Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-26T20:24:32.575Z Has data issue: false hasContentIssue false

Chapter 4 - The Genomics of Cognitive Aging in Social Isolation

from Part I - Approaches to Society within the Brain

Published online by Cambridge University Press:  28 September 2023

By
Sung-Ha Lee  and
Seyul Kwak
Edited by
Jeanyung Chey
Jeanyung Chey
Affiliation:
Seoul National University
Get access

Summary

Loneliness is a complex trait that has been linked to negative mental and physical health outcomes, including cognitive impairment. With mounting efforts to examine the underlying mechanisms of the link between loneliness and health, recent genomics studies suggest genetic predispositions associated with social isolation and cognitive functions. Ongoing genome-wide association studies (GWASs) have identified several genetic loci linked to age-related neuropathological conditions, including the apolipoprotein E (APOE e4) allele. Moreover, emerging evidence suggests genetic influences on loneliness and social integration. In addition to the genetic factors, social genomic research suggests altered gene expression patterns under social isolation or neurodegenerative diseases; for example, chronic loneliness triggers less effective immune response gene expression patterns (conserved transcriptional response to adversity [CTRA]) in white blood cells. Moreover, a recent transcriptional analysis reported altered gene expression patterns associated with myelination in the prefrontal cortex of patients with Alzheimer’s disease. These genomics studies not only suggest that loneliness and neuropathological processes are polymorphic heritable traits but also that genetic variants interact with environmental factors regulating gene expressions on the transcriptional level. This chapter focuses on social genomics research that investigates the favorable social conditions (e.g., social integration) linked to altering gene expression profiles.

