rajabpour-Sanati A., Rana S.M., Ranabhat C.L., Rao S.J., Rasella D., Rashedi V., Rath G.K., Rathi P., Rawaf S., Rawaf D.L., Rawal L., Rawassizadeh R., Razo C., Renjith V., Renzaho A.M.N., Reshmi B., Rezaei N., Riahi S.M., Ribeiro D.C., Rickard J., Roberts N.L.S., Roever L., Romoli M., Ronfani L., Roshandel G., Rubagotti E., Rwegerera G.M., Sabour S., Sachdev P.S., Saddik B., Sadeghi M., Sadeghi E., Safari Y., Sagar R., Sahebkar A., Sahraian M.A., Sajadi S.M., Salahshoor M.R., Salem M.R.R., Salem H., Salomon J., Samadi Kafil H., Samy A.M., Sanabria J., Santric-Milicevic M.M., Saraswathy S.Y.I., Sarmiento-Suarez R., Sartorius B., Sarveazad A., Sathian B., Sathish T., Sattin D., Savic M., Sawyer S.M., Saxena D., Sbarra A.N., Schaeffer L.E., Schiavolin S., Schmidt M.I., Schutte A.E., Schwebel D.C., Schwendicke F., Seedat S., Sha F., Shahabi S., Shaheen A.A., Shaikh M.A., Shamsizadeh M., Shannawaz M., Sharafi K., Sharara F., Sharifi H., Shaw D.H., Sheikh A., Sheikhtaheri A., Shibuya K., Shiferaw W.S., Shigematsu M., Shin J.I., Shiri R., Shirkoohi R., Shivakumar K.M., Shrime M.G., Shuval K., Siabani S., Sierpinski R., Sigfusdottir I.D., Sigurvinsdottir R., Silva D.A.S., Silva J.P., Simonetti B., Simpson K.E., Singh J.A., Singh P., Sinha D.N., Skryabin V.Y., Smith E.U.R., Soheili A., Soltani S., Soofi M., Sorensen R.J.D., Soriano J.B., Sorrie M.B., Soyiri I.N., Spurlock E.E., Sreeramareddy C.T., Stanaway J.D., and Steel N.
Abstract: Background: Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Method(s): Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (>=65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2.5th and 97.5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UH
Published: 2020

35. Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019.

