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3. Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts

Author

Silventoinen, K., Jelenkovic, A., Sund, R., Latvala, A., Honda, C., Inui, F., Tomizawa, R., Watanabe, M., Sakai, N., Rebato, E., Busjahn, A., Tyler, J., Hopper, J. L., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Calais-Ferreira, L., Oliveira, V. C., Ferreira, P. H., Medda, E., Nisticò, L., Toccaceli, V., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Duncan, G. E., Buchwald, D., Tynelius, P., Rasmussen, F., Tan, Q., Zhang, D., Pang, Z., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, Anna K., Hwang, A. E., Mack, T. M., Krueger, R. F., McGue, M., Pahlen, S., Brandt, I., Nilsen, T. S., Harris, J. R., Martin, N. G., Medland, S. E., Montgomery, G. W., Willemsen, G., Bartels, M., van Beijsterveldt, C. E. M., Franz, C. E., Kremen, W. S., Lyons, M. J., Silberg, J. L., Maes, H. H., Kandler, C., Nelson, T. L., Whitfield, K. E., Corley, R. P., Huibregtse, B. M., Gatz, M., Butler, D. A., Tarnoki, A. D., Tarnoki, D. L., Park, H. A., Lee, J., Lee, S. J., Sung, J., Yokoyama, Y., Sørensen, T. I. A., Boomsma, D. I., Kaprio, J., Silventoinen, K., Jelenkovic, A., Sund, R., Latvala, A., Honda, C., Inui, F., Tomizawa, R., Watanabe, M., Sakai, N., Rebato, E., Busjahn, A., Tyler, J., Hopper, J. L., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Calais-Ferreira, L., Oliveira, V. C., Ferreira, P. H., Medda, E., Nisticò, L., Toccaceli, V., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Duncan, G. E., Buchwald, D., Tynelius, P., Rasmussen, F., Tan, Q., Zhang, D., Pang, Z., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, Anna K., Hwang, A. E., Mack, T. M., Krueger, R. F., McGue, M., Pahlen, S., Brandt, I., Nilsen, T. S., Harris, J. R., Martin, N. G., Medland, S. E., Montgomery, G. W., Willemsen, G., Bartels, M., van Beijsterveldt, C. E. M., Franz, C. E., Kremen, W. S., Lyons, M. J., Silberg, J. L., Maes, H. H., Kandler, C., Nelson, T. L., Whitfield, K. E., Corley, R. P., Huibregtse, B. M., Gatz, M., Butler, D. A., Tarnoki, A. D., Tarnoki, D. L., Park, H. A., Lee, J., Lee, S. J., Sung, J., Yokoyama, Y., Sørensen, T. I. A., Boomsma, D. I., and Kaprio, J.

Abstract

We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

Published
2020
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4. The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Author

Silventoinen, K., primary, Jelenkovic, A., additional, Yokoyama, Y., additional, Sund, R., additional, Sugawara, M., additional, Tanaka, M., additional, Matsumoto, S., additional, Bogl, L. H., additional, Freitas, D. L., additional, Maia, J. A., additional, Hjelmborg, J. v. B., additional, Aaltonen, S., additional, Piirtola, M., additional, Latvala, A., additional, Calais-Ferreira, L., additional, Oliveira, V. C., additional, Ferreira, P. H., additional, Ji, F., additional, Ning, F., additional, Pang, Z., additional, Ordoñana, J. R., additional, Sánchez-Romera, J. F., additional, Colodro-Conde, L., additional, Burt, S. A., additional, Klump, K. L., additional, Martin, N. G., additional, Medland, S. E., additional, Montgomery, G. W., additional, Kandler, C., additional, McAdams, T. A., additional, Eley, T. C., additional, Gregory, A. M., additional, Saudino, K. J., additional, Dubois, L., additional, Boivin, M., additional, Brendgen, M., additional, Dionne, G., additional, Vitaro, F., additional, Tarnoki, A. D., additional, Tarnoki, D. L., additional, Haworth, C. M. A., additional, Plomin, R., additional, Öncel, S. Y., additional, Aliev, F., additional, Medda, E., additional, Nisticò, L., additional, Toccaceli, V., additional, Craig, J. M., additional, Saffery, R., additional, Siribaddana, S. H., additional, Hotopf, M., additional, Sumathipala, A., additional, Rijsdijk, F., additional, Jeong, H.-U., additional, Spector, T., additional, Mangino, M., additional, Lachance, G., additional, Gatz, M., additional, Butler, D. A., additional, Gao, W., additional, Yu, C., additional, Li, L., additional, Bayasgalan, G., additional, Narandalai, D., additional, Harden, K. P., additional, Tucker-Drob, E. M., additional, Christensen, K., additional, Skytthe, A., additional, Kyvik, K. O., additional, Derom, C. A., additional, Vlietinck, R. F., additional, Loos, R. J. F., additional, Cozen, W., additional, Hwang, A. E., additional, Mack, T. M., additional, He, M., additional, Ding, X., additional, Silberg, J. L., additional, Maes, H. H., additional, Cutler, T. L., additional, Hopper, J. L., additional, Magnusson, P. K. E., additional, Pedersen, N. L., additional, Dahl Aslan, A. K., additional, Baker, L. A., additional, Tuvblad, C., additional, Bjerregaard-Andersen, M., additional, Beck-Nielsen, H., additional, Sodemann, M., additional, Ullemar, V., additional, Almqvist, C., additional, Tan, Q., additional, Zhang, D., additional, Swan, G. E., additional, Krasnow, R., additional, Jang, K. L., additional, Knafo-Noam, A., additional, Mankuta, D., additional, Abramson, L., additional, Lichtenstein, P., additional, Krueger, R. F., additional, McGue, M., additional, Pahlen, S., additional, Tynelius, P., additional, Rasmussen, F., additional, Duncan, G. E., additional, Buchwald, D., additional, Corley, R. P., additional, Huibregtse, B. M., additional, Nelson, T. L., additional, Whitfield, K. E., additional, Franz, C. E., additional, Kremen, W. S., additional, Lyons, M. J., additional, Ooki, S., additional, Brandt, I., additional, Nilsen, T. S., additional, Harris, J. R., additional, Sung, J., additional, Park, H. A., additional, Lee, J., additional, Lee, S. J., additional, Willemsen, G., additional, Bartels, M., additional, van Beijsterveldt, C. E. M., additional, Llewellyn, C. H., additional, Fisher, A., additional, Rebato, E., additional, Busjahn, A., additional, Tomizawa, R., additional, Inui, F., additional, Watanabe, M., additional, Honda, C., additional, Sakai, N., additional, Hur, Y.-M., additional, Sørensen, T. I. A., additional, Boomsma, D. I., additional, and Kaprio, J., additional

