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301 results on '"Hartwig, Fernando P."'

1. Empirically assessing the plausibility of unconfoundedness in observational studies

Author

Hartwig, Fernando Pires, Tilling, Kate, and Smith, George Davey

Subjects
Statistics - Methodology
Abstract

The possibility of unmeasured confounding is one of the main limitations for causal inference from observational studies. There are different methods for partially empirically assessing the plausibility of unconfoundedness. However, most currently available methods require (at least partial) assumptions about the confounding structure, which may be difficult to know in practice. In this paper we describe a simple strategy for empirically assessing the plausibility of conditional unconfoundedness (i.e., whether the candidate set of covariates suffices for confounding adjustment) which does not require any assumptions about the confounding structure, requiring instead assumptions related to temporal ordering between covariates, exposure and outcome (which can be guaranteed by design), measurement error and selection into the study. The proposed method essentially relies on testing the association between a subset of covariates (those associated with the exposure given all other covariates) and the outcome conditional on the remaining covariates and the exposure. We describe the assumptions underlying the method, provide proofs, use simulations to corroborate the theory and illustrate the method with an applied example assessing the causal effect of length-for-age measured in childhood and intelligence quotient measured in adulthood using data from the 1982 Pelotas (Brazil) birth cohort. We also discuss the implications of measurement error and some important limitations.

Published
2024

3. Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

Author

Fernández-Rhodes, Lindsay, Graff, Mariaelisa, Buchanan, Victoria L, Justice, Anne E, Highland, Heather M, Guo, Xiuqing, Zhu, Wanying, Chen, Hung-Hsin, Young, Kristin L, Adhikari, Kaustubh, Palmer, Nicholette D, Below, Jennifer E, Bradfield, Jonathan, Pereira, Alexandre C, Glover, LáShauntá, Kim, Daeeun, Lilly, Adam G, Shrestha, Poojan, Thomas, Alvin G, Zhang, Xinruo, Chen, Minhui, Chiang, Charleston WK, Pulit, Sara, Horimoto, Andrea, Krieger, Jose E, Guindo-Martínez, Marta, Preuss, Michael, Schumann, Claudia, Smit, Roelof AJ, Torres-Mejía, Gabriela, Acuña-Alonzo, Victor, Bedoya, Gabriel, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, González-José, Rolando, Poletti, Giovanni, Rothhammer, Francisco, Hakonarson, Hakon, Igo, Robert, Adler, Sharon G, Iyengar, Sudha K, Nicholas, Susanne B, Gogarten, Stephanie M, Isasi, Carmen R, Papnicolaou, George, Stilp, Adrienne M, Qi, Qibin, Kho, Minjung, Smith, Jennifer A, Langefeld, Carl D, Wagenknecht, Lynne, Mckean-Cowdin, Roberta, Gao, Xiaoyi Raymond, Nousome, Darryl, Conti, David V, Feng, Ye, Allison, Matthew A, Arzumanyan, Zorayr, Buchanan, Thomas A, Chen, Yii-Der Ida, Genter, Pauline M, Goodarzi, Mark O, Hai, Yang, Hsueh, Willa, Ipp, Eli, Kandeel, Fouad R, Lam, Kelvin, Li, Xiaohui, Nadler, Jerry L, Raffel, Leslie J, Roll, Kathryn, Sandow, Kevin, Tan, Jingyi, Taylor, Kent D, Xiang, Anny H, Yao, Jie, Audirac-Chalifour, Astride, Peralta Romero, Jose de Jesus, Hartwig, Fernando, Horta, Bernando, Blangero, John, Curran, Joanne E, Duggirala, Ravindranath, Lehman, Donna E, Puppala, Sobha, Fejerman, Laura, John, Esther M, Aguilar-Salinas, Carlos, Burtt, Noël P, Florez, Jose C, García-Ortíz, Humberto, González-Villalpando, Clicerio, Mercader, Josep, Orozco, Lorena, Tusié-Luna, Teresa, Blanco, Estela, Gahagan, Sheila, Cox, Nancy J, and Hanis, Craig

Abstract

[This corrects the article DOI: 10.1016/j.xhgg.2022.100099.].

Published
2023

4. Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.

Author

Wang, Zhe, Emmerich, Andrew, Pillon, Nicolas, Moore, Tim, Hemerich, Daiane, Cornelis, Marilyn, Mazzaferro, Eugenia, Broos, Siacia, Ahluwalia, Tarunveer, Bartz, Traci, Bentley, Amy, Bielak, Lawrence, Chong, Mike, Chu, Audrey, Berry, Diane, Dorajoo, Rajkumar, Dueker, Nicole, Kasbohm, Elisa, Feenstra, Bjarke, Feitosa, Mary, Gieger, Christian, Graff, Mariaelisa, Hall, Leanne, Haller, Toomas, Hartwig, Fernando, Hillis, David, Huikari, Ville, Heard-Costa, Nancy, Holzapfel, Christina, Jackson, Anne, Johansson, Åsa, Jørgensen, Anja, Kaakinen, Marika, Karlsson, Robert, Kerr, Kathleen, Kim, Boram, Koolhaas, Chantal, Kutalik, Zoltan, Lagou, Vasiliki, Lind, Penelope, Lorentzon, Mattias, Lyytikäinen, Leo-Pekka, Mangino, Massimo, Metzendorf, Christoph, Monroe, Kristine, Pacolet, Alexander, Pérusse, Louis, Pool, Rene, Richmond, Rebecca, Rivera, Natalia, Robiou-du-Pont, Sebastien, Schraut, Katharina, Schulz, Christina-Alexandra, Stringham, Heather, Tanaka, Toshiko, Teumer, Alexander, Turman, Constance, van der Most, Peter, Vanmunster, Mathias, van Rooij, Frank, van Vliet-Ostaptchouk, Jana, Zhang, Xiaoshuai, Zhao, Jing-Hua, Zhao, Wei, Balkhiyarova, Zhanna, Balslev-Harder, Marie, Baumeister, Sebastian, Beilby, John, Blangero, John, Boomsma, Dorret, Brage, Soren, Braund, Peter, Brody, Jennifer, Bruinenberg, Marcel, Ekelund, Ulf, Liu, Ching-Ti, Cole, John, Collins, Francis, Cupples, L, Esko, Tõnu, Enroth, Stefan, Faul, Jessica, Fernandez-Rhodes, Lindsay, Fohner, Alison, Franco, Oscar, Galesloot, Tessel, Gordon, Scott, Grarup, Niels, Hartman, Catharina, Heiss, Gerardo, Hui, Jennie, Illig, Thomas, Jago, Russell, James, Alan, Joshi, Peter, Jung, Taeyeong, Kähönen, Mika, Kilpeläinen, Tuomas, Koh, Woon-Puay, and Kolcic, Ivana

Subjects
Actinin, Cross-Sectional Studies, Exercise, Genome-Wide Association Study, Humans, Leisure Activities, Sedentary Behavior
Abstract

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Published
2022

5. A generalized definition of the average causal effect for both binary and continuous treatments

Author

Hartwig, Fernando Pires

Subjects
Statistics - Methodology
Abstract

One of the main tasks of causal inference is estimating well-defined causal parameters. One of the main causal parameters is the average causal effect (ACE) - the expected value of the individual level causal effects in the target population. For binary treatments, the individual level causal effect is defined as contrast between potential outcomes. For continuous outcomes, however, there are many such contrasts in finite samples, thus hampering their use as a useful summary of the causal relationship. Here, we proposed a generalized version of the ACE, where individual level causal effects are defined as the derivative (with respect to the treatment) of the individual level causal dose-response function evaluated at treatment value that the individual has. This definition is equivalent to the conventional definition for binary treatments, but also incorporates continuous treatments. We demonstrate that this quantity can be estimated under conventional causal assumptions and illustrate the theoretical ideas with a simulation study., Comment: The reason for withdrawal is that the proposed definition already exists in a literature that the author was unfamiliar with. More specifically, it exists in the econometrics literature under the name "average derivative effect". Therefore, although this work has been conducted independently of such previous work, it does not contribute anything new to the literature

Published
2021

6. Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits—The Hispanic/Latino Anthropometry Consortium