Author: Hird T.R., Shannawaz M., Sharma R., Shin J., Shiri R., Sierpinski R., Sigurvinsdottir R., Silva D.A.S., Simonetti B., Singh A., Sinha D.N., Skiadaresi E., Skou S.T., Skryabin V.Y., Zastrozhin M.S., Soheili A., Sokhan A., Somefun O.D., Korotkova A.V., Soyiri I.N., Sreeramareddy C.T., Srinivasan V., Sripada K., Stovner L.J., Stockfelt L., Sultan I., Swope C.B., Vaicekonyte R., Sykes B.L., Szumowski L., Tabb K.M., Tabuchi T., Taddele B.W., Tahir Z., Tareque M.I., Tarigan I.U., Taveira N., Thankappan K.R., Thomas N., Varughese S., Touvier M., Tran B.X., Tsatsakis A., Vardavas C., Ullah I., Umeokonkwo C.D., Undurraga E.A., Upadhyay E., Vasankari T.J., Vasconcelos A.N., Veisani Y., Vidale S., Waheed Y., Wei J., Wang F., Zhao X.G., Wang Y., Yu C., Zhang Z., Wang H., Weiss J., Wiangkham T., Wickramasinghe N.D., Wu A., Xie Y., Xu G., Yahyazadeh Jabbari S., Yilgwan C.S., Yonemoto N., Younis M.Z., Younker T.P., Yu Y., Zaidi S., Zhang J., Zhang Y., Zheleva B., Zhu C., Abbafati C., Machado D.B., Cislaghi B., Salman O.M., Karanikolos M., McKee M., Abbas K.M., Brady O.J., Larson H.J., Trias-Llimos S., Cummins S., Langan S.M., Sartorius B., Hafiz A., Jenabi E., Mohammad Gholi Mezerji N., Borzouei S., Azarian G., Khazaei S., Abbasi M., Asghari B., Masoumi S., Komaki H., Taherkhani A., Adabi M., Abbasifard M., Bazmandegan G., Kamiab Z., Vakilian A., Anjomshoa M., Mokari A., Sabour S., Shahbaz M., Saeedi R., Ahmadieh H., Yousefinezhadi T., Haj-Mirzaian A., Nikbakhsh R., Safi S., Asgari S., Irvani S.N., Jahanmehr N., Ramezanzadeh K., Abbasi-Kangevari M., Khayamzadeh M., Abbastabar H., Shirkoohi R., Fazlzadeh M., Janjani H., Hosseini M., Mansournia M., Tohidinik H., Bakhtiari A., Fazaeli A., Mousavi S., Hasanzadeh A., Nabavizadeh B., Malekzadeh R., Hashemian M., Pourshams A., Salimzadeh H., Sepanlou S.G., Afarideh M., Esteghamati A., Esteghamati S., Ghajar A., Heidari B., Rezaei N., Mohamadi E., Rahimi-Movaghar A., Rahim F., Eskandarieh S., Sahraian M., Mohebi F., Aminorroaya A., Ebrahimi H., Farzadfar F., Mohajer B., Pishgar F., Saeedi Moghaddam S., Shabani M., Zarafshan H., Abolhassani H., Hafezi-Nejad N., Heidari-Soureshjani R., Abdollahi M., Farahmand M., Salamati P., Mehrabi Nasab E., Tajdini M., Aghamir S., Mirzaei R., Dibaji Forooshani Z., Khater M.M., Abd-Allah F., Abdelalim A., Abualhasan A., El-Jaafary S.I., Hassan A., Elsharkawy A., Khater A.M., Elhabashy H.R., Salem M.R.R., Salem H., Sadeghi M., Jafarinia M., Amini-Rarani M., Mohammadifard N., Sarrafzadegan N., Abdollahpour I., Sarveazad A., Tehrani-Banihashemi A., Yoosefi Lebni J., Manafi N., Pazoki Toroudi H., Dorostkar F., Alipour V., Sheikhtaheri A., Arabloo J., Azari S., Ghashghaee A., Rezapour A., Naserbakht M., Kabir A., Mehri F., Yousefifard M., Asadi-Aliabadi M., Babaee E., Eshrati B., Goharinezhad S., Moradi M., Abedi P., Rashedi V., Kumar V., Elgendy I.Y., Basu S., Park J., Pereira A., Norheim O.F., Eagan A.W., Cahill L.E., Sheikh A., Abushouk A.I., Thakur B., Barnighausen T.W., Shrime M.G., Abedi A., Doshi C.P., Abegaz K.H., Geberemariyam B.S., Aynalem Y.A., Shiferaw W.S., Abosetugn A.E., Aboyans V., Abrams E.M., Gitimoghaddam M., Kissoon N., Stubbs J.L., Brauer M., Iyamu I.O., Kopec J.A., Pourmalek F., Ribeiro A.P., Malta D.C., Gomez R.S., Abreu L.G., Abrigo M.R.M., Almulhim A.M., Dahlawi S.M.A., Pottoo F.H., Menezes R.G., Alanzi T.M., Alumran A.K., Abu Haimed A.K., Madadin M., Alanezi F.M., Abu-Gharbieh E., Saddik B., Abu-Raddad L.J., Samy A.M., El Nahas N., Shalash A.S., Nabhan A.F., Kamath A.M., Kassebaum N.J., Aravkin A.Y., Kochhar S., Sorensen R.J.D., Afshin A., Burkart K., Cromwell E.A., Gakidou E., Hay S.I., Kyu H.H., Lopez A.D., Lozano R., Misganaw A.T., Mokdad A.H., Naghavi M., Pigott D.M., Reiner Jr R.C., Roth G.A., Stanaway J.D., Vollset S., Vos T., Lim S.S., Murray C.J.L., Kalani R., Ikuta K.S., Cho D.Y., Kneib C.J., Crowe C.S., Massenburg B.B., Morrison S.D., Acebedo A., Adelson J.D., Agesa K.M., Alam T., Albertson S.B., Anderson J.A., Antony C.M., Ashbaugh C., Assmus M., Azhar G., Balassyano S., Bannick M.S., Barthelemy C.M., Bender R.G., Bennitt F.B., Bertolacci G.J., Biehl M.H., Bisignano C., Boon-Dooley A.S., Briant P.S., Bryazka D., Bumgarner B.R., Callender C.S., Cao J., Castle C.D., Castro E., Causey K., Cercy K.M., Chalek J., Cohen A.J., Comfort H., Compton K., Croneberger A.J., Cruz J.A., Cunningham M., Dangel W.J., Dean F.E., DeCleene N.K., Deen A., Degenhardt L., Dingels Z.V., Dippenaar I.N., Dirac M.A., Dolgert A.J., Emmons-Bell S., Estep K., Farag T., Feigin V.L., Feldman R., Ferrara G., Ferrari A.J., Fitzgerald R., Force L.M., Fox J.T., Frank T.D., Fu W., Fukutaki K., Fuller J.E., Fullman N., Galles N.C., Gardner W.M., Gershberg Hayoon A., Goren E., Gorman T.M., Gottlich H.C., Guo G., Haddock B., Hagins H., Haile L.M., Hamilton E.B., Han C., Han H., Harvey J.D., Henny K., Henrikson H.J., Henry N.J., Herbert M.E., Hsiao T., Huynh C.K., Iannucci V.C., Ippolito H., Irvine C.M.S., Jafari H., Jahagirdar D., James S.L., Johnson C.O., Johnson S.C., Keller C., Kemmer L., Kendrick P.J., Knight M., Kocarnik J.M., Krohn K.J., Larson S.L., Lau K.M., Ledesma J.R., Leever A.T., LeGrand K.E., Lescinsky H., Lin C., Liu H., Liu Z., Lo J., Lu A., Ma J., Maddison E.R., Manguerra H., Marks A., Martopullo I., Mastrogiacomo C.I., May E.A., Mooney M.D., Mosser J.F., Mullany E.C., Mumford J., Munro S.B., Nandakumar V., Nguyen J., Nguyen M., Nichols E., Nixon M.R., Odell C.M., Ong K.L., Orji A.U., Ostroff S.M., Pasovic M., Paulson K.R., Pease S.A., Pennini A., Pierce M., Pilz T.M., Pletcher M., Rao P.C., Razo C., Redford S.B., Reinig N., Reitsma M.B., Rhinehart P., Robalik T., Roberts N.L.S., Rolfe S., Sbarra A.N., Schaeffer L.E., Shackelford K.A., Shadid J., Sharara F., Shaw D.H., Sheena B.S., Simpson K.E., Smith A., Spencer C.N., Spurlock E.E., Stark B.A., Steiner C., Steuben K.M., Sylte D.O., Tang M., Taylor H.J., Terrason S., Thomson A.M., Torre A.E., Travillian R., Troeger C.E., Vongpradith A., Walters M.K., Wang J., Watson A., Watson S., Whisnant J.L., Whiteford H.A., Wiens K.E., Wilner L.B., Wilson S., Wool E.E., Wozniak S.S., Wu J., Wulf Hanson S., Wunrow H., Xu R., Yadgir S., Yearwood J.A., York H.W., Yuan C., Zhao J.T., Zheng P., Zimsen S.R.M., Zlavog B.S., Chang A.Y., Oren E., Buchbinder R., Chin K.L., Guo Y., Polkinghorne K.R., Thrift A.G., Ackerman I.N., Cicuttini F.M., Li S., Zaman S., Suleria H., Cowie B.C., Wijeratne T., Patton G.C., Sawyer S.M., Adair T., Meretoja A., Adetokunboh O.O., Adamu A.A., Iwu C.J., Parry C.D.H., Seedat S., Ndwandwe D.E., Mahasha P.W., Stein D.J., Nnaji C.A., Sambala E.Z., Wiysonge C.S., Adebayo O.M., Ilesanmi O.S., Owolabi M.O., Adeoye A.M., Adedeji I.A., Adekanmbi V., Ibitoye S.E., John-Akinola Y.O., Oluwasanu M.M., Oghenetega O.B., Akinyemi R.O., Zandian H., Adham D., Zahirian Moghadam T., Advani S.M., Teagle W.L., Braithwaite D., Agasthi P., Saadatagah S., Afshari M., Agardh E.E., Allebeck P., Danielsson A., Deuba K., Carrero J.J., Fereshtehnejad S., Arnlov J., Nowak C., Cederroth C.R., Ahmadi A., Mills E.J., Kurmi O.P., Olagunju A.T., Agarwal G., Sathish T., Aghaali M., Mohammadbeigi A., Agrawal A., Ahmad T., Ahmadi K., Maleki S., Naderi M., Salahshoor M.R., Pourmirza Kalhori R., Almasi A., Salimi Y., Siabani S., Ziapour A., Barzegar A., Khazaie H., Kianipour N., Amiri F., Salehi Zahabi S., Mirzaei M., Shamsi M., Najafi F., Jalali A., Ghadiri K., Heydarpour F., Fattahi N., Karami Matin B., Kazemi Karyani A., Pirsaheb M., Rajati F., Sadeghi E., Safari Y., Sharafi K., Soltani S., Vasseghian Y., Atafar Z., Jalilian F., Mirzaei-Alavijeh M., Saeidi S., Soofi M., Zangeneh A., Mansouri B., Ahmadi M., Khafaie M.A., Safiri S., Moghadaszadeh M., Asghari Jafarabadi M., Doshmangir L., Jadidi-Niaragh F., Ghafourifard M., Spotin A., Khodayari M., Samadi Kafil H., Kalankesh L.R., Ahmadpour E., Yousefi B., Ansari F., Hassankhani H., Karimi S., Haririan H., Mereta S., Ahmed M.B., Feyissa G.T., Ciobanu L.G., Aji B., Aynalem G.L., Gebresillassie B., Tefera Y.G., Akalu T.Y., Baraki A.G., Tesema G.A., Tessema Z.T., Tamiru A.T., Azene Z.N., Netsere H.B., Yano Y., Akinyemiju T., Wu C., Zadey S., Samad Z., Ji J.S., Doshi P.P., John O., Jha V., Maulik P.K., Pesudovs K., Resnikoff S., Mitchell P.B., Sachdev P.S., Akombi B., Godinho M.A., Ivers R.Q., Peden A.E., Biswas R., Boufous S., Akunna C.J., Alahdab F., Hammer M.S., van Donkelaar A., Al-Aly Z., Dellavalle R.P., Alam S., Martin R.V., Alam N., De Leo D., Tadakamadla S.K., Alam K., Alcalde-Rabanal J.E., Avila-Burgos L., Servan-Mori E., Denova-Gutierrez E., Rodriguez-Ramirez S., Morales L., Poznanska A., Wojtyniak B., Rivera J.A., Campos-Nonato I.R., Campuzano Rincon J., Sanchez-Pimienta T.G., Mengesha M.B., Welay F.T., Alema N.M., Demsie D.G., Teame H., Teklehaimanot B.F., Alemu B.W., Gultie T., Bante A.B., Yeshitila Y.G., Geramo Y.C.D., Glagn M., Sorrie M.B., W/hawariat F.G., Amare A., Kasa A., Alemu Y., Mihretie K.M., Atnafu D.D., Demeke F.M., Melese A., Bante S.A., Dessie G.A., Mengesha E.W., Nigatu D., Almadi M.A.H., Alhabib K.F., Mohammad Y., Altirkawi K.A., Temsah M., Kugbey N., Ayanore M.A., Alhassan R.K., Ali M., Ali S., Alicandro G., Kalhor R., Alijanzadeh M., Alinia C., Yusefzadeh H., Didarloo A., Alizade H., Nikpoor A., Aljunid S.M., Alla F., Leal L.F., Almasi-Hashiani A., Moradzadeh R., Zamanian M., Nazari J., Amini S., Ghamari F., Almasri N.A., Khan M., Al-Mekhlafi H.M., Bedi N., Alonso J., Ciber E.S.P., Al-Raddadi R.M., Zakzuk J., Alvis-Guzman N., Alvis-Zakzuk N.J., Castaneda-Orjuela C.A., Malagon-Rojas J.N., Gezae K., Gesesew H.A., Muthupandian S., Berhe K., Amare B., Ayza M.A., Gebreslassie A.A.A., Bitew H., Zewdie K.A., Tela F.G.G., Gill T.K., Noubiap J., Lassi Z.S., Bhandari D., Amit A.L., Antonio C.T., Faraon E.A., Lopez J.F., Atre S.R., Ballew S.H., Matsushita K., Khoja A.T., Daneshpajouhnejad P., Ghadimi M., Shafaat O., Fanzo J., Amugsi D.A., Amul G.H., Koh D.S.Q., Venketasubramanian N., Anbesu E.W., Mohammed J.A., Wondmeneh T.G., Andrei C., Negoi R.I., Davitoiu D.V., Manda A., Negoi I., Preotescu L., Hostiuc M., Hostiuc S., Ancuceanu R., Hasan M., Leung J., Anderlini D., Mamun A.A., Maravilla J.C., McGrath J.J., Charlson F.J., Lalloo R., Uddin R., Erskine H.E., Knibbs L.D., Mantilla Herrera A.M., Santomauro D.F., Mirica A., Ausloos M., Herteliu C., Otoiu A., Pana A., Andrei T., Stefan S., Androudi S., Angus C., Ansari I., Pourjafar H., Shams-Beyranvand M., Ansari-Moghaddam A., Khammarnia M., Antonazzo I., Ferrara P., Conti S., Cortesi P.A., Fornari C., Lee P.H., Antriyandarti E., Yousefi Z., Rafiei A., Javidnia J., Faridnia R., Anvari D., Moosazadeh M., Rezai M., Daryani A., Fareed M., Anwer R., Appiah S., Paudel D., Dichgans M., Riahi S., Rajabpour-Sanati A., Arab-Zozani M., Arba A.A.K., Aremu O., Ariani F., Aripov T., Armoon B., Mahdavi M.M., Arowosegbe O.O., Tediosi F., Aryal K.K., Mosapour A., Yaminfirooz M., Arzani A., Bijani A., Jahani M.A., Mouodi S., Zamani M., Asaad M., Dianatinasab M., Bahrami M., Pakshir K., 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A.E., Biswas R., Boufous S., Akunna C.J., Alahdab F., Hammer M.S., van Donkelaar A., Al-Aly Z., Dellavalle R.P., Alam S., Martin R.V., Alam N., De Leo D., Tadakamadla S.K., Alam K., Alcalde-Rabanal J.E., Avila-Burgos L., Servan-Mori E., Denova-Gutierrez E., Rodriguez-Ramirez S., Morales L., Poznanska A., Wojtyniak B., Rivera J.A., Campos-Nonato I.R., Campuzano Rincon J., Sanchez-Pimienta T.G., Mengesha M.B., Welay F.T., Alema N.M., Demsie D.G., Teame H., Teklehaimanot B.F., Alemu B.W., Gultie T., Bante A.B., Yeshitila Y.G., Geramo Y.C.D., Glagn M., Sorrie M.B., W/hawariat F.G., Amare A., Kasa A., Alemu Y., Mihretie K.M., Atnafu D.D., Demeke F.M., Melese A., Bante S.A., Dessie G.A., Mengesha E.W., Nigatu D., Almadi