Published
2019
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5. The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Author

Silventoinen, K., Jelenkovic, A., Yokoyama, Y., Sund, R., Sugawara, M., Tanaka, M., Matsumoto, S., Bogl, L. H., Freitas, D. L., Maia, J. A., Hjelmborg, J. v. B., Aaltonen, S., Piirtola, M., Latvala, A., Calais-Ferreira, L., Oliveira, V. C., Ferreira, P. H., Ji, F., Ning, F., Pang, Z., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Martin, N. G., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Brendgen, M., Dionne, G., Vitaro, F., Tarnoki, A. D., Tarnoki, D. L., Haworth, C. M. A., Plomin, R., Oncel, S. Y., Aliev, F., Medda, E., Nistico, L., Toccaceli, V., Craig, J. M., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Jeong, H. -U., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Gao, W., Yu, C., Li, L., Bayasgalan, G., Narandalai, D., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Silberg, J. L., Maes, H. H., Cutler, T. L., Hopper, J. L., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, A. K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Ullemar, V., Almqvist, C., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Rasmussen, F., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Harris, J. R., Sung, J., Park, H. A., Lee, J., Lee, S. J., Willemsen, G., Bartels, M., Van Beijsterveldt, C. E. M., Llewellyn, C. H., Fisher, A., Rebato, E., Busjahn, A., Tomizawa, R., Inui, F., Watanabe, M., Honda, C., Sakai, N., Hur, Y. -M., Sørensen, T. I. A., Boomsma, D. I., Kaprio, J., Silventoinen, K., Jelenkovic, A., Yokoyama, Y., Sund, R., Sugawara, M., Tanaka, M., Matsumoto, S., Bogl, L. H., Freitas, D. L., Maia, J. A., Hjelmborg, J. v. B., Aaltonen, S., Piirtola, M., Latvala, A., Calais-Ferreira, L., Oliveira, V. C., Ferreira, P. H., Ji, F., Ning, F., Pang, Z., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Martin, N. G., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Brendgen, M., Dionne, G., Vitaro, F., Tarnoki, A. D., Tarnoki, D. L., Haworth, C. M. A., Plomin, R., Oncel, S. Y., Aliev, F., Medda, E., Nistico, L., Toccaceli, V., Craig, J. M., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Jeong, H. -U., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Gao, W., Yu, C., Li, L., Bayasgalan, G., Narandalai, D., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Silberg, J. L., Maes, H. H., Cutler, T. L., Hopper, J. L., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, A. K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Ullemar, V., Almqvist, C., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Rasmussen, F., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Harris, J. R., Sung, J., Park, H. A., Lee, J., Lee, S. J., Willemsen, G., Bartels, M., Van Beijsterveldt, C. E. M., Llewellyn, C. H., Fisher, A., Rebato, E., Busjahn, A., Tomizawa, R., Inui, F., Watanabe, M., Honda, C., Sakai, N., Hur, Y. -M., Sørensen, T. I. A., Boomsma, D. I., and Kaprio, J.