Author

Fernández-Rhodes, Lindsay, Graff, Mariaelisa, Buchanan, Victoria L, Justice, Anne E, Highland, Heather M, Guo, Xiuqing, Zhu, Wanying, Chen, Hung-Hsin, Young, Kristin L, Adhikari, Kaustubh, Palmer, Nicholette D, Below, Jennifer E, Bradfield, Jonathan, Pereira, Alexandre C, Glover, LáShauntá, Kim, Daeeun, Lilly, Adam G, Shrestha, Poojan, Thomas, Alvin G, Zhang, Xinruo, Chen, Minhui, Chiang, Charleston WK, Pulit, Sara, Horimoto, Andrea, Krieger, Jose E, Guindo-Martínez, Marta, Preuss, Michael, Schumann, Claudia, Smit, Roelof AJ, Torres-Mejía, Gabriela, Acuña-Alonzo, Victor, Bedoya, Gabriel, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, González-José, Rolando, Poletti, Giovanni, Rothhammer, Francisco, Hakonarson, Hakon, Igo, Robert, Adler, Sharon G, Iyengar, Sudha K, Nicholas, Susanne B, Gogarten, Stephanie M, Isasi, Carmen R, Papnicolaou, George, Stilp, Adrienne M, Qi, Qibin, Kho, Minjung, Smith, Jennifer A, Langefeld, Carl D, Wagenknecht, Lynne, Mckean-Cowdin, Roberta, Gao, Xiaoyi Raymond, Nousome, Darryl, Conti, David V, Feng, Ye, Allison, Matthew A, Arzumanyan, Zorayr, Buchanan, Thomas A, Chen, Yii-Der Ida, Genter, Pauline M, Goodarzi, Mark O, Hai, Yang, Hsueh, Willa, Ipp, Eli, Kandeel, Fouad R, Lam, Kelvin, Li, Xiaohui, Nadler, Jerry L, Raffel, Leslie J, Roll, Kathryn, Sandow, Kevin, Tan, Jingyi, Taylor, Kent D, Xiang, Anny H, Yao, Jie, Audirac-Chalifour, Astride, de Jesus Peralta Romero, Jose, Hartwig, Fernando, Horta, Bernando, Blangero, John, Curran, Joanne E, Duggirala, Ravindranath, Lehman, Donna E, Puppala, Sobha, Fejerman, Laura, John, Esther M, Aguilar-Salinas, Carlos, Burtt, Noël P, Florez, Jose C, García-Ortíz, Humberto, González-Villalpando, Clicerio, Mercader, Josep, Orozco, Lorena, Tusié-Luna, Teresa, Blanco, Estela, Gahagan, Sheila, Cox, Nancy J, and Hanis, Craig

Subjects
Biological Sciences, Genetics, Obesity, Human Genome, Hispanic/Latino, anthropometrics, diversity, fine-mapping, obesity, population stratification, trans-ancestral or trans-ethnic
Abstract

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

Published
2022

7. Homogeneity in the instrument-treatment association is not sufficient for the Wald estimand to equal the average causal effect for a binary instrument and a continuous exposure

Author

Hartwig, Fernando Pires, Wang, Linbo, Smith, George Davey, and Davies, Neil Martin

Subjects
Statistics - Methodology
Abstract

Background: Interpreting instrumental variable results often requires further assumptions in addition to the core assumptions of relevance, independence, and the exclusion restriction. Methods: We assess whether instrument-exposure additive homogeneity renders the Wald estimand equal to the average derivative effect (ADE) in the case of a binary instrument and a continuous exposure. Results: Instrument-exposure additive homogeneity is insufficient for ADE identification when the instrument is binary, the exposure is continuous and the effect of the exposure on the outcome is non-linear on the additive scale. For a binary exposure, the exposure-outcome effect is necessarily additive linear, so the homogeneity condition is sufficient. Conclusions: For binary instruments, instrument-exposure additive homogeneity identifies the ADE if the exposure is also binary. Otherwise, additional assumptions (such as additive linearity of the exposure-outcome effect) are required.

Published
2021

8. Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL

Author

Justice, Anne E, Young, Kristin, Gogarten, Stephanie M, Sofer, Tamar, Graff, Misa, Love, Shelly Ann M, Wang, Yujie, Klimentidis, Yann C, Cruz, Miguel, Guo, Xiuqing, Hartwig, Fernando, Petty, Lauren, Yao, Jie, Allison, Matthew A, Below, Jennifer E, Buchanan, Thomas A, Chen, Yii-Der Ida, Goodarzi, Mark O, Hanis, Craig, Highland, Heather M, Hsueh, Willa A, Ipp, Eli, Parra, Esteban, Palmas, Walter, Raffel, Leslie J, Rotter, Jerome I, Tan, Jingyi, Taylor, Kent D, Valladares, Adan, Xiang, Anny H, Sánchez-Johnsen, Lisa, Isasi, Carmen R, and North, Kari E

Subjects
Biological Sciences, Genetics, Nutrition, Behavioral and Social Science, Prevention, Obesity, Clinical Research, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Stroke, Metabolic and endocrine, Good Health and Well Being, Adiposity, Alleles, Body Fat Distribution, Genome-Wide Association Study, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, Medical and Health Sciences, Genetics & Heredity
Abstract

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P

Published
2021

9. Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.

Author

de Las Fuentes, Lisa, Sung, Yun Ju, Noordam, Raymond, Winkler, Thomas, Feitosa, Mary F, Schwander, Karen, Bentley, Amy R, Brown, Michael R, Guo, Xiuqing, Manning, Alisa, Chasman, Daniel I, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Cheng, Ching-Yu, Dorajoo, Rajkumar, Hartwig, Fernando P, Horimoto, ARVR, Li, Changwei, Li-Gao, Ruifang, Liu, Yongmei, Marten, Jonathan, Musani, Solomon K, Ntalla, Ioanna, Rankinen, Tuomo, Richard, Melissa, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Tayo, Bamidele O, Vojinovic, Dina, Warren, Helen R, Xuan, Deng, Alver, Maris, Boissel, Mathilde, Chai, Jin-Fang, Chen, Xu, Christensen, Kaare, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Girotto, Giorgia, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Rueedi, Rico, Shu, Xiao-Ou, Snieder, Harold, Sofer, Tamar, Takeuchi, Fumihiko, Verweij, Niek, Ware, Erin B, Weiss, Stefan, Yanek, Lisa R, Amin, Najaf, Arking, Dan E, Arnett, Donna K, Bergmann, Sven, Boerwinkle, Eric, Brody, Jennifer A, Broeckel, Ulrich, Brumat, Marco, Burke, Gregory, Cabrera, Claudia P, Canouil, Mickaël, Chee, Miao Li, Chen, Yii-Der Ida, Cocca, Massimiliano, Connell, John, de Silva, H Janaka, de Vries, Paul S, Eiriksdottir, Gudny, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Fox, Ervin F, Friedlander, Yechiel, Gao, He, Gigante, Bruna, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven, Ikram, M Arfan, Irvin, Marguerite R, Kähönen, Mika, and Kavousi, Maryam

Subjects
Lifelines Cohort Study, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P

Published
2021

10. Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Author

Sun, Daokun, Richard, Melissa A, Musani, Solomon K, Sung, Yun Ju, Winkler, Thomas W, Schwander, Karen, Chai, Jin Fang, Guo, Xiuqing, Kilpeläinen, Tuomas O, Vojinovic, Dina, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Brown, Michael R, Chitrala, Kumaraswamy, Hartwig, Fernando P, Horimoto, Andrea RVR, Liu, Yongmei, Manning, Alisa K, Noordam, Raymond, Smith, Albert V, Harris, Sarah E, Kühnel, Brigitte, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, van der Most, Peter J, Wang, Rujia, Ware, Erin B, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Arking, Dan E, Arnett, Donna K, Barac, Ana, Boerwinkle, Eric, Broeckel, Ulrich, Chakravarti, Aravinda, Chen, Yii-Der Ida, Cupples, L Adrienne, Davigulus, Martha L, de las Fuentes, Lisa, de Mutsert, Renée, de Vries, Paul S, Delaney, Joseph AC, Roux, Ana V Diez, Dörr, Marcus, Faul, Jessica D, Fretts, Amanda M, Gallo, Linda C, Grabe, Hans Jörgen, Gu, C Charles, Harris, Tamara B, Hartman, Catharina CA, Heikkinen, Sami, Ikram, M Arfan, Isasi, Carmen, Johnson, W Craig, Jonas, Jost Bruno, Kaplan, Robert C, Komulainen, Pirjo, Krieger, Jose E, Levy, Daniel, Study, Lifelines Cohort, Liu, Jianjun, Lohman, Kurt, Luik, Annemarie I, Martin, Lisa W, Meitinger, Thomas, Milaneschi, Yuri, O’Connell, Jeff R, Palmas, Walter R, Peters, Annette, Peyser, Patricia A, Pulkki-Råback, Laura, Raffel, Leslie J, Reiner, Alex P, Rice, Kenneth, Robinson, Jennifer G, Rosendaal, Frits R, Schmidt, Carsten Oliver, Schreiner, Pamela J, Schwettmann, Lars, Shikany, James M, Shu, Xiao-ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A, Sotoodehnia, Nona, Strauch, Konstantin, Tai, E Shyong, Taylor, Kent D, Uitterlinden, André G, van Duijn, Cornelia M, Waldenberger, Melanie, Wee, Hwee-Lin, Wei, Wen-Bin, Wilson, Gregory, Xuan, Deng, and Yao, Jie