M.A.H., Alhabib K.F., Mohammad Y., Altirkawi K.A., Temsah M., Kugbey N., Ayanore M.A., Alhassan R.K., Ali M., Ali S., Alicandro G., Kalhor R., Alijanzadeh M., Alinia C., Yusefzadeh H., Didarloo A., Alizade H., Nikpoor A., Aljunid S.M., Alla F., Leal L.F., Almasi-Hashiani A., Moradzadeh R., Zamanian M., Nazari J., Amini S., Ghamari F., Almasri N.A., Khan M., Al-Mekhlafi H.M., Bedi N., Alonso J., Ciber E.S.P., Al-Raddadi R.M., Zakzuk J., Alvis-Guzman N., Alvis-Zakzuk N.J., Castaneda-Orjuela C.A., Malagon-Rojas J.N., Gezae K., Gesesew H.A., Muthupandian S., Berhe K., Amare B., Ayza M.A., Gebreslassie A.A.A., Bitew H., Zewdie K.A., Tela F.G.G., Gill T.K., Noubiap J., Lassi Z.S., Bhandari D., Amit A.L., Antonio C.T., Faraon E.A., Lopez J.F., Atre S.R., Ballew S.H., Matsushita K., Khoja A.T., Daneshpajouhnejad P., Ghadimi M., Shafaat O., Fanzo J., Amugsi D.A., Amul G.H., Koh D.S.Q., Venketasubramanian N., Anbesu E.W., Mohammed J.A., Wondmeneh T.G., Andrei C., Negoi R.I., Davitoiu D.V., Manda A., Negoi I., Preotescu L., Hostiuc M., Hostiuc S., Ancuceanu R., Hasan M., Leung J., Anderlini D., Mamun A.A., Maravilla J.C., McGrath J.J., Charlson F.J., Lalloo R., Uddin R., Erskine H.E., Knibbs L.D., Mantilla Herrera A.M., Santomauro D.F., Mirica A., Ausloos M., Herteliu C., Otoiu A., Pana A., Andrei T., Stefan S., Androudi S., Angus C., Ansari I., Pourjafar H., Shams-Beyranvand M., Ansari-Moghaddam A., Khammarnia M., Antonazzo I., Ferrara P., Conti S., Cortesi P.A., Fornari C., Lee P.H., Antriyandarti E., Yousefi Z., Rafiei A., Javidnia J., Faridnia R., Anvari D., Moosazadeh M., Rezai M., Daryani A., Fareed M., Anwer R., Appiah S., Paudel D., Dichgans M., Riahi S., Rajabpour-Sanati A., Arab-Zozani M., Arba A.A.K., Aremu O., Ariani F., Aripov T., Armoon B., Mahdavi M.M., Arowosegbe O.O., Tediosi F., Aryal K.K., Mosapour A., Yaminfirooz M., Arzani A., Bijani A., Jahani M.A., Mouodi S., Zamani M., Asaad M., Dianatinasab M., Bahrami M., Pakshir K., Asadi-Pooya A.A., Bayati M., Shahabi S., Athari S., Atout M.M.W., Atteraya M.S., Brugha T., Ausloos F., Avokpaho E.F.G., Room R., Islam M., Edvardsson D., Rahman M., Ayala Quintanilla B., Gething P.W., Briggs A.M., Ayano G., Hendrie D., Miller T.R., Azzopardi P.S., Hoogar P., B D.B., Kulkarni V., Kumar N., Mithra P., Shetty R.S., Thapar R., Padubidri J., Bakkannavar S.M., Nayak V.C., Rastogi P., Shetty B.K., Bhageerathy R., Gudi N., Boloor A., Holla R., Rathi P., Unnikrishnan B., Janodia M.D., Lang J.J., Badawi A., Orpana H.M., Bhutta Z.A., Shield K.D., Chattu V., Badiye A.D., Kapoor N., Bagherzadeh M., Rabiee N., Bagli E., Baig A.A., Bairwa M., Lodha R., Sagar R., Rath G.K., Bhardwaj P., Charan J., Kanchan T., Joshi A., Pakhare A.P., Bakhshaei M., Naghshtabrizi B., Balachandran A., Hoek H.W., Postma M.J., Geremew A., Gebrehiwot A.M., Balakrishnan S., Desalew A., Bojia H.A., Mohammed A.S., Regassa L.D., Parmar P.G.K., Balalla S., Roberts S., Baldasseroni A., Stokes M.A., Ball K., Islam S., Maddison R., Balzi D., Levi M., Banach M., Banerjee S.K., Banik P.C., Barua L., Faruque M., Barboza M.A., Barker-Collo S.L., Jonas J.B., Panda-Jonas S., De Neve J., Kohler S., Moazen B., Mohammed S., Barrero L.H., Basaleem H., Bassat Q., Haro J.M., Koyanagi A., Car J., Greaves F., Majeed A., Davis A.C., Steiner T.J., Kusuma D., Palladino R., Saxena S., Baune B.T., Karch A., Baye B.A., Darega Gela J., Kolola T., Becker J.S., DeLang M., West J., Gad M.M., Serre M.L., Gallus S., Lugo A., Beghi E., Pupillo E., Bosetti C., Giussani G., Bikbov B., Perico N., Remuzzi G., Imani-Nasab M., Nouraei Motlagh S., Sharafi Z., Behzadifar M., Bejot Y., Bekuma T.T., Yilma M.T., Bell M.L., Bello A.K., Rafiee A., Keddie S.H., Lucas T.C.D., Dolecek C., Dunachie S.J., Kraemer M.U.G., Rumisha S.F., Weiss D.J., Lewington S., Collins E.L., Nandi A.K., Zhao Y., Bennett D.A., Karim M.A., Lacey B., Khundkar R., Yaya S., Goulart A.C., Santos I.S., Bensenor I.M., Lotufo P.A., Tovani-Palone M.R., Castaldelli-Maia J., Furtado J.M., Benziger C.P., Berman A.E., Mazidi M., Bernabe E., Dargan P.I., Molokhia M., Shibuya K., Douiri A., Wolfe C.D.A., Hay R.J., Flohr C., Suchdev P.S., Ram P., Bernstein R.S., Liu Y., Bhagavathula A.S., Khan G., Grivna M., Bhala N., Chandan J.S., Gaidhane A.M., Quazi Syed Z., Saxena D., Khatib M., Bhat A.G., Bhattacharyya K., Bhattarai S., Das J.K., Bibi S., Bilano V., Bin Sayeed M., Cherbuin N., D'Amico E., Grosso G., Borzi A.M., Biondi A., Vacante M., Valli A., Birihane B.M., Bisanzio D., Hassan S., Bjorge T., Overland S., Bockarie M.J., Mensah G.A., Sliwa K., Gholamian A., Bohlouli S., Esmaeilnejad S., Bohluli M., Bolla S.R., Borges G., Bose D., Bourne R., Brayne C., Breitborde N.J.K., Fisher J.L., Breitner S., Brenner H., Breusov A.V., Rakovac I., Briko N.I., Lopukhov P.D., Glushkova E.V., Korshunov V.A., Polibin R.V., Jakovljevic M., Briko A.N., Britton G.B., Castro F., Moreno Velasquez I., Burnett R.T., Burugina Nagaraja S., Busse R., Butt Z.A., Caetano dos Santos F., Cai T., Hall B.J., Cahuana-Hurtado L., Camera L.A., Valdez P.R., Tudor Car L., Cardenas R., Gorini G., Carreras G., Fernandes E., Freitas M., Pereira D.M., Santos J.V., Ribeiro D., Pinheiro M., Massano J., das Neves J., Dias da Silva D., Carvalho F., Costa V.M., Silva J.P., Morgado-da-Costa J., Castelpietra G., Catala-Lopez F., Pakhale S., Cerin E., Yip P., Ho H., Chang J., Chang A.R., Chang K., Cooper O.R., Chaturvedi S., Chimed-Ochir O., Chirinos-Caceres J.L., Choi J.J., Christensen H., Truelsen T.C., Chu D., Kivimaki M., Chung S., Ward J.L., Chung M.T., Cirillo M., Virclo R., Classen T.K.D., Lauriola P., Corso B., Hugo F.N., Kieling C., Cousin E., Duncan B.B., Goulart B.N.G., Schmidt M.I., Stein C., Cowden R.G., MacLachlan J.H., Leigh J., Cross M., Ferreira M.L., Smith E.U.R., Driscoll T.R., Huda T.M., Hoy D.G., Horita N., Cross D.H., Dai H., Hu G., Damasceno A.A.M., Damiani G., La Vecchia C., Sanabria J., Pandey A., Mathur M.R., Zodpey S., Dandona L., Dandona R., Kumar G., Lal D.K., Hamagharib Abdullah K., Hosseinzadeh M., Darwesh A.M., Faraj A., Omar Bali A., Das Gupta R., Dash A.P., Davey G., Deribe K., Gebremedhin K.B., Wondmieneh A.B., Dereje N.D., Davila-Cervantes C.A., Davletov K., Mereke A., Serdar B., Gebremeskel G.G., Haile T.G., Tadesse D.B., Weldesamuel G.T., Demoz G.T., Gebremeskel L.G., Woldu G., Handiso D., Dervenis N., Topouzis F., Desai R., Dharmaratne S.D., Dhungana G.P., Emamian M., Diaz D., Djalalinia S., Nguyen T.H., Vu G.T., Do H.T., Dokova K., Doku D.T., Neupane S., Takala J.S., Doxey M.C., Doyle K.E., Renzaho A.M.N., Ogbo F.A., Robinson S.R., Vukovic A., Ilic I.M., Santric-Milicevic M.M., Vujcic I.S., Dubljanin E., Vukovic R., Rasella D., Duraes A.R., Ebrahimi Kalan M., Effiong A., Pond C.D., Ehrlich J.R., Liu X., Wei M.Y.W., El Sayed I., El Tantawi M., El Sayed Zaki M., Elbarazi I., Tsai A.C., Elyazar I.R., Yazdi-Feyzabadi V., Eskandari K., Sharifi H., Halvaei I., Ghaffarifar F., Zaki L., Hasanpoor E., Esmaeilzadeh F., Etemadi A., Lan Q., Yeheyis T.Y., Etisso A.E., Ezekannagha O., e Farinha C.S., Farioli A., Violante F.S., Faris P.S., Mohammad D.K., Faro A., Lam J.O., Filip I., Fischer F., Flor L.S., Foigt N.A., Folayan M.O., Fomenkov A.A., Foroutan M., Francis J.M., Franklin R.C., Fukumoto T., Gamkrelidze A., Kereselidze M., Garcia-Basteiro A.L., Lazarus J.V., Straif K., Ghiasvand H., Ghith N., Norrving B., Mehta K.M., Mohamad O., Salama J.S., Ghosh R., Giampaoli S., Gilani S., Hameed S., Hanif A., Rana S.M., Uthman O.A., Gill P.S., Gillum R.F., Ginawi I.A., Ginindza T.G., Tlou B., Tanser F.C., Gnedovskaya E.V., Kravchenko M.A., Piradov M.A., Golechha M., Goli S., Milne G.J., Schlaich M.P., Hankey G.J., Gona P.N., Gopalani S.V., Goudarzi H., Rawassizadeh R., Grada A., Nsoesie E.O., Javaheri T., Rawaf S., Steel N., Gubari M.I.M., Gugnani H.C., Guimaraes A.L.S., Guimaraes R.A., Guled R.A., Senbeta A.M., Hashi A., Omer M.O., Yousuf A.Y., Gupta S.S., Gupta T., Gupta R., Haagsma J.A., Polinder S., Hachinski V., Stranges S., Hamadeh R.R., Hamidi S., Tabares-Seisdedos R., Tyrovolas S., Hasaballah A.I., Hassanipour S., Joukar F., Mansour-Ghanaei F., Jaafari J., Havmoeller R.J., Hayat K., Heibati B., Heidari G., Henok A., Moraga P., Sigfusdottir I.D., Phillips M.R., Hole M.K., Hollingsworth B., Hopf K.P., Hosgood H., Hossain N., Mai H.T., Nguyen C.T., Nguyen H.L.T., Pham H.Q., Nguyen D.N., Househ M., Hsairi M., Lin R., Hsieh V., Hwang B., Hu K., Humayun A., Hussain R., Ibeneme C.U., Ikeda N., Ilic M.D., Inbaraj L.R., Iqbal U., Islami F., Yamagishi K., Iso H., Iwu C.C.D., Jacobsen K.H., Jayatilleke A.U., Jeemon P., Jha R.P., Jia P., Osei F.B., Schutte A.E., Johansson L., Szocska M., Joo T., Jozwiak J.J., Jurisson M., Kabir Z., Roshandel G., Oladnabi M., Kalani H., Kassa G.M., Katikireddi S.V., Yamada T., Nomura S., Kawakami N., Kayode G.A., Kromhout H., Traini E., Kumar M., Keiyoro P.N., Muriithi M.K., Wamai R.G., Khader Y.S., Khalid N., Khan E.A., Khang Y., Khatab K., Khubchandani J., Yoon S., Shin M., Kim C., Kim Y., Kim D., Kimokoti R.W., Kinfu Y., Kisa S., Kisa A., Kissimova-Skarbek K., Topor-Madry R., Lallukka T., Meretoja T.J., Shivakumar K.M., Knudsen A.S., Sulo G., Kosen S., Kotlo A., Koul P.A., Krishan K., KS S., Kuate Defo B., Kucuk Bicer B., Yuce D., Rawat R., Meitei W.B., Kumar P., Singh P., Kumaresh G., Lami F.H., Landires I., Nunez-Samudio V., Landires, Lansingh V.C., Lansky S., Larsson A.O., Lasrado S., Lavados P.M., Leasher J.L., Lee S.W.H., Leonardi M., Raggi A., Sattin PsyD, S Schiavolin D., Li B., Lim L., Takahashi K., Linehan C., Linn S., Shuval K., Listl S., Zhou M., Liu S., Logroscino G., Looker K.J., Lorkowski S., Lunevicius R., Lyons R.A., Madotto F., Magdy Abd El Razek H., Magdy Abd El Razek M., Mahmoudi M., Maled V., Moradi G., Maleki A., Manafi A., Mapoma C., Martini S., Martins-Melo F.R., Masaka A., McAlinden C., Momen N.C., Plana-Ripoll O., Medina-Solis C.E., Meharie B., Mehndiratta M., Mehrotra R., Suliankatchi Abdulkader R., Mekonnen T., Memiah P.T.N., Wallin M.T., Memish Z.A., Mendoza W., Mestrovic T., Miazgowski T., Miazgowski B., Michalek I., Mini G., Miri M., Mirrakhimov E.M., Mirzaei H., Mohammadian-Hafshejani A., Mohammadpourhodki R., Sahebkar A., Mohammed H., Sufiyan M.B., Mohseni Bandpei M.A., Monasta L., Ronfani L., Mondello S., Moradi-Joo M., Morawska L., Mousavi Khaneghah A., Westerman R., Werdecker A., Mueller U.O., Mukhopadhyay S., Musa K., Mustafa G., Nagarajan A.J., Nagel G., Rothenbacher D., Naik G., Schwebel D.C., Singh J.A., Naimzada M., Otstavnov N., Otstavnov S.S., Soshnikov S., Titova M.V., Nair S., Naldi L., Nangia V., Nansseu J., Sobngwi E., Nguefack-Tsague G., Ndejjo R., Ngari K.N., Ngunjiri J.W., Nigatu Y.T., Oancea B., Oh I., Okunga E.W., Olusanya J.O., Olusanya B.O., Ong S., Onwujekwe O.E., Ortega-Altamirano D.V., Ortiz A., Soriano J.B., Osarenotor O., Ostojic S.M., Vlassov V., Pa M., Pangaribuan H.U., Park E., Pasupula D., Patel J.R., Patel S.K., Paternina-Caicedo A.J., Pathak M., Pathak A., Patten S.B., Tonelli M., Weintraub R.G., Paudel S., Pepito V.F., Thurston G.D., Peprah E.K., Pereira J., Pescarini J.M., Piccinelli C., Pilgrim T., Plass D., Pokhrel K.N., Prada S.I., Prakash V., Prakash S., Prasad N., Shigematsu M., Pribadi D.R.A., Sudaryanto A., Rabiee M., Radfar A., Ranabhat C.L., Ranta A., Ribeiro D.C., Rao S., Rawaf D.L., Rawal L., Renjith V., Rickard J., Roever L., Romoli M., Rostamian M., Rubagotti E., Rwegerera G.M., Ullah S., Sajadi S., Salam N., Salomon J.A., Salz I., Saraswathy S.Y., Sarmiento-Suarez R., Sathian B., Savic M., Saylan M., Schwendicke F., Sekerija M., Senthilkumaran S., Sha F., Shaheen A.A., Shaikh M.A., and Shamsizadeh M.
Abstract: Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Method(s): 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a B
Published: 2020