Published
2019

6. The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Author

Silventoinen, K, Jelenkovic, A, Yokoyama, Y, Sund, R, Sugawara, M, Tanaka, M, Matsumoto, S, Bogl, L H, Freitas, D L, Maia, J A, Hjelmborg, J V B, Aaltonen, S, Piirtola, M, Latvala, A, Calais-Ferreira, L, Oliveira, V C, Ferreira, P H, Ji, F, Ning, F, Pang, Z, Ordoñana, J R, Sánchez-Romera, J F, Colodro-Conde, L, Burt, S A, Klump, K L, Martin, N G, Medland, S E, Montgomery, G W, Kandler, C, McAdams, T A, Eley, T C, Gregory, A M, Saudino, K J, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Tarnoki, A D, Tarnoki, D L, Haworth, C M A, Plomin, R, Öncel, S Y, Aliev, F, Medda, E, Nisticò, L, Toccaceli, V, Craig, J M, Saffery, R, Siribaddana, S H, Hotopf, M, Sumathipala, A, Rijsdijk, F, Jeong, H-U, Spector, T, Mangino, M, Lachance, G, Gatz, M, Butler, D A, Gao, W, Yu, C, Li, L, Bayasgalan, G, Narandalai, D, Harden, K P, Tucker-Drob, E M, Christensen, K, Skytthe, A, Kyvik, K O, Derom, C A, Vlietinck, R F, Loos, R J F, Cozen, W, Hwang, A E, Mack, T M, He, M, Ding, X, Silberg, J L, Maes, H H, Cutler, T L, Hopper, J L, Magnusson, P K E, Pedersen, N L, Dahl Aslan, A K, Baker, L A, Tuvblad, C, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Ullemar, V, Almqvist, C, Tan, Q, Zhang, D, Swan, G E, Krasnow, R, Jang, K L, Knafo-Noam, A, Mankuta, D, Abramson, L, Lichtenstein, P, Krueger, R F, McGue, M, Pahlen, S, Tynelius, P, Rasmussen, F, Duncan, G E, Buchwald, D, Corley, R P, Huibregtse, B M, Nelson, T L, Whitfield, K E, Franz, C E, Kremen, W S, Lyons, M J, Ooki, S, Brandt, I, Nilsen, T S, Harris, J R, Sung, J, Park, H A, Lee, J, Lee, S J, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, C.E.M., Llewellyn, C H, Fisher, A, Rebato, E, Busjahn, A, Tomizawa, R, Inui, F, Watanabe, M, Honda, C, Sakai, N, Hur, Y-M, Sørensen, T I A, Boomsma, D.I., Kaprio, J, Silventoinen, K, Jelenkovic, A, Yokoyama, Y, Sund, R, Sugawara, M, Tanaka, M, Matsumoto, S, Bogl, L H, Freitas, D L, Maia, J A, Hjelmborg, J V B, Aaltonen, S, Piirtola, M, Latvala, A, Calais-Ferreira, L, Oliveira, V C, Ferreira, P H, Ji, F, Ning, F, Pang, Z, Ordoñana, J R, Sánchez-Romera, J F, Colodro-Conde, L, Burt, S A, Klump, K L, Martin, N G, Medland, S E, Montgomery, G W, Kandler, C, McAdams, T A, Eley, T C, Gregory, A M, Saudino, K J, Dubois, L, Boivin, M, Brendgen, M, Dionne, G, Vitaro, F, Tarnoki, A D, Tarnoki, D L, Haworth, C M A, Plomin, R, Öncel, S Y, Aliev, F, Medda, E, Nisticò, L, Toccaceli, V, Craig, J M, Saffery, R, Siribaddana, S H, Hotopf, M, Sumathipala, A, Rijsdijk, F, Jeong, H-U, Spector, T, Mangino, M, Lachance, G, Gatz, M, Butler, D A, Gao, W, Yu, C, Li, L, Bayasgalan, G, Narandalai, D, Harden, K P, Tucker-Drob, E M, Christensen, K, Skytthe, A, Kyvik, K O, Derom, C A, Vlietinck, R F, Loos, R J F, Cozen, W, Hwang, A E, Mack, T M, He, M, Ding, X, Silberg, J L, Maes, H H, Cutler, T L, Hopper, J L, Magnusson, P K E, Pedersen, N L, Dahl Aslan, A K, Baker, L A, Tuvblad, C, Bjerregaard-Andersen, M, Beck-Nielsen, H, Sodemann, M, Ullemar, V, Almqvist, C, Tan, Q, Zhang, D, Swan, G E, Krasnow, R, Jang, K L, Knafo-Noam, A, Mankuta, D, Abramson, L, Lichtenstein, P, Krueger, R F, McGue, M, Pahlen, S, Tynelius, P, Rasmussen, F, Duncan, G E, Buchwald, D, Corley, R P, Huibregtse, B M, Nelson, T L, Whitfield, K E, Franz, C E, Kremen, W S, Lyons, M J, Ooki, S, Brandt, I, Nilsen, T S, Harris, J R, Sung, J, Park, H A, Lee, J, Lee, S J, Willemsen, Gonneke, Bartels, Meike, van Beijsterveldt, C.E.M., Llewellyn, C H, Fisher, A, Rebato, E, Busjahn, A, Tomizawa, R, Inui, F, Watanabe, M, Honda, C, Sakai, N, Hur, Y-M, Sørensen, T I A, Boomsma, D.I., and Kaprio, J

Abstract

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Published
2019
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7. Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region : An individual-based pooled analysis of 40 twin cohorts

Author

Silventoinen, K., Jelenkovic, A., Sund, R., Yokoyama, Y., Hur, Y. -M, Cozen, W., Hwang, A. E., Mack, T. M., Honda, C., Inui, F., Iwatani, Y., Watanabe, M., Tomizawa, R., Pietilainen, K. H., Rissanen, A., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Piirtola, M., Aaltonen, S., Oncel, S. Y., Aliev, F., Rebato, E., Hjelmborg, J. B., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Cutler, T. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Spector, T. D., Mangino, M., Lachance, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Huibregtse, B. M., Bartels, M., Van Beijsterveldt, C. E. M., Willemsen, G., Goldberg, J. H., Rasmussen, F., Tarnoki, A. D., Tarnoki, D. L., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Hopper, J. L., Sung, J., Maes, H. H., Turkheimer, E., Boomsma, D. I., Sørensen, T. I. A., Kaprio, J., Silventoinen, K., Jelenkovic, A., Sund, R., Yokoyama, Y., Hur, Y. -M, Cozen, W., Hwang, A. E., Mack, T. M., Honda, C., Inui, F., Iwatani, Y., Watanabe, M., Tomizawa, R., Pietilainen, K. H., Rissanen, A., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Piirtola, M., Aaltonen, S., Oncel, S. Y., Aliev, F., Rebato, E., Hjelmborg, J. B., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Cutler, T. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K. E., Pedersen, N. L., Dahl Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Spector, T. D., Mangino, M., Lachance, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Huibregtse, B. M., Bartels, M., Van Beijsterveldt, C. E. M., Willemsen, G., Goldberg, J. H., Rasmussen, F., Tarnoki, A. D., Tarnoki, D. L., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Hopper, J. L., Sung, J., Maes, H. H., Turkheimer, E., Boomsma, D. I., Sørensen, T. I. A., and Kaprio, J.

Abstract

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m2)], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins ≥20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.