Subjects
Hypertension, Mental Health, Genetics, Cardiovascular, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Lifelines Cohort Study
Abstract

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value

Published
2021

11. Early-life stature, preschool cognitive development, schooling attainment, and cognitive functioning in adulthood: a prospective study in four birth cohorts

Author

Kowalski, Alysse, DiGirolamo, Ann, Scerif, Gaia, Mpondo, Feziwe, Belleza, Delia, Nyati, Lukhanyo, Osmond, Clive, Borja, Judith Rafaelita, Carba, Delia, Perez, Tita Lorna, Bechavda, Sonny Agustin, Kroker-Lobos, Maria F, Varghese, Jithin S, Barros, Fernando C, Hartwig, Fernando P, Horta, Bernardo L, Wehrmeister, Fernando C, Stein, Aryeh D, Adair, Linda S, Donati, Georgina, Wray, Charlotte, Richter, Linda M, Norris, Shane A, Stein, Alan, Martorell, Reynaldo, Ramirez-Zea, Manuel, Menezes, Ana M B, Murray, Joseph, Victora, Cesar, Lee, Nanette, and Bas, Isabelita

Published
2023
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12. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author

de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, and Giulianini, Franco

Subjects
Epidemiology, Health Sciences, Substance Misuse, Alcoholism, Alcohol Use and Health, Human Genome, Prevention, Genetics, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Adolescent, Adult, Aged, Alcohol Drinking, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Life Style, Lipids, Male, Middle Aged, Phenotype, Racial Groups, Triglycerides, Vascular Endothelial Growth Factor B, Young Adult, alcohol consumption, cholesterol, gene-environment interactions, gene-lifestyle interactions, genome-wide association studies, lipids, triglycerides, InterAct Consortium, Lifelines Cohort, Groningen, The Netherlands, Mathematical Sciences, Medical and Health Sciences
Abstract

A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

Published
2019

13. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Author

Kilpeläinen, Tuomas O, Bentley, Amy R, Noordam, Raymond, Sung, Yun Ju, Schwander, Karen, Winkler, Thomas W, Jakupović, Hermina, Chasman, Daniel I, Manning, Alisa, Ntalla, Ioanna, Aschard, Hugues, Brown, Michael R, de Las Fuentes, Lisa, Franceschini, Nora, Guo, Xiuqing, Vojinovic, Dina, Aslibekyan, Stella, Feitosa, Mary F, Kho, Minjung, Musani, Solomon K, Richard, Melissa, Wang, Heming, Wang, Zhe, Bartz, Traci M, Bielak, Lawrence F, Campbell, Archie, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Li, Changwei, Lohman, Kurt K, Marten, Jonathan, Sim, Xueling, Smith, Albert V, Tajuddin, Salman M, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Evangelou, Evangelos, Gao, Chuan, Graff, Mariaelisa, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Zhao, Jing Hua, Kraja, Aldi T, Kühnel, Brigitte, Laguzzi, Federica, Lyytikäinen, Leo-Pekka, Nolte, Ilja M, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Rueedi, Rico, Stringham, Heather M, Takeuchi, Fumihiko, van der Most, Peter J, Varga, Tibor V, Verweij, Niek, Ware, Erin B, Wen, Wanqing, Li, Xiaoyin, Yanek, Lisa R, Amin, Najaf, Arnett, Donna K, Boerwinkle, Eric, Brumat, Marco, Cade, Brian, Canouil, Mickaël, Chen, Yii-Der Ida, Concas, Maria Pina, Connell, John, de Mutsert, Renée, de Silva, H Janaka, de Vries, Paul S, Demirkan, Ayşe, Ding, Jingzhong, Eaton, Charles B, Faul, Jessica D, Friedlander, Yechiel, Gabriel, Kelley P, Ghanbari, Mohsen, Giulianini, Franco, Gu, Chi Charles, Gu, Dongfeng, Harris, Tamara B, He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hunt, Steven C, Ikram, M Arfan, Jonas, Jost B, Koh, Woon-Puay, Komulainen, Pirjo, and Krieger, Jose E

Subjects
Lifelines Cohort Study, Humans, Cholesterol, Lipids, Triglycerides, Calcium-Binding Proteins, Muscle Proteins, Microtubule-Associated Proteins, Membrane Proteins, Nerve Tissue Proteins, Transcription Factors, Exercise, Genotype, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, African Continental Ancestry Group, Asian Continental Ancestry Group, European Continental Ancestry Group, Hispanic Americans, Brazil, Female, Male, Lipid Metabolism, Cholesterol, LDL, Cholesterol, HDL, Genome-Wide Association Study, Young Adult, Genetic Loci, LIM-Homeodomain Proteins, and over, HDL, LDL
Abstract

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

Published
2019

14. Mendelian randomization evaluation of causal effects of fibrinogen on incident coronary heart disease

Author

Ward-Caviness, Cavin K, de Vries, Paul S, Wiggins, Kerri L, Huffman, Jennifer E, Yanek, Lisa R, Bielak, Lawrence F, Giulianini, Franco, Guo, Xiuqing, Kleber, Marcus E, Kacprowski, Tim, Groß, Stefan, Petersman, Astrid, Smith, George Davey, Hartwig, Fernando P, Bowden, Jack, Hemani, Gibran, Müller-Nuraysid, Martina, Strauch, Konstantin, Koenig, Wolfgang, Waldenberger, Melanie, Meitinger, Thomas, Pankratz, Nathan, Boerwinkle, Eric, Tang, Weihong, Fu, Yi-Ping, Johnson, Andrew D, Song, Ci, de Maat, Moniek PM, Uitterlinden, André G, Franco, Oscar H, Brody, Jennifer A, McKnight, Barbara, Chen, Yii-Der Ida, Psaty, Bruce M, Mathias, Rasika A, Becker, Diane M, Peyser, Patricia A, Smith, Jennifer A, Bielinski, Suzette J, Ridker, Paul M, Taylor, Kent D, Yao, Jie, Tracy, Russell, Delgado, Graciela, Trompet, Stella, Sattar, Naveed, Jukema, J Wouter, Becker, Lewis C, Kardia, Sharon LR, Rotter, Jerome I, März, Winfried, Dörr, Marcus, Chasman, Daniel I, Dehghan, Abbas, O’Donnell, Christopher J, Smith, Nicholas L, Peters, Annette, and Morrison, Alanna C

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Heart Disease, Cardiovascular, Prevention, Human Genome, Heart Disease - Coronary Heart Disease, Alleles, Coronary Disease, Fibrinogen, Genetic Pleiotropy, Genetic Variation, Genome-Wide Association Study, Humans, Incidence, Mendelian Randomization Analysis, Models, Genetic, Multivariate Analysis, Myocardial Infarction, Odds Ratio, General Science & Technology
Abstract

BackgroundFibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies.Methods and findingsWe evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI). In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models.ConclusionsA small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies.