36. Genetic and environmental causes of variation in epigenetic aging across the lifespan.

Author: Thalamuthu A., Milne R.L., Hopper J.L., Southey M.C., Giles G.G., Li S., Nguyen T.L., Wong E.M., Dugue P.-A., Dite G.S., Armstrong N.J., Craig J.M., Mather K.A., Sachdev P.S., Saffery R., Sung J., Tan Q., Thalamuthu A., Milne R.L., Hopper J.L., Southey M.C., Giles G.G., Li S., Nguyen T.L., Wong E.M., Dugue P.-A., Dite G.S., Armstrong N.J., Craig J.M., Mather K.A., Sachdev P.S., Saffery R., Sung J., and Tan Q.
Abstract: Background: DNA methylation-based biological age (DNAm age) is an important biomarker for adult health. Studies in specific age ranges have found widely varying results about its genetic and environmental causes of variation. However, these studies are not able to provide a comprehensive view of the causes of variation over the lifespan. Result(s): In order to investigate the genetic and environmental causes of DNAm age variation across the lifespan, we pooled genome-wide DNA methylation data for 4217 people aged 0-92 years from 1871 families. DNAm age was calculated using the Horvath epigenetic clock. We estimated familial correlations in DNAm age for monozygotic (MZ) twin, dizygotic (DZ) twin, sibling, parent-offspring, and spouse pairs by cohabitation status. Genetic and environmental variance components models were fitted and compared. We found that twin pair correlations were - 0.12 to 0.18 around birth, not different from zero (all P > 0.29). For all pairs of relatives, their correlations increased with time spent living together (all P < 0.02) at different rates (MZ > DZ and siblings > parent-offspring; P < 0.001) and decreased with time spent living apart (P = 0.02) at similar rates. These correlation patterns were best explained by cohabitation-dependent shared environmental factors, the effects of which were 1.41 (95% confidence interval [CI] 1.16 to 1.66) times greater for MZ pairs than for DZ and sibling pairs, and the latter were 2.03 (95% CI 1.13 to 9.47) times greater than for parent-offspring pairs. Genetic factors explained 13% (95% CI - 10 to 35%) of variation (P = 0.27). Similar results were found for another two epigenetic clocks, suggesting that our observations are robust to how DNAm age is measured. In addition, results for the other clocks were consistent with there also being a role for prenatal environmental factors in determining their variation. Conclusion(s): Variation in DNAm age is mostly caused by environmental factors, including thos
Published: 2020

37. Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

Author: Zhang, Q., Sidorenko, J., Couvy-Duchesne, B., Marioni, R.E., Wright, M.J., Goate, A.M., Marcora, E., Huang, K-l, Porter, T., Laws, S.M., Sachdev, P.S., Mather, K.A., Armstrong, N.J., Thalamuthu, A., Brodaty, H., Yengo, L., Yang, J., Wray, N.R., McRae, A.F., Visscher, P.M., Zhang, Q., Sidorenko, J., Couvy-Duchesne, B., Marioni, R.E., Wright, M.J., Goate, A.M., Marcora, E., Huang, K-l, Porter, T., Laws, S.M., Sachdev, P.S., Mather, K.A., Armstrong, N.J., Thalamuthu, A., Brodaty, H., Yengo, L., Yang, J., Wray, N.R., McRae, A.F., and Visscher, P.M.
Abstract: Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer’s disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.
Published: 2020

38. Genetic and environmental determinants of variation in the plasma lipidome of older Australian twins

Author: Wong, M.W.K., Thalamuthu, A., Braidy, N., Mather, K.A., Liu, Y., Ciobanu, L., Baune, B.T., Armstrong, N.J., Kwok, J., Schofield, P., Wright, M.J., Ames, D., Pickford, R., Lee, T., Poljak, A., Sachdev, P.S., Wong, M.W.K., Thalamuthu, A., Braidy, N., Mather, K.A., Liu, Y., Ciobanu, L., Baune, B.T., Armstrong, N.J., Kwok, J., Schofield, P., Wright, M.J., Ames, D., Pickford, R., Lee, T., Poljak, A., and Sachdev, P.S.
Abstract: The critical role of blood lipids in a broad range of health and disease states is well recognised but less explored is the interplay of genetics and environment within the broader blood lipidome. We examined heritability of the plasma lipidome among healthy older-aged twins (75 monozygotic/55 dizygotic pairs) enrolled in the Older Australian Twins Study (OATS) and explored corresponding gene expression and DNA methylation associations. 27/209 lipids (13.3%) detected by liquid chromatography-coupled mass spectrometry (LC-MS) were significantly heritable under the classical ACE twin model (h2 = 0.28–0.59), which included ceramides (Cer) and triglycerides (TG). Relative to non-significantly heritable TGs, heritable TGs had a greater number of associations with gene transcripts, not directly associated with lipid metabolism, but with immune function, signalling and transcriptional regulation. Genome-wide average DNA methylation (GWAM) levels accounted for variability in some non-heritable lipids. We reveal a complex interplay of genetic and environmental influences on the ageing plasma lipidome.
Published: 2020

39. Common genetic variation indicates separate causes for periventricular and deep white matter hyperintensities

Author: Armstrong, N.J., Mather, K.A., Sargurupremraj, M., Knol, M.J., Malik, R., Satizabal, C.L., Yanek, L.R., Wen, W., Gudnason, V.G., Dueker, N.D., Elliott, L.T., Hofer, E., Bis, J., Jahanshad, N., Li, S., Logue, M.A., Luciano, M., Scholz, M., Smith, A.V., Trompet, S., Vojinovic, D., Xia, R., Alfaro-Almagro, F., Ames, D., Amin, N., Amouyel, P., Beiser, A.S., Brodaty, H., Deary, I.J., Fennema-Notestine, C., Gampawar, P.G., Gottesman, R., Griffanti, L., Jack, C.R., Jenkinson, M., Jiang, J., Kral, B.G., Kwok, J.B., Lampe, L., Liewald, D.C.M., Maillard, P., Marchini, J., Bastin, M.E., Mazoyer, B., Pirpamer, L., Romero, J.R., Roshchupkin, G.V., Schofield, P.R., Schroeter, M.L., Stott, D.J., Thalamuthu, A., Trollor, J., Tzourio, C., Van der Grond, J., Vernooij, M.W., Witte, V.A., Wright, M.J., Yang, Q., Morris, Z., Siggurdsson, S., Psaty, B.M., Villringer, A., Schmidt, H., Håberg, A.K., van Duijn, C.M., Jukema, J.W., Dichgans, M., Sacco, R.L., Wright, C.B., Kremen, W.S., Becker, L.C., Thompson, P.M., Mosley, T.H., Wardlaw, J.M., Ikram, M.A., Adams, H.H.H., Seshadri, S., Sachdev, P.S., Smith, S.M., Launer, L., Longstreth, W.T., DeCarli, C., Schmidt, R., Fornage, M., Debette, S., Nyquist, P.A., Armstrong, N.J., Mather, K.A., Sargurupremraj, M., Knol, M.J., Malik, R., Satizabal, C.L., Yanek, L.R., Wen, W., Gudnason, V.G., Dueker, N.D., Elliott, L.T., Hofer, E., Bis, J., Jahanshad, N., Li, S., Logue, M.A., Luciano, M., Scholz, M., Smith, A.V., Trompet, S., Vojinovic, D., Xia, R., Alfaro-Almagro, F., Ames, D., Amin, N., Amouyel, P., Beiser, A.S., Brodaty, H., Deary, I.J., Fennema-Notestine, C., Gampawar, P.G., Gottesman, R., Griffanti, L., Jack, C.R., Jenkinson, M., Jiang, J., Kral, B.G., Kwok, J.B., Lampe, L., Liewald, D.C.M., Maillard, P., Marchini, J., Bastin, M.E., Mazoyer, B., Pirpamer, L., Romero, J.R., Roshchupkin, G.V., Schofield, P.R., Schroeter, M.L., Stott, D.J., Thalamuthu, A., Trollor, J., Tzourio, C., Van der Grond, J., Vernooij, M.W., Witte, V.A., Wright, M.J., Yang, Q., Morris, Z., Siggurdsson, S., Psaty, B.M., Villringer, A., Schmidt, H., Håberg, A.K., van Duijn, C.M., Jukema, J.W., Dichgans, M., Sacco, R.L., Wright, C.B., Kremen, W.S., Becker, L.C., Thompson, P.M., Mosley, T.H., Wardlaw, J.M., Ikram, M.A., Adams, H.H.H., Seshadri, S., Sachdev, P.S., Smith, S.M., Launer, L., Longstreth, W.T., DeCarli, C., Schmidt, R., Fornage, M., Debette, S., and Nyquist, P.A.
Abstract: Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was mo
Published: 2020

40. Global and regional development of the human cerebral cortex: Molecular architecture and occupational aptitudes

Author: Paus, T., Seshadri, S., Pausova, Z., Sestan, N., Jahanshad, N., Ding, L., Kremen, W.S., Franz, C.E., Gillespie, N.A., Debette, S., Maingault, S., Mishra, A., Tzourio, C., Grabe, H.J., Bülow, R., Wittfeld, K., van der -Palitschka, S., Frenzel, S., Ikram, M.A., Adams, H.H.H.H., Evans, T.E., Terzikhan, N., Sachdev, P.S., Wen, W., Brodaty, H., Wright, M.J., Trollor, J.N., Thalamuthu, A., Schofield, P.R., Kwok, J.B., Jiang, J., Ames, D., Mather, K.A., Armstrong, N.J., Villringer, A., Beyer, F., Witte, A.V., Loeffler, M., Scholz, M., Deary, I.E., Wardlaw, J.M., Harris, M.A., Bastin, M.E., Lewis, L., Karama, S., Luciano, M., Yang, Q., Li, S., Bis, J.C., Mazoyer, B., Crivello, F., Carrion-Castillo, A., Schmidt, H., Schmidt, R., Pirpamer, L., Saba, Y., Fornage, M., Mosley, T.H., Gottesman, R., Jian, X., Sousa, A.M.M., Roshchupkin, G.V., Tilley, S., Vosberg, D.E., Patel, Y., Hofer, E., Ma, S., Shin, J., Paus, T., Seshadri, S., Pausova, Z., Sestan, N., Jahanshad, N., Ding, L., Kremen, W.S., Franz, C.E., Gillespie, N.A., Debette, S., Maingault, S., Mishra, A., Tzourio, C., Grabe, H.J., Bülow, R., Wittfeld, K., van der -Palitschka, S., Frenzel, S., Ikram, M.A., Adams, H.H.H.H., Evans, T.E., Terzikhan, N., Sachdev, P.S., Wen, W., Brodaty, H., Wright, M.J., Trollor, J.N., Thalamuthu, A., Schofield, P.R., Kwok, J.B., Jiang, J., Ames, D., Mather, K.A., Armstrong, N.J., Villringer, A., Beyer, F., Witte, A.V., Loeffler, M., Scholz, M., Deary, I.E., Wardlaw, J.M., Harris, M.A., Bastin, M.E., Lewis, L., Karama, S., Luciano, M., Yang, Q., Li, S., Bis, J.C., Mazoyer, B., Crivello, F., Carrion-Castillo, A., Schmidt, H., Schmidt, R., Pirpamer, L., Saba, Y., Fornage, M., Mosley, T.H., Gottesman, R., Jian, X., Sousa, A.M.M., Roshchupkin, G.V., Tilley, S., Vosberg, D.E., Patel, Y., Hofer, E., Ma, S., and Shin, J.
Abstract: We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade—albeit in a very limited manner—to behaviors as complex as the choice of one’s occupation.
Published: 2020