Published
2017
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8. The new pan-asian paan problem

Author

Mack, T M

Subjects
Betel -- Usage, Mouth cancer -- Risk factors, Taiwan -- Health aspects, South Asia -- Health aspects
Published
2001

9. A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus

Author

Cozen, W., Timofeeva, M. N., Diepstra, A., Hazelett, D., Delahaye-Sourdeix, M., Edlund, C. K., Franke, L., Rostgaard, K., Van Den Berg, D. J., Cortessis, V. K., Smedby, K. E., Glaser, S. L., Westra, H. J., Robison, L. L., Mack, T. M., Ghesquieres, H., Hwang, A. E., Nieters, A., De Sanjose, S., Lightfoot, T., Becker, N., Maynadie, M., Foretova, L., Roman, E., Benavente, Y., Rand, K. A., Nathwani, B. N., Glimelius, B., Staines, A., Boffetta, P., Link, B. K., Kiemeney, L., Ansell, S. M., Bhatia, S., Strong, L. C., Galan, P., Vatten, L., Habermann, T. M., Duell, E. J., Lake, A., Veenstra, R. N., Visser, L., Liu, Y., Urayama, K. Y., Montgomery, D., Gaborieau, V., Weiss, L. M., Byrnes, G., Lathrop, M., Cocco, P., Best, T., Skol, A. D., Adami, H. O., Melbye, M., Cerhan, J. R., Gallagher, A., Taylor, G. M., Slager, S. L., Brennan, P., Coetzee, G. A., Conti, D. V., Onel, K., Jarrett, R. F., Hjalgrim, H., Van Den Berg, A., and McKay, J. D.

Abstract

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI)=0.76-0.86, P combined =3.5 × 10 10), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Published
2014

10. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Author

Jelenkovic, A., Hur, Y. -M, Sund, R., Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, S., Heikkilä, K., Öncel, S.Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D’Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., Van Beijsterveldt, T. C., Willemsen, G., Alexandra Burt, S., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V. B., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sørensen, T. I. A., Kaprio, J., Silventoinen, K., Jelenkovic, A., Hur, Y. -M, Sund, R., Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, S., Heikkilä, K., Öncel, S.Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. -M, Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D’Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. -U, Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, Anna K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., Van Beijsterveldt, T. C., Willemsen, G., Alexandra Burt, S., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V. B., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sørensen, T. I. A., Kaprio, J., and Silventoinen, K.

Abstract

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

Published
2016
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11. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

Author

University of Helsinki, Department of Social Research, University of Helsinki, Department of Public Health, University of Helsinki, Clinicum, Jelenkovic, Aline, Hur, Yoon-Mi, Sund, Reijo, Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, Sari, Heikkilä, Kauko, Oncel, S. Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. M., Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. U., Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, A. K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., van Beijsterveldt, T. C., Willemsen, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sorensen, T. I., Kaprio, Jaakko, Silventoinen, Karri, University of Helsinki, Department of Social Research, University of Helsinki, Department of Public Health, University of Helsinki, Clinicum, Jelenkovic, Aline, Hur, Yoon-Mi, Sund, Reijo, Yokoyama, Y., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Rijsdijk, F., Tan, Q., Zhang, D., Pang, Z., Aaltonen, Sari, Heikkilä, Kauko, Oncel, S. Y., Aliev, F., Rebato, E., Tarnoki, A. D., Tarnoki, D. L., Christensen, K., Skytthe, A., Kyvik, K. O., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Ordonana, J. R., Sanchez-Romera, J. F., Colodro-Conde, L., Cozen, W., Hwang, A. E., Mack, T. M., Sung, J., Song, Y. M., Yang, S., Lee, K., Franz, C. E., Kremen, W. S., Lyons, M. J., Busjahn, A., Nelson, T. L., Whitfield, K. E., Kandler, C., Jang, K. L., Gatz, M., Butler, D. A., Stazi, M. A., Fagnani, C., D'Ippolito, C., Duncan, G. E., Buchwald, D., Derom, C. A., Vlietinck, R. F., Loos, R. J., Martin, N. G., Medland, S. E., Montgomery, G. W., Jeong, H. U., Swan, G. E., Krasnow, R., Magnusson, P. K., Pedersen, N. L., Dahl-Aslan, A. K., McAdams, T. A., Eley, T. C., Gregory, A. M., Tynelius, P., Baker, L. A., Tuvblad, C., Bayasgalan, G., Narandalai, D., Lichtenstein, P., Spector, T. D., Mangino, M., Lachance, G., Bartels, M., van Beijsterveldt, T. C., Willemsen, G., Burt, S. A., Klump, K. L., Harris, J. R., Brandt, I., Nilsen, T. S., Krueger, R. F., McGue, M., Pahlen, S., Corley, R. P., Hjelmborg, J. V., Goldberg, J. H., Iwatani, Y., Watanabe, M., Honda, C., Inui, F., Rasmussen, F., Huibregtse, B. M., Boomsma, D. I., Sorensen, T. I., Kaprio, Jaakko, and Silventoinen, Karri

Abstract

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

Published
2016

12. The CODATwins Project: the cohort description of collaborative project of development of anthropometrical measures in twins to study macro-environmental variation in genetic and environmental effects on anthropometric traits