Published
2019

16. Health and development from preconception to 20 years of age and human capital

Author

Black, Robert E, Liu, Li, Hartwig, Fernando P, Villavicencio, Francisco, Rodriguez-Martinez, Andrea, Vidaletti, Luis P, Perin, Jamie, Black, Maureen M, Blencowe, Hannah, You, Danzhen, Hug, Lucia, Masquelier, Bruno, Cousens, Simon, Gove, Amber, Vaivada, Tyler, Yeung, Diana, Behrman, Jere, Martorell, Reynaldo, Osmond, Clive, Stein, Aryeh D, Adair, Linda S, Fall, Caroline H D, Horta, Bernardo, Menezes, Ana M B, Ramirez-Zea, Manuel, Richter, Linda M, Patton, George C, Bendavid, Eran, Ezzati, Majid, Bhutta, Zulfiqar A, Lawn, Joy E, and Victora, Cesar G

Published
2022
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17. Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs

Author

Victora, Cesar G, Hartwig, Fernando P, Vidaletti, Luis P, Martorell, Reynaldo, Osmond, Clive, Richter, Linda M, Stein, Aryeh D, Barros, Aluisio J D, Adair, Linda S, Barros, Fernando C, Bhargava, Santosh K, Horta, Bernardo L, Kroker-Lobos, Maria F, Lee, Nanette R, Menezes, Ana Maria B, Murray, Joseph, Norris, Shane A, Sachdev, Harshpal S, Stein, Alan, Varghese, Jithin S, Bhutta, Zulfiqar A, and Black, Robert E

Published
2022
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18. The Median and the Mode as Robust Meta-Analysis Estimators in the Presence of Small-Study Effects and Outliers

Author

Hartwig, Fernando P., Davey Smith, George, Schmidt, Amand F., Sterne, Jonathan A. C., Higgins, Julian P. T., and Bowden, Jack

Abstract

Meta-analyses based on systematic literature reviews are commonly used to obtain a quantitative summary of the available evidence on a given topic. However, the reliability of any meta-analysis is constrained by that of its constituent studies. One major limitation is the possibility of small-study effects, when estimates from smaller and larger studies differ systematically. Small-study effects may result from reporting biases (ie, publication bias), from inadequacies of the included studies that are related to study size, or from reasons unrelated to bias. We propose two estimators based on the median and mode to increase the reliability of findings in a meta-analysis by mitigating the influence of small-study effects. By re-examining data from published meta-analyses and by conducting a simulation study, we show that these estimators offer robustness to a range of plausible bias mechanisms, without making explicit modelling assumptions. They are also robust to outlying studies without explicitly removing such studies from the analysis. When meta-analyses are suspected to be at risk of bias because of small-study effects, we recommend reporting the mean, median and modal pooled estimates.

Published
2020
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19. Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function.

Author

Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, and Gharib, Sina A

Subjects
Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive
Abstract

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

Published
2018

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

Author

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

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

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

Published
2018

21. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries.

Author

Feitosa, Mary F, Kraja, Aldi T, Chasman, Daniel I, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K, Li, Changwei, Bentley, Amy R, Brown, Michael R, Schwander, Karen, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Dorajoo, Rajkumar, Fisher, Virginia, Hartwig, Fernando P, Horimoto, Andrea RVR, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Wojczynski, Mary K, Alver, Maris, Boissel, Mathilde, Cai, Qiuyin, Campbell, Archie, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, He, Meian, Hsu, Fang-Chi, Jackson, Anne U, Kähönen, Mika, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Luan, Jian'an, Matoba, Nana, Nolte, Ilja M, Padmanabhan, Sandosh, Riaz, Muhammad, Rueedi, Rico, Robino, Antonietta, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Vitart, Veronique, Wang, Yajuan, Ware, Erin B, Warren, Helen R, Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Boerwinkle, Eric, Borecki, Ingrid, Broeckel, Ulrich, Brown, Morris, Brumat, Marco, Burke, Gregory L, Canouil, Mickaël, Chakravarti, Aravinda, Charumathi, Sabanayagam, Ida Chen, Yii-Der, Connell, John M, Correa, Adolfo, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Deng, Xuan, Ding, Jingzhong, Duan, Qing, Eaton, Charles B, and Ehret, Georg

Subjects
InterAct Consortium, Humans, Hypertension, Genetic Predisposition to Disease, Cohort Studies, Pedigree, Alcohol Drinking, Blood Pressure, Polymorphism, Single Nucleotide, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Continental Population Groups, Female, Male, Genome-Wide Association Study, Young Adult, Gene-Environment Interaction, General Science & Technology
Abstract

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Published
2018

22. Time-dependent decay of detectable antibodies against SARS-CoV-2: A comparison of ELISA with two batches of a lateral-flow test

Author

Silveira, Mariangela F, Mesenburg, Marilia A, Dellagostin, Odir A, de Oliveira, Natasha R, Maia, Mara AC, Santos, Francisco D, Vale, André, Menezes, Ana M B, Victora, Gabriel D, Victora, Cesar G, Barros, Aluisio JD, Vidaletti, Luis Paulo, Hartwig, Fernando P, Barros, Fernando C, Hallal, Pedro C, and Horta, Bernardo L

Published
2021
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26. Population-based surveys of antibodies against SARS-CoV-2 in Southern Brazil

Author

Silveira, Mariângela F., Barros, Aluísio J. D., Horta, Bernardo L., Pellanda, Lúcia C., Victora, Gabriel D., Dellagostin, Odir A., Struchiner, Claudio J., Burattini, Marcelo N., Valim, Andréia R. M., Berlezi, Evelise M., Mesa, Jeovany M., Ikeda, Maria Letícia R., Mesenburg, Marilia A., Mantesso, Marina, Dall’Agnol, Marinel M., Bittencourt, Raqueli A., Hartwig, Fernando P., Menezes, Ana M. B., Barros, Fernando C., Hallal, Pedro C., and Victora, Cesar G.

Published
2020
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28. SMIM1 absence is associated with reduced energy expenditure and excess weight

Author

Banasik, Karina, Bay, Jakob, Boldsen, Jens Kjærgaard, Brodersen, Thorsten, Brunak, Søren, Burgdorf, Kristoffer, Chalmer, Mona Ameri, Didriksen, Maria, Dinh, Khoa Manh, Dowsett, Joseph, Erikstrup, Christian, Feenstra, Bjarke, Geller, Frank, Gudbjartsson, Daniel, Hansen, Thomas Folkmann, Hindhede, Lotte, Hjalgrim, Henrik, Jacobsen, Rikke Louise, Jemec, Gregor, Jensen, Bitten Aagaard, Kaspersen, Katrine, Kjerulff, Bertram Dalskov, Kogelman, Lisette, Hørup Larsen, Margit Anita, Louloudis, Ioannis, Lundgaard, Agnete, Susan, Mikkelsen, Christina, Nissen, Ioanna, Nyegaard, Mette, Ostrowski, Sisse Rye, Pedersen, Ole Birger, Henriksen, Alexander Pil, Rohde, Palle Duun, Rostgaard, Klaus, Schwinn, Michael, Stefansson, Kari, Stefánsson, Hreinn, Sørensen, Erik, þorsteinsdóttir, Unnur, Thørner, Lise Wegner, Bruun, Mie Topholm, Ullum, Henrik, Werge, Thomas, Westergaard, David, Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J., Luan, Jian’an, Willems, Sara M., Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S., Mägi, Reedik, Waage, Johannes, Li-Gao, Ruifang, Katie Chan, Kei Hang, Yao, Jie, Anasanti, Mila D., Chu, Audrey Y., Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E., Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D., Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil V.R., Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P., Cabrera, Claudia P., Cade, Brian E., Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H., Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E., Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A., Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P., He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A., Kim, Young Jin, Kleber, Marcus E., Kooner, Ishminder K., Lai, Shuiqing, Lange, Leslie A., Langefeld, Carl D., Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E., Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S., Robertson, Neil R., Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E., Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V., Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J., Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J., Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R., Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R., Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan J.L., Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N., Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R., Bowden, Donald W., Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P., Goel, Anuj, Han, Sohee, Hartman, Catharina A., Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E., Joshi, Peter K., Kalyani, Rita R., Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A., Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J., Norris, Jill M., Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F., Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M., Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul R.H.J., Tremoli, Elena, Tsai, Michael Y., Uitterlinden, Andre, van Dam, Rob M., van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V., Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, Willems van Dijk, Ko, Zemunik, Tatijana, Abecasis, Goncalo R., Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E., An, Ping, Aviles-Santa, Larissa, Becker, Diane M., Beilin, Lawrence J., Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O., Bønnelykke, Klaus, Boomsma, D.I., Bottinger, Erwin P., Buchanan, Thomas A., Canouil, Mickaël, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Ida Chen, Yii-Der, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, Janaka de Silva, H., Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C., Franks, Paul W., Frayling, Timothy M., Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L., Huang, Wei, Ingelsson, Erik, James, Pankow S., Jarvelin, Marjo-Ritta, Jonas, Jost B., Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J., Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik K.E., Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O., Mori, Trevor A., Munroe, Patricia B., Njølstad, Inger, O'Connell, Jeffrey R., Oldehinkel, Albertine J., Ong, Ken K., Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D., Pedersen, Oluf, Pennell, Craig E., Porteous, David J., Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M., Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-Ou, Slagboom, P. Eline, Small, Kerrin S., Smith, Blair H., Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D., Stanton, Alice, Steves, Claire J., Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E. Shyong, Timpson, Nicholas J., Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja G.M., Wagenknecht, Lynne E., Walker, Mark, Wang, Ya X., Wareham, Nick J., Watanabe, Richard M., Watkins, Hugh, Wei, Wen B., Wickremasinghe, Ananda R., Willemsen, Gonneke, Wilson, James F., Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H., Yanek, Lisa R., Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B., Rotter, Jerome I., Gloyn, Anna L., McCarthy, Mark I., Dupuis, Josée, Meigs, James B., Scott, Robert A., Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen C.J., Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês, Stefanucci, Luca, Moslemi, Camous, Tomé, Ana R., Virtue, Samuel, Bidault, Guillaume, Gleadall, Nicholas S., Watson, Laura P.E., Kwa, Jing E., Burden, Frances, Farrow, Samantha, Võsa, Urmo, Burling, Keith, Walker, Lindsay, Ord, John, Barker, Peter, Warner, James, Frary, Amy, Renhstrom, Karola, Ashford, Sofie E., Piper, Jo, Biggs, Gail, Erber, Wendy N., Hoffman, Gary J., Schoenmakers, Nadia, Rieneck, Klaus, Dziegiel, Morten H., Azzu, Vian, Vacca, Michele, Aparicio, Hugo Javier, Hui, Qin, Cho, Kelly, Sun, Yan V., Wilson, Peter W., Bayraktar, Omer A., Vidal-Puig, Antonio, Ostrowski, Sisse R., Astle, William J., Olsson, Martin L., Storry, Jill R., Pedersen, Ole B., Ouwehand, Willem H., Chatterjee, Krishna, Vuckovic, Dragana, and Frontini, Mattia