41. The genetic architecture of the human cerebral cortex

Author: Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., Medland, S.E., Grasby, K.L., Jahanshad, N., Painter, J.N., Colodro-Conde, L., Bralten, J., Hibar, D.P., Lind, P.A., Pizzagalli, F., Ching, C.R.K., McMahon, M.A.B., Shatokhina, N., Zsembik, L.C.P., Thomopoulos, S.I., Zhu, A.H., Strike, L.T., Agartz, I., Alhusaini, S., Almeida, M.A.A., Alnæs, D., Amlien, I.K., Andersson, M., Ard, T., Armstrong, N.J., Ashley-Koch, A., Atkins, J.R., Bernard, M., Brouwer, R.M., Buimer, E.E.L., Bülow, R., Bürger, C., Cannon, D.M., Chakravarty, M.M., Chen, Q., Cheung, J.W., Couvy-Duchesne, B., Dale, A.M., Dalvie, S., de Araujo, T.K., de Zubicaray, G.I., de Zwarte, S.M.C., den Braber, A., Doan, N.T., Dohm, K., Ehrlich, S., Engelbrecht, H-R, Erk, S., Fan, C.C., Fedko, I.O., Foley, S.F., Ford, J.M., Fukunaga, M., Garrett, M.E., Ge, T., Giddaluru, S., Goldman, A.L., Green, M.J., Groenewold, N.A., Grotegerd, D., Gurholt, T.P., Gutman, B.A., Hansell, N.K., Harris, M.A., Harrison, M.B., Haswell, C.C., Hauser, M., Herms, S., Heslenfeld, D.J., Ho, N.F., Hoehn, D., Hoffmann, P., Holleran, L., Hoogman, M., Hottenga, J-J, Ikeda, M., Janowitz, D., Jansen, I.E., Jia, T., Jockwitz, C., Kanai, R., Karama, S., Kasperaviciute, D., Kaufmann, T., Kelly, S., Kikuchi, M., Klein, M., Knapp, M., Knodt, A.R., Krämer, B., Lam, M., Lancaster, T.M., Lee, P.H., Lett, T.A., Lewis, L.B., Lopes-Cendes, I., Luciano, M., Macciardi, F., Marquand, A.F., Mathias, S.R., Melzer, T.R., Milaneschi, Y., Mirza-Schreiber, N., Moreira, J.C.V., Mühleisen, T.W., Müller-Myhsok, B., Najt, P., Nakahara, S., Nho, K., Olde Loohuis, L.M., Orfanos, D.P., Pearson, J.F., Pitcher, T.L., Pütz, B., Quidé, Y., Ragothaman, A., Rashid, F.M., Reay, W.R., Redlich, R., Reinbold, C.S., Repple, J., Richard, G., Riedel, B.C., Risacher, S.L., Rocha, C.S., Mota, N.R., Salminen, L., Saremi, A., Saykin, A.J., Schlag, F., Schmaal, L., Schofield, P.R., Secolin, R., Shapland, C.Y., Shen, L., Shin, J., Shumskaya, E., Sønderby, I.E., Sprooten, E., Tansey, K.E., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Turner, J.A., Uhlmann, A., Vallerga, C.L., van der Meer, D., van Donkelaar, M.M.J., van Eijk, L., Van Erp, T.G.M., van Haren, N.E.M., Van Rooij, D., van Tol, M-J, Veldink, J.H., Verhoef, E., Walton, E., Wang, M., Wang, Y., Wardlaw, J.M., Wen, W., Westlye, L.T., Whelan, C.D., Witt, S.H., Wittfeld, K., Wolf, C., Wolfers, T., Wu, J.Q., Yasuda, C.L., Zaremba, D., Zhang, Z., Zwiers, M.P., Artiges, E., Assareh, A.A., Ayesa-Arriola, R., Belger, A., Brandt, C.L., Brown, G.G., Cichon, S., Curran, J.E., Davies, G.E., Degenhardt, F., Dennis, M.F., Dietsche, B., Djurovic, S., Doherty, C.P., Espiritu, R., Garijo, D., Gil, Y., Gowland, P.A., Green, R.C., Häusler, A.N., Heindel, W., Ho, B-C., Hoffmann, W.U., Holsboer, F., Homuth, G., Hosten, N., Jack, C.R., Jang, M., Jansen, A., Kimbrel, N.A., Kolskår, K., Koops, S., Krug, A., Lim, K.O., Luykx, J.J., Mathalon, D.H., Mather, K.A., Mattay, V.S., Matthews, S., Mayoral Van Son, J., McEwen, S.C., Melle, I., Morris, D.W., Mueller, B.A., Nauck, M., Nordvik, J.E., Nöthen, M.M., O’Leary, D.S., Opel, N., Martinot, M-L.P., Pike, G.B., Preda, A., Quinlan, E.B., Rasser, P.E., Ratnakar, V., Reppermund, S., Steen, V.M., Tooney, P.A., Torres, F.R., Veltman, D.J., Voyvodic, J.T., Whelan, R., White, T., Yamamori, H., Adams, H.H.H., Bis, J.C., Debette, S., DeCarli, C., Fornage, M., Gudnason, V., Hofer, E., Ikram, M.A., Launer, L., Longstreth, W.T., Lopez, O.L., Mazoyer, B., Mosley, T.H., Roshchupkin, G.V., Satizabal, C.L., Schmidt, R., Seshadri, S., Yang, Q., Alvim, M.K.M., Ames, D., Anderson, T.J., Andreassen, O.A., Arias-Vasquez, A., Bastin, M.E., Baune, B.T., Beckham, J.C., Blangero, J., Boomsma, D.I., Brodaty, H., Brunner, H.G., Buckner, R.L., Buitelaar, J.K., Bustillo, J.R., Cahn, W., Cairns, M.J., Calhoun, V., Carr, V.J., Caseras, X., Caspers, S., Cavalleri, G.L., Cendes, F., Corvin, A., Crespo-Facorro, B., Dalrymple-Alford, J.C., Dannlowski, U., de Geus, E.J.C., Deary, I.J., Delanty, N., Depondt, C., Desrivières, S., Donohoe, G., Espeseth, T., Fernández, G., Fisher, S.E., Flor, H., Forstner, A.J., Francks, C., Franke, B., Glahn, D.C., Gollub, R.L., Grabe, H.J., Gruber, O., Håberg, A.K., Hariri, A.R., Hartman, C.A., Hashimoto, R., Heinz, A., Henskens, F.A., Hillegers, M.H.J., Hoekstra, P.J., Holmes, A.J., Hong, L.E., Hopkins, W.D., Hulshoff Pol, H.E., Jernigan, T.L., Jönsson, E.G., Kahn, R.S., Kennedy, M.A., Kircher, T.T.J., Kochunov, P., Kwok, J.B.J., Le Hellard, S., Loughland, C.M., Martin, N.G., Martinot, J-L, McDonald, C., McMahon, K.L., Meyer-Lindenberg, A., Michie, P.T., Morey, R.A., Mowry, B., Nyberg, L., Oosterlaan, J., Ophoff, R.A., Pantelis, C., Paus, T., Pausova, Z., Penninx, B.W.J.H., Polderman, T.J.C., Posthuma, D., Rietschel, M., Roffman, J.L., Rowland, L.M., Sachdev, P.S., Sämann, P.G., Schall, U., Schumann, G., Scott, R.J., Sim, K., Sisodiya, S.M., Smoller, J.W., Sommer, I.E., St Pourcain, B., Stein, D.J., Toga, A.W., Trollor, J.N., van der Wee, N.J.A., van ’t Ent, D., Völzke, H., Walter, H., Weber, B., Weinberger, D.R., Wright, M.J., Zhou, J., Stein, J.L., Thompson, P.M., and Medland, S.E.
Abstract: INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When co
Published: 2020

42. Significant out-of-sample classification from methylation profile scoring for amyotrophic lateral sclerosis

Author: Nabais, M.F., Lin, T., Benyamin, B., Williams, K.L., Garton, F.C., Vinkhuyzen, A.A.E., Zhang, F., Vallerga, C.L., Restuadi, R., Freydenzon, A., Zwamborn, R.A.J., Hop, P.J., Robinson, M.R., Gratten, J., Visscher, P.M., Hannon, E., Mill, J., Brown, M.A., Laing, N.G., Mather, K.A., Sachdev, P.S., Ngoh, S.T., Steyn, F.J., Wallace, L., Henders, A.K., Needham, M., Veldink, J.H., Mathers, S., Nicholson, G., Rowe, D.B., Henderson, R.D., McCombe, P.A., Pamphlett, R., Yang, J., Blair, I.P., McRae, A.F., Wray, N.R., Nabais, M.F., Lin, T., Benyamin, B., Williams, K.L., Garton, F.C., Vinkhuyzen, A.A.E., Zhang, F., Vallerga, C.L., Restuadi, R., Freydenzon, A., Zwamborn, R.A.J., Hop, P.J., Robinson, M.R., Gratten, J., Visscher, P.M., Hannon, E., Mill, J., Brown, M.A., Laing, N.G., Mather, K.A., Sachdev, P.S., Ngoh, S.T., Steyn, F.J., Wallace, L., Henders, A.K., Needham, M., Veldink, J.H., Mathers, S., Nicholson, G., Rowe, D.B., Henderson, R.D., McCombe, P.A., Pamphlett, R., Yang, J., Blair, I.P., McRae, A.F., and Wray, N.R.
Abstract: We conducted DNA methylation association analyses using Illumina 450K data from whole blood for an Australian amyotrophic lateral sclerosis (ALS) case–control cohort (782 cases and 613 controls). Analyses used mixed linear models as implemented in the OSCA software. We found a significantly higher proportion of neutrophils in cases compared to controls which replicated in an independent cohort from the Netherlands (1159 cases and 637 controls). The OSCA MOMENT linear mixed model has been shown in simulations to best account for confounders. When combined in a methylation profile score, the 25 most-associated probes identified by MOMENT significantly classified case–control status in the Netherlands sample (area under the curve, AUC = 0.65, CI95% = [0.62–0.68], p = 8.3 × 10−22). The maximum AUC achieved was 0.69 (CI95% = [0.66–0.71], p = 4.3 × 10−34) when cell-type proportion was included in the predictor.
Published: 2020