Author

Silventoinen, K., Jelenkovic, A., Sund, R., Honda, C., Aaltonen, S., Yokoyama, Y., Tarnoki, AD, Tarnoki, D. L., Ning, F., Ji, F., Pang, Z., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Haworth, C. M. A., Plomin, R., Öncel, S. Y., Aliev, F., Stazi, M. A., Fagnani, C., D'Ippolito, C., Craig, J., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Bayasgalan, G., Narandalai, D., Freitas, D. L., Maia, J. A., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Hong, C., Chong, Y., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Chang, B., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Aujard, K., Magnusson, P. K. E., Pedersen, N. L., Aslan, A. K. D., Song, Y.- M., Yang, S., Lee, K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Heikkilä, K., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Inui, F., Watanabe, M., Bartels, M., van Beijsterveldt, T. C. E. M., Wardle, J., Llewellyn, C. H., Fisher, A., Rebato, E., Martin, N. G., Iwatani, Y., Hayakawa, K., Rasmussen, F., Sung, J., Harris, J. R., Willemsen, G., Busjahn, A., Goldberg, J. H., Boomsma, D. I., Hur, Y. - M., Sørensen, T. I. A., Kaprio, J., Silventoinen, K., Jelenkovic, A., Sund, R., Honda, C., Aaltonen, S., Yokoyama, Y., Tarnoki, AD, Tarnoki, D. L., Ning, F., Ji, F., Pang, Z., Ordoñana, J. R., Sánchez-Romera, J. F., Colodro-Conde, L., Burt, S. A., Klump, K. L., Medland, S. E., Montgomery, G. W., Kandler, C., McAdams, T. A., Eley, T. C., Gregory, A. M., Saudino, K. J., Dubois, L., Boivin, M., Haworth, C. M. A., Plomin, R., Öncel, S. Y., Aliev, F., Stazi, M. A., Fagnani, C., D'Ippolito, C., Craig, J., Saffery, R., Siribaddana, S. H., Hotopf, M., Sumathipala, A., Spector, T., Mangino, M., Lachance, G., Gatz, M., Butler, D. A., Bayasgalan, G., Narandalai, D., Freitas, D. L., Maia, J. A., Harden, K. P., Tucker-Drob, E. M., Christensen, K., Skytthe, A., Kyvik, K. O., Hong, C., Chong, Y., Derom, C. A., Vlietinck, R. F., Loos, R. J. F., Cozen, W., Hwang, A. E., Mack, T. M., He, M., Ding, X., Chang, B., Silberg, J. L., Eaves, L. J., Maes, H. H., Cutler, T. L., Hopper, J. L., Aujard, K., Magnusson, P. K. E., Pedersen, N. L., Aslan, A. K. D., Song, Y.- M., Yang, S., Lee, K., Baker, L. A., Tuvblad, C., Bjerregaard-Andersen, M., Beck-Nielsen, H., Sodemann, M., Heikkilä, K., Tan, Q., Zhang, D., Swan, G. E., Krasnow, R., Jang, K. L., Knafo-Noam, A., Mankuta, D., Abramson, L., Lichtenstein, P., Krueger, R. F., McGue, M., Pahlen, S., Tynelius, P., Duncan, G. E., Buchwald, D., Corley, R. P., Huibregtse, B. M., Nelson, T. L., Whitfield, K. E., Franz, C. E., Kremen, W. S., Lyons, M. J., Ooki, S., Brandt, I., Nilsen, T. S., Inui, F., Watanabe, M., Bartels, M., van Beijsterveldt, T. C. E. M., Wardle, J., Llewellyn, C. H., Fisher, A., Rebato, E., Martin, N. G., Iwatani, Y., Hayakawa, K., Rasmussen, F., Sung, J., Harris, J. R., Willemsen, G., Busjahn, A., Goldberg, J. H., Boomsma, D. I., Hur, Y. - M., Sørensen, T. I. A., and Kaprio, J.

Published
2015

26. Menopausal estrogen therapy and hip fractures.

Author

Paganini-Hill, Annlia, Ross, Ronald K., Gerkins, Vibeke R., Henderson, Brian E., Arthur, Mary, Mack, Thomas M., Paganini-Hill, A, Ross, R K, Gerkins, V R, Henderson, B E, Arthur, M, and Mack, T M

Subjects
HORMONE therapy for menopause, BONE fractures, OLDER women
Abstract

The association between menopausal estrogen therapy and hip fracture was studied in a retirement community. Ninety-one hip fracture cases during a 5-year period in female residents under age 80 were compared to age-and race-matched community controls. Estrogen use was recorded from the medical records of the outpatient care facility and personal interviews. The estimated risk ratio for use of oral estrogens in excess of 60 months was 0.42. This protective effect was largely limited to oophorectomized women for whom the risk ratio for a comparable duration of use was 0.14; the risk significantly decreased with increased duration, but no such trend existed with increased dosage. Diabetes mellitus, low Quetelet's index, tallness, prolonged immobilization or physical inactivity, use of corticosteroids, early age at menopause, low levels of sunlight exposure, and heavy cigarette smoking were each independent risk factors for hip fracture but none confounded the observed association with estrogen use. [ABSTRACT FROM AUTHOR]

Published
1981
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29. Epidemiology of smallpox in west Pakistan. III. Outbreak detection and interlocality transmission. 1971.

Author

Thomas, D B, Mack, T M, Ali, A, and Khan, M M

Abstract

During one year, 121 outbreaks of variola major were detected in 99 of the 1717 localities within a rural area of West Pakistan with a total population of approximately 1.2 million. Only 19% of the outbreaks, representing 36% of the 1040 investigated cases, were officially reported, although potential strengths in the government surveillance system were also identified. Persistence of smallpox within the area depended on introductions from the outside, and more than one-half of all outbreaks of known source could be ultimately traced to cities. Within the study area, outbreaks with the largest numbers of cases and those in the larger communities were the ones from which smallpox was most frequently transported. The frequency with which variola was introduced into localities was directly related to population size and to the presence of medical care facilities. Trips between localities by infected individuals were extremely rare events. They were made most often during the late fall and winter, primarily during the incubation period of the disease, and did not differ in purpose, means or destination from journeys unassociated with smallpox. Individuals at relatively high risk of becoming introducers included the unvaccinated (primarily children under five), the unschooled and those not native to the area. Vaccination priorities based on these findings could increase the efficiency of smallpox eradication efforts.

Published
1995
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30. Adenocarcinoma of the stomach and exposure to occupational dust.

Author

Wright, W E, Bernstein, L, Peters, J M, Garabrant, D H, and Mack, T M

Abstract

The authors studied 1,342 cases of adenocarcinoma of the stomach identified by a population-based cancer registry in Los Angeles County, California. The cases were males aged 20-64 years first diagnosed between 1972 and 1982. To determine whether exposure to occupational dust increased the risk of developing stomach cancer, occupational titles were rated for the likelihood of exposure to various kinds of dust. Men who worked in dusty jobs had a risk for developing stomach cancer 1.3 times that of unexposed men (95% confidence interval = 1.2-1.4). The association of exposure to dust with stomach cancer was stronger at higher levels of exposure. The risk was not uniform throughout the stomach: the highest risk (1.8 times that of unexposed men) was found for the antrum/pylorus. At that site, exposure to mineral dust carried the greatest risk for cancer (3.7 times the risk for unexposed men). The highest risks from dust exposure were observed in blacks. Risk was related to race, socioeconomic status, and immigrant status, but these factors did not entirely explain the association with dust exposure. The observed relation between dust exposure and stomach cancer is consistent with results of previous mortality and case-control studies of cancer in men who worked in dusty occupations. Ingested dust may be one factor in the etiology of adenocarcinoma of the stomach.