Published
2024
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29. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, primary, Schwander, Karen L., additional, Brown, Michael R., additional, Bentley, Amy R., additional, Winkler, Thomas W., additional, Sung, Yun Ju, additional, Munroe, Patricia B., additional, Miller, Clint L., additional, Aschard, Hugo, additional, Aslibekyan, Stella, additional, Bartz, Traci M., additional, Bielak, Lawrence F., additional, Chai, Jin Fang, additional, Cheng, Ching-Yu, additional, Dorajoo, Rajkumar, additional, Feitosa, Mary F., additional, Guo, Xiuqing, additional, Hartwig, Fernando P., additional, Horimoto, Andrea, additional, Kolčić, Ivana, additional, Lim, Elise, additional, Liu, Yongmei, additional, Manning, Alisa K., additional, Marten, Jonathan, additional, Musani, Solomon K., additional, Noordam, Raymond, additional, Padmanabhan, Sandosh, additional, Rankinen, Tuomo, additional, Richard, Melissa A., additional, Ridker, Paul M., additional, Smith, Albert V., additional, Vojinovic, Dina, additional, Zonderman, Alan B., additional, Alver, Maris, additional, Boissel, Mathilde, additional, Christensen, Kaare, additional, Freedman, Barry I., additional, Gao, Chuan, additional, Giulianini, Franco, additional, Harris, Sarah E., additional, He, Meian, additional, Hsu, Fang-Chi, additional, Kühnel, Brigitte, additional, Laguzzi, Federica, additional, Li, Xiaoyin, additional, Lyytikäinen, Leo-Pekka, additional, Nolte, Ilja M., additional, Poveda, Alaitz, additional, Rauramaa, Rainer, additional, Riaz, Muhammad, additional, Robino, Antonietta, additional, Sofer, Tamar, additional, Takeuchi, Fumihiko, additional, Tayo, Bamidele O., additional, van der Most, Peter J., additional, Verweij, Niek, additional, Ware, Erin B., additional, Weiss, Stefan, additional, Wen, Wanqing, additional, Yanek, Lisa R., additional, Zhan, Yiqiang, additional, Amin, Najaf, additional, Arking, Dan E., additional, Ballantyne, Christie, additional, Boerwinkle, Eric, additional, Brody, Jennifer A., additional, Broeckel, Ulrich, additional, Campbell, Archie, additional, Canouil, Mickaël, additional, Chai, Xiaoran, additional, Chen, Yii-Der Ida, additional, Chen, Xu, additional, Chitrala, Kumaraswamy Naidu, additional, Concas, Maria Pina, additional, de Faire, Ulf, additional, de Mutsert, Renée, additional, de Silva, H. Janaka, additional, de Vries, Paul S., additional, Do, Ahn, additional, Faul, Jessica D., additional, Fisher, Virginia, additional, Floyd, James S., additional, Forrester, Terrence, additional, Friedlander, Yechiel, additional, Girotto, Giorgia, additional, Gu, C. Charles, additional, Hallmans, Göran, additional, Heikkinen, Sami, additional, Heng, Chew-Kiat, additional, Homuth, Georg, additional, Hunt, Steven, additional, Ikram, M. Arfan, additional, Jacobs, David R., additional, Kavousi, Maryam, additional, Khor, Chiea Chuen, additional, Kilpeläinen, Tuomas O., additional, Koh, Woon-Puay, additional, Komulainen, Pirjo, additional, Langefeld, Carl D., additional, Liang, Jingjing, additional, Liu, Kiang, additional, Liu, Jianjun, additional, Lohman, Kurt, additional, Mägi, Reedik, additional, Manichaikul, Ani W., additional, McKenzie, Colin A., additional, Meitinger, Thomas, additional, Milaneschi, Yuri, additional, Nauck, Matthias, additional, Nelson, Christopher P., additional, O’Connell, Jeffrey R., additional, Palmer, Nicholette D., additional, Pereira, Alexandre C., additional, Perls, Thomas, additional, Peters, Annette, additional, Polašek, Ozren, additional, Raitakari, Olli T., additional, Rice, Kenneth, additional, Rice, Treva K., additional, Rich, Stephen S., additional, Sabanayagam, Charumathi, additional, Schreiner, Pamela J., additional, Shu, Xiao-Ou, additional, Sidney, Stephen, additional, Sims, Mario, additional, Smith, Jennifer A., additional, Starr, John M., additional, Strauch, Konstantin, additional, Tai, E. Shyong, additional, Taylor, Kent D., additional, Tsai, Michael Y., additional, Uitterlinden, André G., additional, van Heemst, Diana, additional, Waldenberger, Melanie, additional, Wang, Ya-Xing, additional, Wei, Wen-Bin, additional, Wilson, Gregory, additional, Xuan, Deng, additional, Yao, Jie, additional, Yu, Caizheng, additional, Yuan, Jian-Min, additional, Zhao, Wei, additional, Becker, Diane M., additional, Bonnefond, Amélie, additional, Bowden, Donald W., additional, Cooper, Richard S., additional, Deary, Ian J., additional, Divers, Jasmin, additional, Esko, Tõnu, additional, Franks, Paul W., additional, Froguel, Philippe, additional, Gieger, Christian, additional, Jonas, Jost B., additional, Kato, Norihiro, additional, Lakka, Timo A., additional, Leander, Karin, additional, Lehtimäki, Terho, additional, Magnusson, Patrik K. E., additional, North, Kari E., additional, Ntalla, Ioanna, additional, Penninx, Brenda, additional, Samani, Nilesh J., additional, Snieder, Harold, additional, Spedicati, Beatrice, additional, van der Harst, Pim, additional, Völzke, Henry, additional, Wagenknecht, Lynne E., additional, Weir, David R., additional, Wojczynski, Mary K., additional, Wu, Tangchun, additional, Zheng, Wei, additional, Zhu, Xiaofeng, additional, Bouchard, Claude, additional, Chasman, Daniel I., additional, Evans, Michele K., additional, Fox, Ervin R., additional, Gudnason, Vilmundur, additional, Hayward, Caroline, additional, Horta, Bernardo L., additional, Kardia, Sharon L. R., additional, Krieger, Jose Eduardo, additional, Mook-Kanamori, Dennis O., additional, Peyser, Patricia A., additional, Province, Michael M., additional, Psaty, Bruce M., additional, Rudan, Igor, additional, Sim, Xueling, additional, Smith, Blair H., additional, van Dam, Rob M., additional, van Duijn, Cornelia M., additional, Wong, Tien Yin, additional, Arnett, Donna K., additional, Rao, Dabeeru C., additional, Gauderman, James, additional, Liu, Ching-Ti, additional, Morrison, Alanna C., additional, Rotter, Jerome I., additional, and Fornage, Myriam, additional