Keywords

genetic variantssingle nucleotide polymorphism (SNP)genome-wide association study (GWAS)conserved transcriptional response to adversity (CTRA)lonelinessAlzheimer’s diseasesocial genomicspurpose in lifepolygenic score (PGS)
Type
Chapter
Information
Society within the Brain
How Social Networks Interact with Our Brain, Behavior and Health as We Age
 , pp. 105 - 116
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdellaoui, A., Nivard, M. G., Hottenga, J. J., Fedko, I., Verweij, K. J. H., Baselmans, B. M. L., Ehli, E. A., Davies, G. E., Bartels, M., Boomsma, D. I., & Cacioppo, J. T. (2018). Predicting loneliness with polygenic scores of social, psychological and psychiatric traits. Genes, Brain and Behavior, 17(6). https://doi.org/10.1111/gbb.12472Google Scholar
Abdellaoui, A., Sanchez-Roige, S., Sealock, J., Treur, J. L., Dennis, J., Fontanillas, P., Elson, S., The 23andme Research Team, Nivard, M. G., Ip, H. F., van der Zee, M., Baselmans, B. M. L., Hottenga, J. J., Willemsen, G., Mosing, M., Lu, Y., Pedersen, N. L., Denys, D., Amin, N., … Boomsma, D. I. (2019). Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness. Human Molecular Genetics, 28(22), 3853–3865. https://doi:10.1093/hmg/ddz219Google Scholar
Apostolova, L. G., Risacher, S. L., Duran, T., Stage, E. C., Goukasian, N., West, J. D., Do, T. M., Grotts, J., Wilhalme, H., Nho, K., Phillips, M., Elashoff, D., & Saykin, A. J. (2018). Associations of the top 20 Alzheimer disease risk variants with brain amyloidosis. JAMA Neurology, 75(3), 328–341. https://doi.org/10.1001/jamaneurol.2017.4198CrossRefGoogle ScholarPubMed
Boomsma, D. I., Willemsen, G., Dolan, C. V., Hawkley, L. C., & Cacioppo, J. T. (2005). Genetic and environmental contributions to loneliness in adults: The Netherlands Twin Register study. Behavior Genetics, 35(6), 745–752. https://doi.org/10.1007/s10519–005-6040-8CrossRefGoogle ScholarPubMed
Boyle, P. A., Buchman, A. S., Barnes, L. L., & Bennett, D. A. (2010). Effect of a purpose in life on risk of incident Alzheimer disease and mild cognitive impairment in community-dwelling older persons. Archives of General Psychiatry, 67(3), 304–310.CrossRefGoogle ScholarPubMed
Branigan, A. R., McCallum, K. J., & Freese, J. (2013). Variation in the heritability of educational attainment: An international meta-analysis. Social Forces, 92(1), 109–140. https://doi.org/10.1093/sf/sot076Google Scholar
Christakis, N. A., & Fowler, J. H. (2014). Friendship and natural selection. PNAS, 111 (supplement_3), 10796–10801.Google Scholar
Chung, J., Wang, X., Maruyama, T., Ma, Y., Zhang, X., Mez, J., Sherva, R., Takeyama, H., Lunetta, K. L., Farrer, L. A., & Jun, G. R. (2018). Genome-wide association study of Alzheimer’s disease endophenotypes at prediagnosis stages. Alzheimer’s and Dementia, 14(5), 623–633. https://doi.org/10.1016/j.jalz.2017.11.006Google Scholar
Cole, S. W. (2014). Human Social Genomics. PLoS Genetics, 10(8). https://doi.org/10.1371/journal.pgen.1004601Google Scholar
Cole, S. W. (2019). The Conserved transcriptional response to adversity. Current Opinion in Behavioral Sciences, 28, 31–37. https://doi.org/10.1016/j.cobeha.2019.01.008CrossRefGoogle ScholarPubMed
Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007). Social regulation of gene expression in human leukocytes. Genome Biology, 8(9), R189. https://doi.org/10.1186/gb-2007-8-9-r189Google Scholar
Cole, S. W., Levine, M. E., Arevalo, J. M. G., Ma, J., Weir, D. R., & Crimmins, E. M. (2015). Loneliness, eudaimonia, and the human conserved transcriptional response to adversity. Psychoneuroendocrinology, 62, 11–17. https://doi.org/10.1016/j.psyneuen.2015.07.001Google Scholar
Deary, I. J., & Johnson, W. (2010). Intelligence and education: Causal perceptions drive analytic processes and therefore conclusions. International Journal of Epidemiology, 39(5), 1362–1369. https://doi.org/10.1093/ije/dyq072Google Scholar