Published
1988
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31. Job activity and colon cancer risk.

Author

Garabrant, D H, Peters, J M, Mack, T M, and Bernstein, L

Abstract

The authors studied 2,950 population-based colon cancer cases in males in Los Angeles County, California, that were diagnosed between 1972 and 1981. To determine if colon cancer risk is reduced by physical activity on the job in males aged 20-64 years, the authors first rated each occupation by judging the activity level as high, moderate, or sedentary. Men with sedentary jobs had a colon cancer risk at least 1.6 times that of men whose jobs required a high level of activity. Risk increased in a stepwise manner as activity level decreased. This gradient was consistently seen within each socioeconomic stratum, among whites, blacks, immigrant and native Hispanics, and for each subsection of the colon from the hepatic flexure to the sigmoid. The protective effect of physical activity was very strong in the descending colon and diminished in a gradient both proximally and distally. There was no such relationship between physical activity and risk for rectal cancer. Physical activity may play a major, previously unrecognized role in colon cancer etiology. Such a role is consistent with the known pattern of colon cancer occurrence and with our understanding of colon physiology and colon cancer pathogenesis. In addition to the implications for prevention, understanding the effects of physical activity on colon cancer risk may allow future studies to evaluate more accurately the role played by diet.

Published
1984
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41. Stroke prevention and oestrogen replacement.

Author

Pike, M C, Henderson, B E, Mack, T M, Lobo, R A, and Ross, R K

Subjects
*CEREBROVASCULAR disease prevention, *MEDROXYPROGESTERONE, *CEREBROVASCULAR disease, *HIGH density lipoproteins, *HORMONES, *THERAPEUTICS, *TIME
Published
1989
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42. Stroke prevention and oestrogen replacement therapy.

Author

Ross, R K, Pike, M C, Henderson, B E, Mack, T M, and Lobo, R A

Subjects
*CEREBROVASCULAR disease prevention, *ESTROGEN replacement therapy, *CEREBROVASCULAR disease, *COMPARATIVE studies, *CAUSES of death, *HYSTERECTOMY, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *EVALUATION research
Published
1989
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43. A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Author

Cozen W, Timofeeva MN, Li D, Diepstra A, Hazelett D, Delahaye-Sourdeix M, Edlund CK, Franke L, Rostgaard K, Van Den Berg DJ, Cortessis VK, Smedby KE, Glaser SL, Westra HJ, Robison LL, Mack TM, Ghesquieres H, Hwang AE, Nieters A, de Sanjose S, Lightfoot T, Becker N, Maynadie M, Foretova L, Roman E, Benavente Y, Rand KA, Nathwani BN, Glimelius B, Staines A, Boffetta P, Link BK, Kiemeney L, Ansell SM, Bhatia S, Strong LC, Galan P, Vatten L, Habermann TM, Duell EJ, Lake A, Veenstra RN, Visser L, Liu Y, Urayama KY, Montgomery D, Gaborieau V, Weiss LM, Byrnes G, Lathrop M, Cocco P, Best T, Skol AD, Adami HO, Melbye M, Cerhan JR, Gallagher A, Taylor GM, Slager SL, Brennan P, Coetzee GA, Conti DV, Onel K, Jarrett RF, Hjalgrim H, van den Berg A, and McKay JD

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Genetic Variation, Genome-Wide Association Study, Humans, Male, Middle Aged, Young Adult, Basic Helix-Loop-Helix Transcription Factors genetics, Chromosomes, Human, Pair 19 genetics, Genetic Predisposition to Disease, Hodgkin Disease genetics
Abstract

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Published
2014
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44. Development and representativeness of a large population-based cohort of native Californian twins.

Author

Cockburn MG, Hamilton AS, Zadnick J, Cozen W, and Mack TM

Subjects
Adolescent, Adult, Age Distribution, Aged, Aged, 80 and over, Birth Certificates, California epidemiology, Censuses, Data Collection methods, Female, Humans, Male, Middle Aged, Program Evaluation, Sex Distribution, Socioeconomic Factors, Surveys and Questionnaires, Cohort Studies, Patient Selection, Twins
Abstract

We have established a large cohort of twins to facilitate studies of the role of genetics and environment in the development of disease. The cohort has been derived from all multiple births occurring in California between 1908-82 (256,616 in total). We report here on our efforts to contact these twins and their completion of a detailed 16 page risk factor questionnaire. Addresses of the individuals were obtained by linking the birth records with the California Department of Motor Vehicles (DMV) roster of licensees. To date this has been completed for twins born between 1908 and 1972 (200,589 individuals). The linkage has revealed 112,468 matches and, because of less complete DMV records in some years, was less successful in older females than in younger females and all males. Over 41,000 twins have participated by completing the questionnaire. Based on estimates of numbers of individuals receiving a questionnaire, we estimate our crude response rate to be between 42.2% and 49.6%, highest among females in their 40s (62.8%). We describe the representativeness of the twins in the original birth cohort, those identified by the linkage, and those completing the questionnaire. Compared to the 1990 resident population of California-born resident singletons, the respondents were of similar age, sex, race and residential distribution (for although we were able to locate fewer older females, they had a higher response rate), but were less likely to have been educated for more than 12 years. We provide a brief synopsis of studies nested within this cohort. We also elucidate our plans for expanding the cohort in the near future.

Published
2001
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45. High constant incidence in twins and other relatives of women with breast cancer.