Published
2023
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30. Guidelines for performing Mendelian randomization investigations: update for summer 2023

Author

Burgess, Stephen, primary, Davey Smith, George, additional, Davies, Neil M., additional, Dudbridge, Frank, additional, Gill, Dipender, additional, Glymour, M. Maria, additional, Hartwig, Fernando P., additional, Kutalik, Zoltán, additional, Holmes, Michael V., additional, Minelli, Cosetta, additional, Morrison, Jean V., additional, Pan, Wei, additional, Relton, Caroline L., additional, and Theodoratou, Evropi, additional

Published
2023
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32. Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis

Author

Zengini, Eleni, Hatzikotoulas, Konstantinos, Tachmazidou, Ioanna, Steinberg, Julia, Hartwig, Fernando P., Southam, Lorraine, Hackinger, Sophie, Boer, Cindy G., Styrkarsdottir, Unnur, Gilly, Arthur, Suveges, Daniel, Killian, Britt, Ingvarsson, Thorvaldur, Jonsson, Helgi, Babis, George C., McCaskie, Andrew, Uitterlinden, Andre G., van Meurs, Joyce B. J., Thorsteinsdottir, Unnur, Stefansson, Kari, Davey Smith, George, Wilkinson, Jeremy M., and Zeggini, Eleftheria

Published
2018
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33. Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Author

de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., Fornage, Myriam, de las Fuentes, Lisa, Schwander, Karen L., Brown, Michael R., Bentley, Amy R., Winkler, Thomas W., Sung, Yun Ju, Munroe, Patricia B., Miller, Clint L., Aschard, Hugo, Aslibekyan, Stella, Bartz, Traci M., Bielak, Lawrence F., Chai, Jin Fang, Cheng, Ching Yu, Dorajoo, Rajkumar, Feitosa, Mary F., Guo, Xiuqing, Hartwig, Fernando P., Horimoto, Andrea, Kolčić, Ivana, Lim, Elise, Liu, Yongmei, Manning, Alisa K., Marten, Jonathan, Musani, Solomon K., Noordam, Raymond, Padmanabhan, Sandosh, Rankinen, Tuomo, Richard, Melissa A., Ridker, Paul M., Smith, Albert V., Vojinovic, Dina, Zonderman, Alan B., Alver, Maris, Boissel, Mathilde, Christensen, Kaare, Freedman, Barry I., Gao, Chuan, Giulianini, Franco, Harris, Sarah E., He, Meian, Hsu, Fang Chi, Kühnel, Brigitte, Laguzzi, Federica, Li, Xiaoyin, Lyytikäinen, Leo Pekka, Nolte, Ilja M., Poveda, Alaitz, Rauramaa, Rainer, Riaz, Muhammad, Robino, Antonietta, Sofer, Tamar, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Verweij, Niek, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhan, Yiqiang, Amin, Najaf, Arking, Dan E., Ballantyne, Christie, Boerwinkle, Eric, Brody, Jennifer A., Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Chai, Xiaoran, Chen, Yii Der Ida, Chen, Xu, Chitrala, Kumaraswamy Naidu, Concas, Maria Pina, de Faire, Ulf, de Mutsert, Renée, de Silva, H. Janaka, de Vries, Paul S., Do, Ahn, Faul, Jessica D., Fisher, Virginia, Floyd, James S., Forrester, Terrence, Friedlander, Yechiel, Girotto, Giorgia, Gu, C. Charles, Hallmans, Göran, Heikkinen, Sami, Heng, Chew Kiat, Homuth, Georg, Hunt, Steven, Ikram, M. Arfan, Jacobs, David R., Kavousi, Maryam, Khor, Chiea Chuen, Kilpeläinen, Tuomas O., Koh, Woon Puay, Komulainen, Pirjo, Langefeld, Carl D., Liang, Jingjing, Liu, Kiang, Liu, Jianjun, Lohman, Kurt, Mägi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Milaneschi, Yuri, Nauck, Matthias, Nelson, Christopher P., O’Connell, Jeffrey R., Palmer, Nicholette D., Pereira, Alexandre C., Perls, Thomas, Peters, Annette, Polašek, Ozren, Raitakari, Olli T., Rice, Kenneth, Rice, Treva K., Rich, Stephen S., Sabanayagam, Charumathi, Schreiner, Pamela J., Shu, Xiao Ou, Sidney, Stephen, Sims, Mario, Smith, Jennifer A., Starr, John M., Strauch, Konstantin, Tai, E. Shyong, Taylor, Kent D., Tsai, Michael Y., Uitterlinden, André G., van Heemst, Diana, Waldenberger, Melanie, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Xuan, Deng, Yao, Jie, Yu, Caizheng, Yuan, Jian Min, Zhao, Wei, Becker, Diane M., Bonnefond, Amélie, Bowden, Donald W., Cooper, Richard S., Deary, Ian J., Divers, Jasmin, Esko, Tõnu, Franks, Paul W., Froguel, Philippe, Gieger, Christian, Jonas, Jost B., Kato, Norihiro, Lakka, Timo A., Leander, Karin, Lehtimäki, Terho, Magnusson, Patrik K.E., North, Kari E., Ntalla, Ioanna, Penninx, Brenda, Samani, Nilesh J., Snieder, Harold, Spedicati, Beatrice, van der Harst, Pim, Völzke, Henry, Wagenknecht, Lynne E., Weir, David R., Wojczynski, Mary K., Wu, Tangchun, Zheng, Wei, Zhu, Xiaofeng, Bouchard, Claude, Chasman, Daniel I., Evans, Michele K., Fox, Ervin R., Gudnason, Vilmundur, Hayward, Caroline, Horta, Bernardo L., Kardia, Sharon L.R., Krieger, Jose Eduardo, Mook-Kanamori, Dennis O., Peyser, Patricia A., Province, Michael M., Psaty, Bruce M., Rudan, Igor, Sim, Xueling, Smith, Blair H., van Dam, Rob M., van Duijn, Cornelia M., Wong, Tien Yin, Arnett, Donna K., Rao, Dabeeru C., Gauderman, James, Liu, Ching Ti, Morrison, Alanna C., Rotter, Jerome I., and Fornage, Myriam

Abstract

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods:A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational a

Published
2023

35. Early-life stature, preschool cognitive development, schooling attainment, and cognitive functioning in adulthood: a prospective study in four birth cohorts

Author

Stein, Aryeh D, primary, Adair, Linda S, additional, Donati, Georgina, additional, Wray, Charlotte, additional, Richter, Linda M, additional, Norris, Shane A, additional, Stein, Alan, additional, Martorell, Reynaldo, additional, Ramirez-Zea, Manuel, additional, Menezes, Ana M B, additional, Murray, Joseph, additional, Victora, Cesar, additional, Lee, Nanette, additional, Bas, Isabelita, additional, Kowalski, Alysse, additional, DiGirolamo, Ann, additional, Scerif, Gaia, additional, Mpondo, Feziwe, additional, Belleza, Delia, additional, Nyati, Lukhanyo, additional, Osmond, Clive, additional, Borja, Judith Rafaelita, additional, Carba, Delia, additional, Perez, Tita Lorna, additional, Bechavda, Sonny Agustin, additional, Kroker-Lobos, Maria F, additional, Varghese, Jithin S, additional, Barros, Fernando C, additional, Hartwig, Fernando P, additional, Horta, Bernardo L, additional, and Wehrmeister, Fernando C, additional

Published
2023
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36. Genome-wide burden and association analyses implicate copy number variations in asthma risk among children and young adults from Latin America

Author

Oliveira, Pablo, Costa, Gustavo N. O., Damasceno, Andresa K. A., Hartwig, Fernando P., Barbosa, George C. G., Figueiredo, Camila A., Ribeiro-Silva, Rita de C., Pereira, Alexandre, Lima-Costa, M. Fernanda, Kehdy, Fernanda S., Tarazona-Santos, Eduardo, Horta, Bernardo L., Rodrigues, Laura C., Fiaccone, Rosemeire L., and Barreto, Maurício L.

Published
2018
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37. Uso de mascarillas durante la pandemia de COVID-19 en Brasil: resultados del estudio EPICOVID19-BR

Author

Jacques, Nadège, Silveira, Mariângela Freitas da, Hallal, Pedro C., Menezes, Ana M. B., Horta, Bernardo Lessa, Mesenburg, Marilia Arndt, Hartwig, Fernando P., and Barros, Aluísio J. D.