Desikan, R. S., Fan, C.-C., Wang, Y., Schork, A. J., Cabral, H. J., Cupples, L. A., Thompson, W. K., Besser, L., Kukull, W. A., Holland, D., Chen, C.-H., Brewer, J. B., Karow, D. S., Kauppi, K., Witoelar, A., Karch, C. M., Bonham, L. W., Yokoyama, J. S., Rosen, H. J., … Dale, A. M. (2017). Genetic assessment of age-associated Alzheimer disease risk: Development and validation of a polygenic hazard score. PLoS Medicine, 14(3), e1002258.CrossRefGoogle ScholarPubMed
Ferencz, B., Laukka, E. J., Welmer, A. K., Kalpouzos, G., Angleman, S., Keller, L., Graff, C., Lövdén, M., & Bäckman, L. (2014). The benefits of staying active in old age: Physical activity counteracts the negative influence of PICALM, BIN1, and CLU risk alleles on episodic memory functioning. Psychology and Aging, 29(2), 440–449. https://doi.org/10.1037/a0035465Google Scholar
Fowler, J. H., Dawes, C. T., & Christakis, N. A. (2009). Model of genetic variation in human social networks. Proceedings of the National Academy of Sciences, 106(6), 1720–1724. https://doi.org/10.1073/pnas.0806746106CrossRefGoogle ScholarPubMed
Fowler, J. H., Settle, J. E., & Christakis, N. A. (2011). Correlated genotypes in friendship networks. Proceedings of the National Academy of Sciences, 108(5), 1993–1997. https://doi.org/10.1073/pnas.1011687108CrossRefGoogle ScholarPubMed
Fredrickson, B. L., Grewen, K. M., Coffey, K. A., Algoe, S. B., Firestine, A. M., Arevalo, J. M. G., & Cole, S. W. (2013). A functional genomic perspective on human well-being. Proceedings of the National Academy of Sciences, 110 (33), 13684–13689. https://doi.org/10.1073/pnas.1305419110Google Scholar
Gao, J., Davis, L. K., Hart, A. B., Sanchez-Roige, S., Han, L., Cacioppo, J. T., & Palmer, A. A. (2017). Genome-wide association study of loneliness demonstrates a role for common variation. Neuropsychopharmacology, 42(4), 811–821. https://doi.org/10.1038/npp.2016.197Google Scholar
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., … Silverberg, N. (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s and Dementia, 14(4), 535–562. https://doi.org/10.1016/j.jalz.2018.02.018CrossRefGoogle Scholar
Jiang, Y., Cui, M., Tian, W., Zhu, S., Chen, J., Suo, C., Liu, Z., Lu, M., Xu, K., Fan, M., Wang, J., Dong, Q., Ye, W., Jin, L., & Chen, X. (2021). Lifestyle, multi-omics features, and preclinical dementia among Chinese: The Taizhou Imaging Study. Alzheimer’s and Dementia. https://doi.org/10.1002/alz.12171Google Scholar
Kandel, D. B. (1978). Homophily, selection, and socialization in adolescent friendships. American Journal of Sociology, 84(2), 427–436. https://doi.org/10.1086/226792Google Scholar
Kim, Y., Cole, S. W., Carver, C. S., Antoni, M. H., & Penedo, F. J. (2021). Only the lonely: Expression of proinflammatory genes through family cancer caregiving experiences. Psychosomatic Medicine, 83(2), 149–156. https://doi.org/10.1097/PSY.0000000000000897Google Scholar
Kohrt, B. A., Worthman, C. M., Adhikari, R. P., Luitel, N. P., Arevalo, J. M. G., Ma, J., McCreath, H., Seeman, T. E., Crimmins, E. M., & Cole, S. W. (2016). Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers. Proceedings of the National Academy of Sciences, 113(29), 8156–8161. https://doi.org/10.1073/pnas.1601301113Google Scholar
Lee, J. J., Wedow, R., Okbay, A., Kong, E., Maghzian, O., Zacher, M., Nguyen-Viet, T. A., Bowers, P., Sidorenko, J., Karlsson Linnér, R., Fontana, M. A., Kundu, T., Lee, C., Li, H., Li, R., Royer, R., Timshel, P. N., Walters, R. K., Willoughby, E. A., … Cesarini, D. (2018). Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nature Genetics, 50(8), 1112–1121.Google Scholar
Lee, S. H., Choi, I., Choi, E., Lee, M., Kwon, Y., Oh, B., & Cole, S. W. (2020). Psychological well-being and gene expression in Korean adults: The role of age. Psychoneuroendocrinology, 120, 104785. https://doi.org/10.1016/j.psyneuen.2020.104785Google Scholar
Lin, C.-H., Lin, E., and Lane, H.-Y., (2017) Genetic Biomarkers on age-related cognitive decline. Frontiers in Psychiatry 8. https://doi.org/10.3389/fpsyt.2017.00247Google Scholar