Author

Peto J and Mack TM

Subjects
Adult, Age Factors, Aged, Breast Neoplasms epidemiology, Diseases in Twins epidemiology, Environment, Female, Humans, Middle Aged, Mothers, Neoplasms, Multiple Primary epidemiology, Neoplasms, Multiple Primary genetics, Nuclear Family, Prospective Studies, Risk Factors, Breast Neoplasms genetics, Diseases in Twins genetics, Twins, Monozygotic genetics
Abstract

The incidence of breast cancer rises steeply between ages 25 and 50, and more slowly thereafter. In contrast, the incidence in the unaffected (contralateral) breast of women who have had breast cancer remains constant at about 0.7% per year for at least the next 20 years after diagnosis, irrespective of age at first diagnosis. The incidence in relatives of the patients seems to show a similar pattern. The incidence in a prospective study of monozygotic twins of patients was approximately constant at 1.3% per year (77 cases), again about 0.7% per breast. At ages older than a patient's age at diagnosis, her mother and sisters have an incidence of 0.3-0.4% per year. Above the index patient's age at diagnosis, the rate in relatives shows no temporal trend and is independent of the patient's age at diagnosis. A statistically simple explanation is that incidence in susceptible women increases to a high constant level by a predetermined age that varies between families, but this seems inconsistent with conventional models of carcinogenesis and susceptibility. The very high incidence in monozygotic twins of patients indicates that a high proportion, and perhaps the majority, of breast cancers arise in a susceptible minority of women.

Published
2000
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46. Use of twins as mutual proxy respondents in a case-control study of breast cancer: effect of item nonresponse and misclassification.

Author

Hamilton AS and Mack TM

Subjects
Case-Control Studies, Humans, North America epidemiology, Odds Ratio, Reproductive History, Sensitivity and Specificity, Twins, Dizygotic statistics & numerical data, Twins, Monozygotic statistics & numerical data, Breast Neoplasms epidemiology, Data Collection methods, Diseases in Twins epidemiology, Medical History Taking methods, Mental Recall
Abstract

A case-control study of breast cancer in twins diagnosed before 1988 was used to characterize the effects on odds ratios when proxy responses from co-twins are used. North American disease-discordant pairs were ascertained through advertisements, and mailed questionnaires were returned from both members of 671 pairs and from one member of 391 pairs. Biases from the proxy response were attributed to nonresponse or misclassification. Nonresponse varied according to type of exposure variable, depth of detail requested, joint exposure status of the pair, respondent's case-control status, zygosity, and social closeness of the pair. Misclassification was minimal, generally nondifferential, and a high degree of reliability between the proxy and self-report was indicated by the kappa statistic and the intraclass correlation coefficient. By using double-respondent pairs, a method was developed to adjust proxy responses for both sources of bias. These adjustments resulted in minor changes to the odds ratios for the variables studied (age at menarche, reproductive factors, and hormone use). A larger difference was observed between the odds ratios based on all pairs and those based on double-respondent pairs only. These findings demonstrate that, for these variables in this population, twins are reliable proxies for each other and that results from single-respondent pairs should be included.

Published
2000
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47. Representativeness of a roster of volunteer North American twins with chronic disease.

Author

Mack TM, Deapen D, and Hamilton AS

Subjects
Adult, Advertising, Aged, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Chronic Disease, Demography, Diseases in Twins genetics, Female, Humans, Male, Middle Aged, Multiple Sclerosis epidemiology, Multiple Sclerosis genetics, North America epidemiology, Patient Selection, Periodicals as Topic, Risk Factors, Diseases in Twins epidemiology, Twin Studies as Topic
Abstract

To identify large numbers of twins affected by chronic disease as potential subjects for studies of environmental and genetic chronic disease determinants, we advertised for affected twins over the period 1980-91 in newspapers across North America. Responses were received from 17 245 twin pairs in which cases of cancer or other chronic disease had occurred. To assess the representativeness of affected twins identified by advertising, we evaluated the pattern of reporting, compared the cases identified to the number of cases estimated to be prevalent among all North American twins, compared the cases to population-based singleton case series, compared the healthy co-twins to population-based samples of healthy persons, assessed the impact on ascertainment of opinions about disease causation, compared the pattern of prospective to retrospective ascertainment of disease in the originally unaffected co-twins of cases, and compared the results of the prospective ascertainment of disease in co-twins to comparable published estimates. Youth, gender, zygosity, education, and disease concordance were found to be overall determinants of ascertainment. Disease-discordant DZ twins appeared to be modestly underascertained. While somewhat better educated, both concordant and discordant pairs were judged to be reasonably representative of affected non-Hispanic white North American twin pairs of comparable status, ie of comparable age, sex, race, and zygosity. If interpreted with caution, the concordance patterns of such twins can be used to generate genetic hypotheses, but should not be the basis of definitive heritability analyses. We conclude that advertising offers a method of identifying pairs of twins that can serve as subjects for studies designed to identify disease determinants.

Published
2000
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48. Impaired cytotoxic T lymphocyte activity in systemic lupus erythematosus following in vitro polyclonal T cell stimulation: a contributory role for non-T cells.

Author

Stohl W, Hamilton AS, Deapen DM, Mack TM, and Horwitz DA

Subjects
Antibodies, Monoclonal, CD28 Antigens immunology, CD3 Complex analysis, Chromium Radioisotopes, Female, Humans, In Vitro Techniques, Interleukin-10 immunology, Killer Cells, Natural immunology, Male, Neutralization Tests, T-Lymphocytes, Cytotoxic chemistry, Twins, Monozygotic, Lupus Erythematosus, Systemic immunology, Lymphocyte Activation immunology, T-Lymphocytes, Cytotoxic immunology
Abstract