Subjects
Encuesta, Inquérito, N95 Respirators, Epidemiology, COVID-19, Epidemiología, Epidemiologia, Disease Prevention, Survey, Prevención de Enfermedades, Respiradores N95, Prevenção de Doenças
Abstract

A pandemia de COVID-19 já causou mais de 399 milhões de infecções e custou a vida de mais de cinco milhões de pessoas no mundo, até 3 de março de 2022. Para reduzir a taxa de infecção, uma série de medidas de prevenção indicadas pela Organização Mundial da Saúde (OMS) foram adotadas pelos países, entre elas, o uso de máscara. O objetivo deste estudo é descrever a utilização de máscara na população brasileira, através da análise de dados do EPICOVID19-BR, um estudo de base populacional realizado em 133 cidades do país, em quatro fases entre março e agosto de 2020. A proporção de indivíduos que preferiram usar máscara quando saíam de casa foi de 97,9% (IC95%: 97,8-98,0). O entrevistador não visualizou a máscara do entrevistado em 50% (IC95%: 49,9-51,1) dos casos no momento da entrevista, no entanto, entre a fase uma e quatro da pesquisa, observou-se uma diminuição de 4,4 pontos percentuais na proporção de entrevistados que não usaram máscara no momento da entrevista. A não visualização da máscara foi mais observada em mulheres, participantes com idade entre 10-19 e 20-29 anos, de cor de pele indígena, preta, e parda, entre as pessoas com Ensinos Fundamental e Médio e na Região Centro-oeste. O uso de máscara de tecido foi predominante 91,4% (IC95%: 91,2-91,5) com um aumento de 4,9 pontos percentuais entre as fases 1 e 4. Os resultados do estudo trazem informações importantes para reforçar as políticas de controle de COVID-19 no Brasil. O alto percentual de pessoas sem máscara na hora da entrevista sugere que ainda é importante reforçar o aspecto preventivo e de autocuidado, não fazendo do uso da máscara algo apenas ligado à obrigatoriedade. By March 3, 2022, the COVID-19 pandemic has caused more than 399 million infections and claimed the lives of more than five million people worldwide. To reduce infection rates, a series of prevention measures indicated by the World Health Organization (WHO) were adopted by countries, including the use of masks. This study aims to describe mask use in Brazil via data analysis from the EPICOVID19-BR, a population-based study conducted in 133 cities in the country in four phases between March and August 2020. The proportion of individuals who reported wearing a mask when they left their homes was 97.9% (95%CI: 97.8-98.0). The interviewer did not see interviewees’ mask in 50% (95%CI: 49.9-51.1) of the cases at the time of the interview. However, between phase one and four of the survey, we observed a 4.4% decrease in the proportion of interviewees who failed to wear masks at the time of the interview. Mask non-visualization was more prominent in women, participants aged 10-19 and 20-29 years of indigenous, black, and brown skin color, and those with elementary and high school education and in the Central-West Region. The use of cloth masks showed a 91.4% predominance (95%CI: 91.2-1.5) with a 4.9% increase between phases 1 and 4. The results of the study bring important information to reinforce COVID-19 control policies in Brazil. The high percentage of people who failed to wear masks at the time of the interview suggests that it is still important to reinforce prevention and self-care, rather than relating mask wear to a mandatory measure. La pandemia del COVID-19 ha provocado más de 399 millones de infecciones y se ha cobrado la vida de más de cinco millones de personas en todo el mundo hasta el 3 de Marzo de 2022. Para reducir la tasa de contagios, los países adoptaron una serie de medidas de prevención indicadas por la Organización Mundial de la Salud (OMS), entre ellas el uso de mascarillas. El objetivo de este estudio es describir el uso de mascarillas en la población brasileña, utilizando el análisis de datos de EPICOVID19-BR, un estudio de base poblacional realizado en 133 ciudades del país, en cuatro fases entre marzo y agosto de 2020. La proporción de personas que informaron usar mascarillas al salir de casa fue del 97,9% (IC95%: 97,8-98,0). El entrevistador no vio la mascarilla del entrevistado en el 50% (IC95%: 49,9-51,1) de los casos al momento de la entrevista, sin embargo entre las fases uno y cuatro de la investigación se observó una disminución de 4,4 puntos porcentuales en la proporción de los encuestados que no llevaban mascarilla durante la entrevista. Se observó una mayor visualización de falta de uso de mascarillas en las mujeres, en participantes con edades entre 10-19 y 20-29 años, de color de piel indígena, negra y parda, entre personas con educación primaria y secundaria y en la Región Centro-oeste. Hubo un mayor predominio de uso de mascarillas de tela en el 91,4% (IC95%: 91,2-91,5) con un aumento de 4,9 puntos porcentuales entre las fases 1 y 4. Los resultados muestran la importancia de fortalecer las políticas de prevención del COVID-19 en Brasil. El alto porcentaje de personas sin mascarilla al momento de la entrevista sugiere que es importante reforzar la prevención y el autocuidado en general no solo relacionado a la obligatoriedad en el uso de mascarillas.

Published
2022

38. COVID-19 y atención ambulatoria: una encuesta domiciliaria a escala nacional

Author

Horta, Bernardo L., Silveira, Mariângela F., Barros, Aluísio J. D., Hartwig, Fernando P., Dias, Mariane S., Menezes, Ana M. B., and Hallal, Pedro C.

Subjects
Encuesta, Inquérito, Assistência Ambulatorial, Atención Ambulatoria, Epidemiology, Outpatient Care, Iniquidade Social, Social Inequity, COVID-19, Epidemiología, Iniquidad Social, Survey, Epidemiologia
Abstract

We aimed to assess the proportion of the population in 133 Brazilian municipalities who - from March to August 2020 - had a health problem but failed to seek care or failed to attend to a health service for routine appointment or examination. We conducted a household survey from August 24-27 in 133 Brazilian cities by asking the subjects if, since the beginning of the COVID-19 pandemic in March 2020, they had suffered from a health problem but did not seek care or failed to attend to a routine or screening examination. Poisson regression was used for the analyses. We interviewed 33,250 subjects and 11.8% (95%CI: 11.4-12.1) reported that, since March 2020, they failed to seek care despite being ill, 17.3% (95%CI: 16.9-17.7) failed to attend to a routine or screening examination and 23.9% (95%CI: 23.4-24.4) reported one or both outcomes. Health service closure and fear of the COVID-19 infection were the main reasons for not seeking care. Women and the poorest were more likely to not look for a health service, despite having a health problem or a scheduled routine appointment. On the other hand, those subjects who self-identified as white were less likely to not look for a health service. The COVID-19 pandemic is more critical for the indigenous people and the poorest, and these people are also more likely to not seek care for other health conditions during the pandemic. O estudo teve como objetivo avaliar a proporção da população de 133 cidades brasileiras que apresentou algum problema de saúde entre março e agosto de 2020, mas que deixou de procurar atendimento, ou que deixou de buscar um serviço de saúde para consultas ou exames de rotina. Foram realizadas entrevistas domiciliares entre 24 e 27 de agosto de 2020 em 133 áreas urbanas brasileiras. Perguntava-se aos indivíduos se, desde o início da pandemia de COVID-19 em março de 2020, haviam sofrido algum problema de saúde mais não haviam procurado atendimento, ou se haviam deixado de realizar consultas ou exames de rotina. A regressão de Poisson foi utilizada para as análises. Foram entrevistados 33.250 indivíduos, entre os quais 11,8% (IC95%: 11,4-12,1) relataram que desde março de 2020 haviam deixado de procurar atendimento apesar de estarem doentes, 17,3% (IC95%: 16,9-17,7) haviam deixado de comparecer a consultas de rotina ou triagem e 23,9% (IC95%: 23,4-24,4) relataram um ou ambos os desfechos. O fechamento dos serviços de saúde e o medo da infecção pelo SARS-CoV-2 foram os principais motivos para não buscar atendimento. As mulheres e os indivíduos com menor nível socioeconômico mostraram maior probabilidade de não procurarem serviços de saúde em caso de doença, ou de faltar a consultas de rotina previamente agendadas. Por outro lado, indivíduos que se identificavam como brancos eram menos propensos a deixar de procurar os serviços de saúde. A pandemia da COVID-19 está afetando mais duramente os indígenas e as pessoas com menor nível socioeconômico, que também são mais propensos a deixar de procurar atendimento para outras condições de saúde durante a pandemia. Se realizó un estudio con el fin de evaluar la proporción de población en 133 ciudades brasileñas que -de marzo a agosto 2020- tuvieron un problema de salud, pero no consiguieron buscar cuidados, o presentarse en un servicio de salud para consultas de rutina o exámenes. Se llevó a cabo una encuesta domiciliaria entre el 24 y 27 de agosto en 133 áreas urbanas brasileñas. A los encuestados se les preguntó si, desde el principio de la pandemia de COVID-19 en marzo de 2020, habían sufrido algún problema de salud, pero no habían buscado asistencia, o no consiguieron presentarse a exámenes de rutina o de exploración. Se utilizó una regresión de Poisson para los análisis. Se entrevistó a 33.250 individuos, y un 11,8% (IC95%: 11,4-12,1) informaron que desde marzo de 2020 no consiguieron buscar asistencia, a pesar de estar enfermos, un 17,3% (IC95%: 16,9-17,7) no consiguieron presentarse a exámenes de rutina o visitas de exploración, y un 23,9% (IC95%: 23,4-24,4) informaron de uno o ambos resultados. El cierre de los servicios de salud y el miedo a contraer COVID-19 fueron las razones principales para no buscar cuidados. Las mujeres y aquellos que tenían un estatus socioeconómico bajo eran más propensos a no buscar asistencia sanitaria, tanto si tenían un problema médico, como para un chequeo rutinario o se saltaban una cita médica programada. Por otro lado, estas personas que se autoidentificaron como blancas eran menos propensas a no buscar asistencia sanitaria. La pandemia de COVID-19 está golpeando duramente a los indígenas y a quienes tienen un estatus socioeconómico bajo, y estas personas también son más propensas a no conseguir buscar asistencia sanitaria relacionada con otros problemas de salud durante la pandemia.