Martin, A. R., Gignoux, C. R., Walters, R. K., Wojcik, G. L., Neale, B. M., Gravel, S., Daly, M. J., Bustamante, C. D., & Kenny, E. E. (2017). Human demographic history impacts genetic risk prediction across diverse populations. American Journal of Human Genetics, 100(4), 635–649. https://doi.org/10.1016/j.ajhg.2017.03.004Google Scholar
McPherson, M., Smith-Lovin, L., & Cook, J. M. (2001). Birds of a feather: Homophily in social networks. Annual Review of Sociology, 27, 415–444.Google Scholar
Mostafavi, H., Harpak, A., Agarwal, I., Conley, D., Pritchard, J. K., & Przeworski, M. (2020). Variable prediction accuracy of polygenic scores within an ancestry group. ELife, 9, e48376 https://doi.org/10.7554/eLife.48376Google Scholar
Mukherjee, S., Mez, J., Trittschuh, E., Saykin, A. J., Gibbons, L. E., Fardon, D. W., Wessels, M., Bauman, J., Moore, M., Choi, S.-E., Gross, A. L., Rich, J., Louden, D. K. N., Sanders, R. E., Grabowski, T. J., Bird, T. J., McCurry, S. M., Snitz, B. E., Kamboh, M. I., … Crane, P. K. (2020). Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups. Molecular Psychiatry 25, 2942–2951. https://doi.org/10.1038/s41380-018-0298-8Google Scholar
Murray, D. R., Haselton, M. G., Fales, M., & Cole, S. W. (2019). Subjective social status and inflammatory gene expression. Health Psychology, 38(2), 182–186. https://doi.org/10.1037/hea0000705Google Scholar
Nelson-Coffey, S. K., Fritz, M. M., Lyubomirsky, S., & Cole, S. W. (2017). Kindness in the blood: A randomized controlled trial of the gene regulatory impact of prosocial behavior. Psychoneuroendocrinology, 81, 8–13.Google Scholar
Okbay, A., Beauchamp, J. P., Fontana, M. A., Lee, J. J., Pers, T. H., Rietveld, C. A., Turley, P., Chen, G. B., Emilsson, V., Meddens, S. F. W., Oskarsson, S., Pickrell, J. K., Thom, K., Timshel, P., De Vlaming, R., Abdellaoui, A., Ahluwalia, T. S., Bacelis, J., Baumbach, C., … Benjamin, D. J. (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature, 533, 539–542. https://doi.org/10.1038/nature17671CrossRefGoogle ScholarPubMed
Raz, N., & Lustig, C. (2014). Genetic variants and cognitive aging: Destiny or a nudge? Psychology and Aging, 29(2), 359–362. https://doi.org/10.1037/a0036893Google Scholar
Seeman, T., Merkin, S. S., Goldwater, D., & Cole, S. W. (2019). Intergenerational mentoring, eudaimonic well-being and gene regulation in older adults: A pilot study. Psychoneuroendocrinology, 111, 104468.Google Scholar
Slavich, G. M., & Cole, S. W. (2013). The emerging field of human social genomics. Clinical Psychological Science, 1(3), 331–348. https://doi.org/10.1177/2167702613478594Google Scholar
Sloan, E. K., Capitanio, J. P., Tarara, R. P., Mendoza, S. P., Mason, W. A., & Cole, S. W. (2007). Social stress enhances sympathetic innervation of primate lymph nodes: Mechanisms and implications for viral pathogenesis. Journal of Neuroscience, 27(33), 8857–8865. https://doi.org/10.1523/JNEUROSCI.1247-07.2007CrossRefGoogle ScholarPubMed
Thames, A. D., Irwin, M. R., Breen, E. C., & Cole, S. W. (2019). Experienced discrimination and racial differences in leukocyte gene expression. Psychoneuroendocrinology, 106, 277–283. https://doi.org/10.1016/j.psyneuen.2019.04.016Google Scholar
Turkheimer, E., Haley, A., Waldron, M., D’Onofrio, B., & Gottesman, I. I. (2003). Socioeconomic status modifies heritability of IQ in young children. Psychological Science, 14(6), 623–628. https://doi.org/10.1046/j.0956-7976.2003.psci_1475.xGoogle Scholar
Uchida, Y., Kitayama, S., Akutsu, S., Park, J., & Cole, S. W. (2018). Optimism and the conserved transcriptional response to adversity. Health Psychology, 37(11), 1077–1080.Google Scholar
Waaktaar, T., & Torgersen, S. (2012). Genetic and environmental causes of variation in perceived loneliness in young people. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 159B(5), 580–588. https://doi.org/10.1002/ajmg.b.32064Google Scholar
Wingo, T. S., Lah, J. J., Levey, A. I., & Cutler, D. J. (2012). Autosomal recessive causes likely in early-onset Alzheimer disease. Archives of Neurology, 69(1), 59–64. https://doi.org/10.1001/archneurol.2011.221Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×