To determine whether non-T cells contribute to impaired generation of nonrestricted cytotoxic T lymphocyte (CTL) activity in human SLE, peripheral blood mononuclear cells (PBMC) and sort-purified T cells from normal subjects and SLE patients were stimulated with anti-CD3 mAb, maintained in IL2, and assayed for cytolytic activity against 51Cr-labeled Daudi target cells. In addition, T cell and non-T cell fractions were isolated from nine pairs of monozygotic (MZ) twins discordant for SLE, reconstituted in a criss-cross pattern, and stimulated and assayed for cytolytic activity. Cytolytic responses were significantly lower in SLE PBMC cultures than in normal PBMC cultures. Addition of SLE serum to normal PBMC cultures did not inhibit generation of normal cytolytic responses, and neither 'resting' SLE PBMC prior to stimulation nor addition of neutralizing anti-IL10 mAb or costimulating anti-CD28 mAb restored generation of SLE cytolytic responses to normal. Nevertheless, despite the significantly greater cytolytic responses in normal PBMC cultures than in SLE PBMC cultures, cytolytic responses in normal purified T cell cultures were only modestly and insignificantly greater than those in SLE purified T cell cultures. Moreover, substitution of 'healthy' non-T cells for SLE non-T cells in four of the nine MZ twin-pairs appreciably enhanced cytolytic responses, and substitution of SLE non-T cells for 'healthy' non-T cells in five of the seven twin-pairs tested appreciably diminished cytolytic responses. Taken together, these results indicate that, in addition to any inherent SLE T cell abnormalities, impaired function of SLE non-T cells contributes to impaired generation of nonrestricted CTL activity.

Published
1999
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49. Estrogen-progestin replacement therapy and endometrial cancer.

Author

Pike MC, Peters RK, Cozen W, Probst-Hensch NM, Felix JC, Wan PC, and Mack TM

Subjects
Aged, Case-Control Studies, Drug Administration Schedule, Endometrial Neoplasms pathology, Female, Humans, Middle Aged, Neoplasm Staging, Odds Ratio, Risk, Endometrial Neoplasms chemically induced, Estrogen Replacement Therapy adverse effects, Estrogens administration & dosage, Estrogens adverse effects, Progestins administration & dosage, Progestins adverse effects
Abstract

Background: It has been known for more than 20 years that estrogen replacement therapy substantially increases a woman's risk of developing endometrial cancer. To reduce this increased risk, progestins have been added to estrogen replacement therapy for between 5 and 15 days (usually 7 or 10 days) per "month" in a sequential fashion (sequential estrogen-progestin replacement therapy) or with each dose of estrogen replacement therapy (continuous combined replacement therapy). At the present time, however, little is known about the effects of varying the number of days that progestin is used in sequential estrogen-progestin replacement therapy., Purpose: We sought to determine the effects of sequential estrogen-progestin replacement therapy and continuous combined replacement therapy on a woman's risk of developing endometrial cancer., Methods: A population-based, case-control study of 833 case subjects and 791 control subjects was conducted. Women were postmenopausal, white, and aged 50-74 years when first diagnosed with invasive endometrial cancer or were aged 50-74 years at the matching date for control subjects. All subjects were interviewed in person with the aid of a month-by-month calendar. Relative risks were estimated by odds ratios (ORs); ORs were adjusted simultaneously for the different forms of hormone replacement therapy and for the known endometrial cancer risk factors., Results: The adjusted OR was 2.17 (95% confidence interval [CI] = 1.91-2.47) per 5 years of estrogen replacement therapy use (based on 422 users among the case subjects and 262 users among the control subjects). For women who received sequential estrogen-progestin replacement therapy with the progestin given for less than 10 days (effectively 7 days) per month, the adjusted OR was only slightly reduced to 1.87 (95% CI = 1.32-2.65) per 5 years of use (74 case subjects and 47 control subjects). However, when progestin was given for 10 or more days (effectively 10 days), there was essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.82-1.41) (79 case subjects and 88 control subjects). Continuous combined replacement therapy was also associated with essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.80-1.43) (94 case subjects and 81 control subjects)., Conclusions: The progestin in sequential estrogen-progestin replacement therapy needs to be given for at least 10 days to block effectively any increased risk of endometrial cancer. Continuous combined estrogen-progestin therapy is similarly effective. Neither regimen reduces a woman's underlying risk of endometrial cancer. The sharp distinction between the effects of less than 10 days (effectively 7 days) and 10 or more days (effectively 10 days) of progestin use in sequential estrogen-progestin replacement therapy suggests that the extent of endometrial sloughing may play a critical role in determining endometrial cancer risk.

Published
1997
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50. Smoking, alcohol use, dietary factors and risk of small intestinal adenocarcinoma.

Author

Wu AH, Yu MC, and Mack TM

Subjects
Adult, Age Distribution, Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Multivariate Analysis, Adenocarcinoma etiology, Alcohol Drinking adverse effects, Feeding Behavior, Intestinal Neoplasms etiology, Intestine, Small, Smoking adverse effects
Abstract

To investigate the role of tobacco and alcohol use and dietary factors in the etiology of small intestinal adenocarcinoma, we analyzed data from a large population-based case-control study of multi-site cancers conducted in Los Angeles County between 1975 and 1984. The present analysis included interview information on 36 small intestinal adenocarcinoma patients and 998 population controls. After adjusting for age and ethnicity, men who smoked more than 100 cigarettes during their lifetimes were at a non-significantly 3-fold increased risk for small intestinal adenocarcinoma; this association was substantially weaker in women. In men and women combined, a significant 3-fold increased risk in heavy drinkers (80+ g ethanol/day) relative to more moderate drinkers and non-drinkers was observed. Although frequent (>6 times vs. less than 2 times of intake a week) intake of foods rich in heterocyclic aromatic amines (based on the combined intake of fried bacon and ham, barbecued and/or smoked meat and smoked fish) was associated with a significant 4.5-fold increased risk of small intestinal adenocarcinoma in men; this association was not present in women. Based on 2 questions that provided a crude assessment of sugar intake, risk of small intestinal adenocarcinoma in men and women appeared to be associated with adding sugar regularly in coffee or tea and daily intake of non-diet carbonated soft drinks. When we computed total sugar intake from tea, coffee and non-diet carbonated soft drinks, there was a consistent and significant trend of increasing sugar intake and risk of small intestinal adenocarcinomas. Compared with the lowest intake level a day (<5 g), medium (5-25 g) and high intakes (>25 g) were associated with ORs of 2.5 and 3.8, respectively.

Published
1997
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