Published
2022

39. Health and development from preconception to 20 years of age and human capital

Author

Black, Robert E., Liu, Li, Hartwig, Fernando P., Villavicencio, Francisco, Rodriguez-Martin, Andrea, Vidaletti, Luis P, Perin, Jamie, Black, Maureen M., Blencowe, Hannah, You, Danzhen, Hug, Lucia, Masquelier, Bruno, and Osmond, Clive

Abstract

Optimal health and development from preconception to adulthood are critical for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualizes the major influences during periods of development from pre-conception, through pregnancy, childhood and adolescence that affect human capital. In addition to mortality in children under five years of age, it is important to consider earlier (stillbirths) or later (from five to 20 years) loss of life. The global rate of mortality before 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with over half, including stillbirths, occurring before 28 days of age. The 1,000 days from pre-conception to two years are especially influential for human capital. The prevalence of low birth weight is high in sub-Saharan Africa and even higher in South Asia. Growth faltering, especially from birth to two years of age, occurs in most world regions while overweight increases in many regions from the pre-primary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood.The accrual of knowledge and skills is affected by health, nutrition and home resources in early childhood and by educational opportunities. Linear growth in the first two years of life better predicts intelligence quotients among adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about four years for sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving and learning until adulthood.

Published
2022

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

Author

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

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

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

Published
2021

41. Health and development from preconception to 20 years of age and human capital

Author

UCL - SSH/IACS - Institute of Analysis of Change in Contemporary and Historical Societies, Black, Robert E, Liu, Li, Hartwig, Fernando P, Villavicencio, Francisco, Rodriguez-Martinez, Andrea, Vidaletti, Luis P, Perin, Jamie, Black, Maureen M, Blencowe, Hannah, You, Danzhen, Hug, Lucia, Masquelier, Bruno, Cousens, Simon, Gove, Amber, Vaivada, Tyler, Yeung, Diana, Behrman, Jere, Martorell, Reynaldo, Osmond, Clive, Stein, Aryeh D, Adair, Linda S, Fall, Caroline H D, Horta, Bernardo, Menezes, Ana M B, Ramirez-Zea, Manuel, Richter, Linda M, Patton, George C, Bendavid, Eran, Ezzati, Majid, Bhutta, Zulfiqar A, Lawn, Joy E, Victora, Cesar G, UCL - SSH/IACS - Institute of Analysis of Change in Contemporary and Historical Societies, Black, Robert E, Liu, Li, Hartwig, Fernando P, Villavicencio, Francisco, Rodriguez-Martinez, Andrea, Vidaletti, Luis P, Perin, Jamie, Black, Maureen M, Blencowe, Hannah, You, Danzhen, Hug, Lucia, Masquelier, Bruno, Cousens, Simon, Gove, Amber, Vaivada, Tyler, Yeung, Diana, Behrman, Jere, Martorell, Reynaldo, Osmond, Clive, Stein, Aryeh D, Adair, Linda S, Fall, Caroline H D, Horta, Bernardo, Menezes, Ana M B, Ramirez-Zea, Manuel, Richter, Linda M, Patton, George C, Bendavid, Eran, Ezzati, Majid, Bhutta, Zulfiqar A, Lawn, Joy E, and Victora, Cesar G

Abstract

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5–19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Published
2022

42. Average Causal Effect Estimation Via Instrumental Variables: the No Simultaneous Heterogeneity Assumption.

Author

Hartwig, Fernando Pires, Wang, Linbo, Davey Smith, George, and Davies, Neil Martin

Abstract

Background: Instrumental variables (IVs) can be used to provide evidence as to whether a treatment X has a causal effect on an outcome Y. Even if the instrument Z satisfies the three core IV assumptions of relevance, independence, and exclusion restriction, further assumptions are required to identify the average causal effect (ACE) of X on Y. Sufficient assumptions for this include homogeneity in the causal effect of X on Y ; homogeneity in the association of Z with X ; and no effect modification. Methods: We describe the no simultaneous heterogeneity assumption, which requires the heterogeneity in the X - Y causal effect to be mean independent of (i.e., uncorrelated with) both Z and heterogeneity in the Z - X association. This happens, for example, if there are no common modifiers of the X - Y effect and the Z - X association, and the X - Y effect is additive linear. We illustrate the assumption of no simultaneous heterogeneity using simulations and by re-examining selected published studies. Results: Under no simultaneous heterogeneity, the Wald estimand equals the ACE even if both homogeneity assumptions and no effect modification (which we demonstrate to be special cases of—and therefore stronger than—no simultaneous heterogeneity) are violated. Conclusions: The assumption of no simultaneous heterogeneity is sufficient for identifying the ACE using IVs. Since this assumption is weaker than existing assumptions for ACE identification, doing so may be more plausible than previously anticipated. [ABSTRACT FROM AUTHOR]

Published
2023
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46. Population-level seropositivity trend for SARS-Cov-2 in Rio Grande do Sul, Brazil

Author

Barros, Aluísio J D, primary, Victora, Cesar G, additional, Menezes, Ana M B, additional, Horta, Bernardo L, additional, Barros, Fernando C, additional, Hartwig, Fernando P, additional, Victora, Gabriel D, additional, Vidaletti, Luis Paulo, additional, Silveira, Mariângela F, additional, Mesenburg, Marilia A, additional, Jacques, Nadège, additional, Struchiner, Cláudio J, additional, Brust, Flávia Roberta, additional, Dall’Agnol, Marinel M, additional, Delamare, Ana Paula Longaray, additional, François, Carlos Henrique R, additional, Ikeda, Maria Letícia R, additional, Pellegrini, Débora C P, additional, Reuter, Cézane Priscila, additional, Silva, Shana G da, additional, Dellagostin, Odir A, additional, and Hallal, Pedro C, additional

Published
2021
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49. Homogeneity in the Instrument-exposure Association and Point Estimation Using Binary Instrumental Variables.

Author

Hartwig, Fernando Pires, Wang, Linbo, Davey Smith, George, and Davies, Neil Martin

Abstract

Background: Interpreting instrumental variable results often requires further assumptions in addition to the core assumptions of relevance, independence, and the exclusion restriction.Methods: We assess whether instrument-exposure additive homogeneity renders the Wald estimand equal to the average derivative effect (ADE) in the case of a binary instrument and a continuous exposure.Results: Instrument-exposure additive homogeneity is insufficient for ADE identification when the instrument is binary, the exposure is continuous, and the effect of the exposure on the outcome is nonlinear on the additive scale. For a binary exposure, the exposure-outcome effect is necessarily additive linear, so the homogeneity condition is sufficient.Conclusions: For binary instruments, instrument-exposure additive homogeneity identifies the ADE if the exposure is also binary. Otherwise, additional assumptions (such as additive linearity of the exposure-outcome effect) are required. [ABSTRACT FROM AUTHOR]

Published
2022
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