43. Age-Related changes of Peak Width Skeletonized Mean Diffusivity (PSMD) across the adult lifespan: A Multi-Cohort Study

Author: Beaudet, G., Tsuchida, A., Petit, L., Tzourio, C., Caspers, S., Schreiber, J., Pausova, Z., Patel, Y., Paus, T., Schmidt, R., Pirpamer, L., Sachdev, P.S., Brodaty, H., Kochan, N., Trollor, J., Wen, W., Armstrong, N.J., Deary, I.J., Bastin, M.E., Wardlaw, J.M., Munoz Maniega, S., Witte, A.V., Villringer, A., Duering, M., Debette, S., Mazoyer, B., Beaudet, G., Tsuchida, A., Petit, L., Tzourio, C., Caspers, S., Schreiber, J., Pausova, Z., Patel, Y., Paus, T., Schmidt, R., Pirpamer, L., Sachdev, P.S., Brodaty, H., Kochan, N., Trollor, J., Wen, W., Armstrong, N.J., Deary, I.J., Bastin, M.E., Wardlaw, J.M., Munoz Maniega, S., Witte, A.V., Villringer, A., Duering, M., Debette, S., and Mazoyer, B.
Abstract: Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant incre
Published: 2020

44. Hippocampal size and dementia in stroke patients: The Sydney stroke study

Author: Sachdev, P.S., Chen, X., Joscelyne, A., Wen, W., Altendorf, A., and Brodaty, H.
Published: 2007
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45. White matter hyperintensities are related to physical disability and poor motor function

Author: Sachdev, P.S., Wen, W., Christensen, H., and Jorm, A.F.
Subjects: Motor ability -- Evaluation, Cognition -- Evaluation, Cognition -- Physiological aspects, Health -- Evaluation, Brain -- Abnormalities, Brain -- Evaluation, Health, Psychology and mental health
Published: 2005

46. 1H MRS in stroke patients with and without cognitive impairment

Author: Ross, A.J., Sachdev, P.S., Wen, W., Valenzuela, M.J., and Brodaty, H.
Published: 2005
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47. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018)

Author: Davies, G., Lam, M., Harris, S.E., Trampush, J.W., Luciano, M., Hill, W.D., Hagenaars, S.P., Ritchie, S.J., Marioni, R.E., Fawns-Ritchie, C., Liewald, D.C.M., Okely, J.A., Ahola-Olli, A.V., Barnes, C.L.K., Bertram, L., Bis, J.C., Burdick, K.E., Christoforou, A., DeRosse, P., Djurovic, S., Espeseth, T., Giakoumaki, S., Giddaluru, S., Gustavson, D.E., Hayward, C., Hofer, E., Ikram, M.A., Karlsson, R., Knowles, E., Lahti, J., Leber, M., Li, S., Mather, K.A., Melle, I., Morris, D., Oldmeadow, C., Palviainen, T., Payton, A., Pazoki, R., Petrovic, K., Reynolds, C.A., Sargurupremraj, M., Scholz, M., Smith, J.A., Smith, A.V., Terzikhan, N., Thalamuthu, A., Trompet, S., Lee, S.J. van der, Ware, E.B., Windham, B.G., Wright, M.J., Yang, J.Y., Yu, J., Ames, D., Amin, N., Amouyel, P., Andreassen, O.A., Armstrong, N.J., Assareh, A.A., Attia, J.R., Attix, D., Avramopoulos, D., Bennett, D.A., Bohmer, A.C., Boyle, P.A., Brodaty, H., Campbell, H., Cannon, T.D., Cirulli, E.T., Congdon, E., Conley, E.D., Corley, J., Cox, S.R., Dale, A.M., Dehghan, A., Dick, D., Dickinson, D., Eriksson, J.G., Evangelou, E., Faul, J.D., Ford, I., Freimer, N.A., Gao, H., Giegling, I., Gillespie, N.A., Gordon, S.D., Gottesman, R.F., Griswold, M.E., Gudnason, V., Harris, T.B., Hartmann, A.M., Hatzimanolis, A., Heiss, G., Holliday, E.G., Joshi, P.K., Kahonen, M., Kardia, S.L.R., Karlsson, I., Kleineidam, L., Knopman, D.S., Kochan, N.A., Konte, B., Kwok, J.B., Hellard, S. le, Lee, T., Lehtimaki, T., Li, S.C., Lill, C.M., Liu, T., Koini, M., London, E., Longstreth, W.T., Lopez, O.L., Loukola, A., Luck, T., Lundervold, A.J., Lundquist, A., Lyytikainen, L.P., Martin, N.G., Montgomery, G.W., Murray, A.D., Need, A.C., Noordam, R., Nyberg, L., Ollier, W., Papenberg, G., Pattie, A., Polasek, O., Poldrack, R.A., Psaty, B.M., Reppermund, S., Riedel-Heller, S.G., Rose, R.J., Rotter, J.I., Roussos, P., Rovio, S.P., Saba, Y., Sabb, F.W., Sachdev, P.S., Satizabal, C.L., Schmid, M., Scott, R.J., Scult, M.A., Simino, J., Slagboom, P.E., Smyrnis, N., Soumare, A., Stefanis, N.C., Stott, D.J., Straub, R.E., Sundet, K., Taylor, A.M., Taylor, K.D., Tzoulaki, I., Tzourio, C., Uitterlinden, A., Vitart, V., Voineskos, A.N., Kaprio, J., Wagner, M., Wagner, H., Weinhold, L., Wen, K.H., Widen, E., Yang, Q., Zhao, W., Adams, H.H.H., Arking, D.E., Bilder, R.M., Bitsios, P., Boerwinkle, E., Chiba-Falek, O., Corvin, A., Jager, P.L. de, Debette, S., Donohoe, G., Elliott, P., Fitzpatrick, A.L., Gill, M., Glahn, D.C., Hagg, S., Hansell, N.K., Hariri, A.R., Ikram, M.K., Jukema, J.W., Vuoksimaa, E., Keller, M.C., Kremen, W.S., Launer, L., Lindenberger, U., Palotie, A., Pedersen, N.L., Pendleton, N., Porteous, D.J., Raikkonen, K., Raitakari, O.T., Ramirez, A., Reinvang, I., Rudan, I., Rujescu, D., Schmidt, R., Schmidt, H., Schofield, P.W., Schofield, P.R., Starr, J.M., Steen, V.M., Trollor, J.N., Turner, S.T., Duijn, C.M. van, Villringer, A., Weinberger, D.R., Weir, D.R., Wilson, J.F., Malhotra, A., McIntosh, A.M., Gale, C.R., Seshadri, S., Mosley, T.H., Bressler, J., Lencz, T., and Deary, I.J.
Published: 2019

48. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting

Author: Chauhan, G., Adams, H.H.H., Satizabal, C.L., Bis, J.C., Teumer, A., Sargurupremraj, M., Hofer, E., Trompet, S., Hilal, S., Smith, A.V., Jian, X.Q., Malik, R., Traylor, M., Pulit, S.L., Amouyel, P., Mazoyer, B., Zhu, Y.C., Kaffashian, S., Schilling, S., Beecham, G.W., Montine, T.J., Schellenberg, G.D., Kjartansson, O., Gudnason, V., Knopman, D.S., Griswold, M.E., Windham, B.G., Gottesman, R.F., Mosley, T.H., Schmidt, R., Saba, Y., Schmidt, H., Takeuchi, F., Yamaguchi, S., Nabika, T., Kato, N., Rajan, K.B., Aggarwal, N.T., Jager, P.L. de, Evans, D.A., Psaty, B.M., Rotter, J.I., Rice, K., Lopez, O.L., Liao, J.M., Chen, C., Cheng, C.Y., Wong, T.Y., Ikram, M.K., Lee, S.J. van der, Amin, N., Chouraki, V., DeStefano, A.L., Aparicio, H.J., Romero, J.R., Maillard, P., DeCarli, C., Wardlaw, J.M., Hernandez, M.D.V., Luciano, M., Liewald, D., Deary, I.J., Starr, J.M., Bastin, M.E., Maniega, S.M., Slagboom, P.E., Beekman, M., Deelen, J., Uh, H.W., Lemmens, R., Brodaty, H., Wright, M.J., Ames, D., Boncoraglio, G.B., Hopewell, J.C., Beecham, A.H., Blanton, S.H., Wright, C.B., Sacco, R.L., Wen, W., Thalamuthu, A., Armstrong, N.J., Chong, E., Schofield, P.R., Kwok, J.B., Grond, J. van der, Stott, D.J., Ford, I., Jukema, J.W., Vernooij, M.W., Hofman, A., Uitterlinden, A.G., Lugt, A. van der, Wittfeld, K., Grabe, H.J., Hosten, N., Sarnowski, B. von, Volker, U., Levi, C., Jimenez-Conde, J., Sharma, P., Sudlow, C.L.M., Rosand, J., Woo, D., Cole, J.W., Meschia, J.F., Slowik, A., Thijs, V., Lindgren, A., Melander, O., Grewal, R.P., Rundek, T., Rexrode, K., Rothwell, P.M., Arnett, D.K., Jern, C., Johnson, J.A., Benavente, O.R., Wasssertheil-Smoller, S., Lee, J.M., Wong, Q., Mitchell, B.D., Rich, S.S., McArdle, P.F., Geerlings, M.I., Graaf, Y. van der, Bakker, P.I.W. de, Asselbergs, F.W., Srikanth, V., Thomson, R., McWhirter, R., Moran, C., Callisaya, M., Phan, T., Rutten-Jacobs, L.C.A., Bevan, S., Tzourio, C., Mather, K.A., Sachdev, P.S., Duijn, C.M. van, Worrall, B.B., Dichgans, M., Kittner, S.J., Markus, H.S., Ikram, M.A., Fornage, M., Launer, L.J., Seshadri, S., Longstreth, W.T., Debette, S., Stroke Genetics Network SiGN, ISGC, METASTROKE, ADGC, and CHARGE Consortium
Subjects: Meta-analysis, Mendelian Randomization, Blood Pressure, Polymorphisms, Genome-wide Association, Silent, Insights, Small Vessel Disease, Matter Hyperintensity Volume, Ischemic Stroke, Doenças Cardio e Cérebro-vasculares
Abstract: Collaborators (845): Astrid M. Vicente Free PMC article:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369905/ Objective: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. Methods: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. Results: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. Conclusion: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI. info:eu-repo/semantics/publishedVersion
Published: 2019

49. Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017 (The Lancet (2018) 392(10159) (1923–1994), (S0140673618322256), (10.1016/S0140-6736(18)32225-6))

Author: Stanaway, J.D. Afshin, A. Gakidou, E. Lim, S.S. Abate, D. Abate, K.H. Abbafati, C. Abbasi, N. Abbastabar, H. Abd-Allah, F. Abdela, J. Abdelalim, A. Abdollahpour, I. Abdulkader, R.S. Abebe, M. Abebe, Z. Abera, S.F. Abil, O.Z. Abraha, H.N. Abrham, A.R. Abu-Raddad, L.J. Abu-Rmeileh, N.M.E. Accrombessi, M.M.K. Acharya, D. Acharya, P. Adamu, A.A. Adane, A.A. Adebayo, O.M. Adedoyin, R.A. Adekanmbi, V. Ademi, Z. Adetokunboh, O.O. Adib, M.G. Admasie, A. Adsuar, J.C. Afanvi, K.A. Afarideh, M. Agarwal, G. Aggarwal, A. Aghayan, S.A. Agrawal, A. Agrawal, S. Ahmadi, A. Ahmadi, M. Ahmadieh, H. Ahmed, M.B. Aichour, A.N. Aichour, I. Aichour, M.T.E. Akbari, M.E. Akinyemiju, T. Akseer, N. Al-Aly, Z. Al-Eyadhy, A. Al-Mekhlafi, H.M. Alahdab, F. Alam, K. Alam, S. Alam, T. Alashi, A. Alavian, S.M. Alene, K.A. Ali, K. Ali, S.M. Alijanzadeh, M. Alizadeh-Navaei, R. Aljunid, S.M. Alkerwi, A. Alla, F. Alsharif, U. Altirkawi, K. Alvis-Guzman, N. Amare, A.T. Ammar, W. Anber, N.H. Anderson, J.A. Andrei, C.L. Androudi, S. Animut, M.D. Anjomshoa, M. Ansha, M.G. Antó, J.M. Antonio, C.A.T. Anwari, P. Appiah, L.T. Appiah, S.C.Y. Arabloo, J. Aremu, O. Ärnlöv, J. Artaman, A. Aryal, K.K. Asayesh, H. Ataro, Z. Ausloos, M. Avokpaho, E.F.G.A. Awasthi, A. Ayala Quintanilla, B.P. Ayer, R. Ayuk, T.B. Azzopardi, P.S. Babazadeh, A. Badali, H. Badawi, A. Balakrishnan, K. Bali, A.G. Ball, K. Ballew, S.H. Banach, M. Banoub, J.A.M. Barac, A. Barker-Collo, S.L. Bärnighausen, T.W. Barrero, L.H. Basu, S. Baune, B.T. Bazargan-Hejazi, S. Bedi, N. Beghi, E. Behzadifar, M. Behzadifar, M. Béjot, Y. Bekele, B.B. Bekru, E.T. Belay, E. Belay, Y.A. Bell, M.L. Bello, A.K. Bennett, D.A. Bensenor, I.M. Bergeron, G. Berhane, A. Bernabe, E. Bernstein, R.S. Beuran, M. Beyranvand, T. Bhala, N. Bhalla, A. Bhattarai, S. Bhutta, Z.A. Biadgo, B. Bijani, A. Bikbov, B. Bilano, V. Bililign, N. Bin Sayeed, M.S. Bisanzio, D. Biswas, T. Bjørge, T. Blacker, B.F. Bleyer, A. Borschmann, R. Bou-Orm, I.R. Boufous, S. Bourne, R. Brady, O.J. Brauer, M. Brazinova, A. Breitborde, N.J.K. Brenner, H. Briko, A.N. Britton, G. Brugha, T. Buchbinder, R. Burnett, R.T. Busse, R. Butt, Z.A. Cahill, L.E. Cahuana-Hurtado, L. Campos-Nonato, I.R. Cárdenas, R. Carreras, G. Carrero, J.J. Carvalho, F. Castañeda-Orjuela, C.A. Castillo Rivas, J. Castro, F. Catalá-López, F. Causey, K. Cercy, K.M. Cerin, E. Chaiah, Y. Chang, H.-Y. Chang, J.-C. Chang, K.-L. Charlson, F.J. Chattopadhyay, A. Chattu, V.K. Chee, M.L. Cheng, C.-Y. Chew, A. Chiang, P.P.-C. Chimed-Ochir, O. Chin, K.L. Chitheer, A. Choi, J.-Y.J. Chowdhury, R. Christensen, H. Christopher, D.J. Chung, S.-C. Cicuttini, F.M. Cirillo, M. Cohen, A.J. Collado-Mateo, D. Cooper, C. Cooper, O.R. Coresh, J. Cornaby, L. Cortesi, P.A. Cortinovis, M. Costa, M. Cousin, E. Criqui, M.H. Cromwell, E.A. Cundiff, D.K. Daba, A.K. Dachew, B.A. Dadi, A.F. Damasceno, A.A.M. Dandona, L. Dandona, R. Darby, S.C. Dargan, P.I. Daryani, A. Das Gupta, R. Das Neves, J. Dasa, T.T. Dash, A.P. Davitoiu, D.V. Davletov, K. De la Cruz-Góngora, V. De La Hoz, F.P. De Leo, D. De Neve, J.-W. Degenhardt, L. Deiparine, S. Dellavalle, R.P. Demoz, G.T. Denova-Gutiérrez, E. Deribe, K. Dervenis, N. Deshpande, A. Des Jarlais, D.C. Dessie, G.A. Deveber, G.A. Dey, S. Dharmaratne, S.D. Dhimal, M. Dinberu, M.T. Ding, E.L. Diro, H.D. Djalalinia, S. Do, H.P. Dokova, K. Doku, D.T. Doyle, K.E. Driscoll, T.R. Dubey, M. Dubljanin, E. Duken, E.E. Duncan, B.B. Duraes, A.R. Ebert, N. Ebrahimi, H. Ebrahimpour, S. Edvardsson, D. Effiong, A. Eggen, A.E. El Bcheraoui, C. El-Khatib, Z. Elyazar, I.R. Enayati, A. Endries, A.Y. Er, B. Erskine, H.E. Eskandarieh, S. Esteghamati, A. Estep, K. Fakhim, H. Faramarzi, M. Fareed, M. Farid, T.A. Sá Farinha, C.S.E. Farioli, A. Faro, A. Farvid, M.S. Farzaei, M.H. Fatima, B. Fay, K.A. Fazaeli, A.A. Feigin, V.L. Feigl, A.B. Fereshtehnejad, S.-M. Fernandes, E. Fernandes, J.C. Ferrara, G. Ferrari, A.J. Ferreira, M.L. Filip, I. Finger, J.D. Fischer, F. Foigt, N.A. Foreman, K.J. Fukumoto, T. Fullman, N. Fürst, T. Furtado, J.M. Futran, N.D. Gall, S. Gallus, S. Gamkrelidze, A. Ganji, M. Garcia-Basteiro, A.L. Gardner, W.M. Gebre, A.K. Gebremedhin, A.T. Gebremichael, T.G. Gelano, T.F. Geleijnse, J.M. Geramo, Y.C.D. Gething, P.W. Gezae, K.E. Ghadimi, R. Ghadiri, K. Ghasemi Falavarjani, K.G. Ghasemi-Kasman, M. Ghimire, M. Ghosh, R. Ghoshal, A.G. Giampaoli, S. Gill, P.S. Gill, T.K. Gillum, R.F. Ginawi, I.A. Giussani, G. Gnedovskaya, E.V. Godwin, W.W. Goli, S. Gómez-Dantés, H. Gona, P.N. Gopalani, S.V. Goulart, A.C. Grada, A. Grams, M.E. Grosso, G. Gugnani, H.C. Guo, Y. Gupta, R. Gupta, R. Gupta, T. Gutiérrez, R.A. Gutiérrez-Torres, D.S. Haagsma, J.A. Habtewold, T.D. Hachinski, V. Hafezi-Nejad, N. Hagos, T.B. Hailegiyorgis, T.T. Hailu, G.B. Haj-Mirzaian, A. Haj-Mirzaian, A. Hamadeh, R.R. Hamidi, S. Handal, A.J. Hankey, G.J. Hao, Y. Harb, H.L. Harikrishnan, S. Haro, J.M. Hassankhani, H. Hassen, H.Y. Havmoeller, R. Hawley, C.N. Hay, S.I. Hedayatizadeh-Omran, A. Heibati, B. Heidari, B. Heidari, M. Hendrie, D. Henok, A. Heredia-Pi, I. Herteliu, C. Heydarpour, F. Heydarpour, S. Hibstu, D.T. Higazi, T.B. Hilawe, E.H. Hoek, H.W. Hoffman, H.J. Hole, M.K. Homaie Rad, E. Hoogar, P. Hosgood, H.D. Hosseini, S.M. Hosseinzadeh, M. Hostiuc, M. Hostiuc, S. Hoy, D.G. Hsairi, M. Hsiao, T. Hu, G. Hu, H. Huang, J.J. Hussen, M.A. Huynh, C.K. Iburg, K.M. Ikeda, N. Ilesanmi, O.S. Iqbal, U. Irvani, S.S.N. Irvine, C.M.S. Islam, S.M.S. Islami, F. Jackson, M.D. Jacobsen, K.H. Jahangiry, L. Jahanmehr, N. Jain, S.K. Jakovljevic, M. James, S.L. Jassal, S.K. Jayatilleke, A.U. Jeemon, P. Jha, R.P. Jha, V. Ji, J.S. Jonas, J.B. Jonnagaddala, J. Jorjoran Shushtari, Z.J. Joshi, A. Jozwiak, J.J. Jürisson, M. Kabir, Z. Kahsay, A. Kalani, R. Kanchan, T. Kant, S. Kar, C. Karami, M. Karami Matin, B.K. Karch, A. Karema, C. Karimi, N. Karimi, S.M. Kasaeian, A. Kassa, D.H. Kassa, G.M. Kassa, T.D. Kassebaum, N.J. Katikireddi, S.V. Kaul, A. Kawakami, N. Kazemi, Z. Kazemi Karyani, A. Kefale, A.T. Keiyoro, P.N. Kemp, G.R. Kengne, A.P. Keren, A. Kesavachandran, C.N. Khader, Y.S. Khafaei, B. Khafaie, M.A. Khajavi, A. Khalid, N. Khalil, I.A. Khan, G. Khan, M.S. Khan, M.A. Khang, Y.-H. Khater, M.M. Khazaei, M. Khazaie, H. Khoja, A.T. Khosravi, A. Khosravi, M.H. Kiadaliri, A.A. Kiirithio, D.N. Kim, C.-I. Kim, D. Kim, Y.-E. Kim, Y.J. Kimokoti, R.W. Kinfu, Y. Kisa, A. Kissimova-Skarbek, K. Kivimäki, M. Knibbs, L.D. Knudsen, A.K.S. Kochhar, S. Kokubo, Y. Kolola, T. Kopec, J.A. Kosen, S. Koul, P.A. Koyanagi, A. Kravchenko, M.A. Krishan, K. Krohn, K.J. Kromhout, H. Kuate Defo, B. Kucuk Bicer, B. Kumar, G.A. Kumar, M. Kuzin, I. Kyu, H.H. Lachat, C. Lad, D.P. Lad, S.D. Lafranconi, A. Lalloo, R. Lallukka, T. Lami, F.H. Lang, J.J. Lansingh, V.C. Larson, S.L. Latifi, A. Lazarus, J.V. Lee, P.H. Leigh, J. Leili, M. Leshargie, C.T. Leung, J. Levi, M. Lewycka, S. Li, S. Li, Y. Liang, J. Liang, X. Liao, Y. Liben, M.L. Lim, L.-L. Linn, S. Liu, S. Lodha, R. Logroscino, G. Lopez, A.D. Lorkowski, S. Lotufo, P.A. Lozano, R. Lucas, T.C.D. Lunevicius, R. Ma, S. Macarayan, E.R.K. Machado, Í.E. Madotto, F. Mai, H.T. Majdan, M. Majdzadeh, R. Majeed, A. Malekzadeh, R. Malta, D.C. Mamun, A.A. Manda, A.-L. Manguerra, H. Mansournia, M.A. Mantovani, L.G. Maravilla, J.C. Marcenes, W. Marks, A. Martin, R.V. Martins, S.C.O. Martins-Melo, F.R. März, W. Marzan, M.B. Massenburg, B.B. Mathur, M.R. Mathur, P. Matsushita, K. Maulik, P.K. Mazidi, M. McAlinden, C. McGrath, J.J. McKee, M. Mehrotra, R. Mehta, K.M. Mehta, V. Meier, T. Mekonnen, F.A. Melaku, Y.A. Melese, A. Melku, M. Memiah, P.N. Memish, Z.A. Mendoza, W. Mengistu, D.T. Mensah, G.A. Mensink, G.B.M. Mereta, S.T. Meretoja, A. Meretoja, T.J. Mestrovic, T. Mezgebe, H.B. Miazgowski, B. Miazgowski, T. Millear, A.I. Miller, T.R. Miller-Petrie, M.K. Mini, G.K. Mirarefin, M. Mirica, A. Mirrakhimov, E.M. Misganaw, A.T. Mitiku, H. Moazen, B. Mohajer, B. Mohammad, K.A. Mohammadi, M. Mohammadifard, N. Mohammadnia-Afrouzi, M. Mohammed, S. Mohebi, F. Mokdad, A.H. Molokhia, M. Momeniha, F. Monasta, L. Moodley, Y. Moradi, G. Moradi-Lakeh, M. Moradinazar, M. Moraga, P. Morawska, L. Morgado-Da-Costa, J. Morrison, S.D. Moschos, M.M. Mouodi, S. Mousavi, S.M. Mozaffarian, D. Mruts, K.B. Muche, A.A. Muchie, K.F. Mueller, U.O. Muhammed, O.S. Mukhopadhyay, S. Muller, K. Musa, K.I. Mustafa, G. Nabhan, A.F. Naghavi, M. Naheed, A. Nahvijou, A. Naik, G. Naik, N. Najafi, F. Nangia, V. Nansseu, J.R. Nascimento, B.R. Neal, B. Neamati, N. Negoi, I. Negoi, R.I. Neupane, S. Newton, C.R.J. Ngunjiri, J.W. Nguyen, A.Q. Nguyen, G. Nguyen, H.T. Nguyen, H.L.T. Nguyen, H.T. Nguyen, M. Nguyen, N.B. Nichols, E. Nie, J. Ningrum, D.N.A. Nirayo, Y.L. Nishi, N. Nixon, M.R. Nojomi, M. Nomura, S. Norheim, O.F. Noroozi, M. Norrving, B. Noubiap, J.J. Nouri, H.R. Nourollahpour Shiadeh, M. Nowroozi, M.R. Nsoesie, E.O. Nyasulu, P.S. Obermeyer, C.M. Odell, C.M. Ofori-Asenso, R. Ogbo, F.A. Oh, I.-H. Oladimeji, O. Olagunju, A.T. Olagunju, T.O. Olivares, P.R. Olsen, H.E. Olusanya, B.O. Olusanya, J.O. Ong, K.L. Ong, S.K. Oren, E. Orpana, H.M. Ortiz, A. Ota, E. Otstavnov, S.S. Øverland, S. Owolabi, M.O. Mahesh, P.A. Pacella, R. Pakhare, A.P. Pakpour, A.H. Pana, A. Panda-Jonas, S. Park, E.-K. Parry, C.D.H. Parsian, H. Patel, S. Pati, S. Patil, S.T. Patle, A. Patton, G.C. Paudel, D. Paulson, K.R. Paz Ballesteros, W.C. Pearce, N. Pereira, A. Pereira, D.M. Perico, N. Pesudovs, K. Petzold, M. Pham, H.Q. Phillips, M.R. Pillay, J.D. Piradov, M.A. Pirsaheb, M. Pischon, T. Pishgar, F. Plana-Ripoll, O. Plass, D. Polinder, S. Polkinghorne, K.R. Postma, M.J. Poulton, R. Pourshams, A. Poustchi, H. Prabhakaran, D. Prakash, S. Prasad, N. Purcell, C.A. Purwar, M.B. Qorbani, M. Radfar, A. Rafay, A. Rafiei, A. Rahim, F. Rahimi, Z. Rahimi-Movaghar, A. Rahimi-Movaghar, V. Rahman, M. Rahman, M.H.U. Rahman, M.A. Rai, R.K. Rajati, F. Rajsic, S. Raju, S.B. Ram, U. Ranabhat, C.L. Ranjan, P. Rath, G.K. Rawaf, D.L. Rawaf, S. Reddy, K.S. Rehm, C.D. Rehm, J. Reiner, R.C. Reitsma, M.B. Remuzzi, G. Renzaho, A.M.N. Resnikoff, S. Reynales-Shigematsu, L.M. Rezaei, S. Ribeiro, A.L.P. Rivera, J.A. Roba, K.T. Rodríguez-Ramírez, S. Roever, L. Román, Y. Ronfani, L. Roshandel, G. Rostami, A. Roth, G.A. Rothenbacher, D. Roy, A. Rubagotti, E. Rushton, L. Sabanayagam, C. Sachdev, P.S. Saddik, B. Sadeghi, E. Saeedi Moghaddam, S. Safari, H. Safari, Y. Safari-Faramani, R. Safdarian, M. Safi, S. Safiri, S. Sagar, R. Sahebkar, A. Sahraian, M.A. Sajadi, H.S. Salam, N. Salamati, P. Saleem, Z. Salimi, Y. Salimzadeh, H. Salomon, J.A. Salvi, D.D. Salz, I. Samy, A.M. Sanabria, J. Sanchez-Niño, M.D. Sánchez-Pimienta, T.G. Sanders, T. Sang, Y. Santomauro, D.F. Santos, I.S. Santos, J.V. Santric Milicevic, M.M. Sao Jose, B.P. Sardana, M. Sarker, A.R. Sarmiento-Suárez, R. Sarrafzadegan, N. Sartorius, B. Sarvi, S. Sathian, B. Satpathy, M. Sawant, A.R. Sawhney, M. Saylan, M. Sayyah, M. Schaeffner, E. Schmidt, M.I. Schneider, I.J.C. Schöttker, B. Schutte, A.E. Schwebel, D.C. Schwendicke, F. Scott, J.G. Seedat, S. Sekerija, M. Sepanlou, S.G. Serre, M.L. Serván-Mori, E. Seyedmousavi, S. Shabaninejad, H. Shaddick, G. Shafieesabet, A. Shahbazi, M. Shaheen, A.A. Shaikh, M.A. Shamah Levy, T. Shams-Beyranvand, M. Shamsi, M. Sharafi, H. Sharafi, K. Sharif, M. Sharif-Alhoseini, M. Sharifi, H. Sharma, J. Sharma, M. Sharma, R. She, J. Sheikh, A. Shi, P. Shibuya, K. Shiferaw, M.S. Shigematsu, M. Shin, M.-J. Shiri, R. Shirkoohi, R. Shiue, I. Shokraneh, F. Shoman, H. Shrime, M.G. Shupler, M.S. Si, S. Siabani, S. Sibai, A.M. Siddiqi, T.J. Sigfusdottir, I.D. Sigurvinsdottir, R. Silva, D.A.S. Silva, J.P. Silveira, D.G.A. Singh, J.A. Singh, N.P. Singh, V. Sinha, D.N. Skiadaresi, E. Skirbekk, V. Smith, D.L. Smith, M. Sobaih, B.H. Sobhani, S. Somayaji, R. Soofi, M. Sorensen, R.J.D. Soriano, J.B. Soyiri, I.N. Spinelli, A. Sposato, L.A. Sreeramareddy, C.T. Srinivasan, V. Starodubov, V.I. Steckling, N. Stein, D.J. Stein, M.B. Stevanovic, G. Stockfelt, L. Stokes, M.A. Sturua, L. Subart, M.L. Sudaryanto, A. Sufiyan, M.B. Sulo, G. Sunguya, B.F. Sur, P.J. Sykes, B.L. Szoeke, C.E.I. Tabarés-Seisdedos, R. Tabuchi, T. Tadakamadla, S.K. Takahashi, K. Tandon, N. Tassew, S.G. Tavakkoli, M. Taveira, N. Tehrani-Banihashemi, A. Tekalign, T.G. Tekelemedhin, S.W. Tekle, M.G. Temesgen, H. Temsah, M.-H. Temsah, O. Terkawi, A.S. Tessema, B. Teweldemedhin, M. Thankappan, K.R. Theis, A. Thirunavukkarasu, S. Thomas, H.J. Thomas, M.L. Thomas, N. Thurston, G.D. Tilahun, B. Tillmann, T. To, Q.G. Tobollik, M. Tonelli, M. Topor-Madry, R. Torre, A.E. Tortajada-Girbés, M. Touvier, M. Tovani-Palone, M.R. Towbin, J.A. Tran, B.X. Tran, K.B. Truelsen, T.C. Truong, N.T. Tsadik, A.G. Tudor Car, L. Tuzcu, E.M. Tymeson, H.D. Tyrovolas, S. Ukwaja, K.N. Ullah, I. Updike, R.L. Usman, M.S. Uthman, O.A. Vaduganathan, M. Vaezi, A. Valdez, P.R. Van Donkelaar, A. Varavikova, E. Varughese, S. Vasankari, T.J. Venkateswaran, V. Venketasubramanian, N. Villafaina, S. Violante, F.S. Vladimirov, S.K. Vlassov, V. Vollset, S.E. Vos, T. Vosoughi, K. Vu, G.T. Vujcic, I.S. Wagnew, F.S. Waheed, Y. Waller, S.G. Walson, J.L. Wang, Y. Wang, Y. Wang, Y.-P. Weiderpass, E. Weintraub, R.H. Weldegebreal, F. Werdecker, A. Werkneh, A.A. West, J.J. Westerman, R. Whiteford, H.A. Widecka, J. Wijeratne, T. Winkler, A.S. Wiyeh, A.B. Wiysonge, C.S. Wolfe, C.D.A. Wong, T.Y. Wu, S. Xavier, D. Xu, G. Yadgir, S. Yadollahpour, A. Yahyazadeh Jabbari, S.H. Yamada, T. Yan, L.L. Yano, Y. Yaseri, M. Yasin, Y.J. Yeshaneh, A. Yimer, E.M. Yip, P. Yisma, E. Yonemoto, N. Yoon, S.-J. Yotebieng, M. Younis, M.Z. Yousefifard, M. Yu, C. Zaidi, Z. Zaman, S.B. Zamani, M. Zavala-Arciniega, L. Zhang, A.L. Zhang, H. Zhang, K. Zhou, M. Zimsen, S.R.M. Zodpey, S. Murray, C.J.L. GBD 2017 Risk Factor Collaborators
Abstract: Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Published: 2019

50. Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study

Author: Lipnicki, D.M. Makkar, S.R. Crawford, J.D. Thalamuthu, A. Kochan, N.A. Lima-Costa, M.F. Castro-Costa, E. Ferri, C.P. Brayne, C. Stephan, B. Llibre-Rodriguez, J.J. Llibre-Guerra, J.J. Valhuerdi-Cepero, A.J. Lipton, R.B. Katz, M.J. Derby, C.A. Ritchie, K. Ancelin, M.-L. Carrière, I. Scarmeas, N. Yannakoulia, M. Hadjigeorgiou, G.M. Lam, L. Chan, W.-C. Fung, A. Guaita, A. Vaccaro, R. Davin, A. Kim, K.W. Han, J.W. Suh, S.W. Riedel-Heller, S.G. Roehr, S. Pabst, A. van Boxtel, M. Köhler, S. Deckers, K. Ganguli, M. Jacobsen, E.P. Hughes, T.F. Anstey, K.J. Cherbuin, N. Haan, M.N. Aiello, A.E. Dang, K. Kumagai, S. Chen, T. Narazaki, K. Ng, T.P. Gao, Q. Nyunt, M.S.Z. Scazufca, M. Brodaty, H. Numbers, K. Trollor, J.N. Meguro, K. Yamaguchi, S. Ishii, H. Lobo, A. Lopez-Anton, R. Santabárbara, J. Leung, Y. Lo, J.W. Popovic, G. Sachdev, P.S. Cohort Studies of Memory in an International Consortium (COSMIC)
Abstract: Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences. © 2019 Lipnicki et al.
Published: 2019

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