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Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T, et al. Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. Psychol Med. 2013;43:47181.

Article CAS PubMed Google Scholar

Lim GY, Tam WW, Lu Y, Ho CS, Zhang MW, Ho RC. Prevalence of depression in the community from 30 countries between 1994 and 2014. Sci Rep. 2018;8:110.

Article Google Scholar

Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). Jama. 2003;289:3095105.

Article PubMed Google Scholar

Smith K. Mental health: a world of depression. Nature. 2014;515:1801.

Article CAS Google Scholar

Choi KW, Stein MB, Nishimi KM, Ge T, Coleman JR, Chen C-Y, et al. An exposure-wide and Mendelian randomization approach to identifying modifiable factors for the prevention of depression. Am J Psychiatry. 2020;177:94454.

Article PubMed PubMed Central Google Scholar

Whisman MA, Sbarra DA, Beach SR. Intimate relationships and depression: searching for causation in the sea of association. Annu Rev Clin Psychol. 2021;17:23358.

Article PubMed Google Scholar

Choi KW, Chen C-Y, Stein MB, Klimentidis YC, Wang M-J, Koenen KC, et al. Assessment of bidirectional relationships between physical activity and depression among adults: a 2-sample mendelian randomization study. JAMA Psychiatry. 2019;76:399408.

Article PubMed PubMed Central Google Scholar

Herrman H, Patel V, Kieling C, Berk M, Buchweitz C, Cuijpers P, et al. Time for united action on depression: a LancetWorld psychiatric association commission. Lancet. 2022;399:9571022.

Article PubMed Google Scholar

Cacioppo S, Grippo AJ, London S, Goossens L, Cacioppo JT. Loneliness: clinical import and interventions. Perspect Psychol Sci. 2015;10:23849.

Article PubMed PubMed Central Google Scholar

Cacioppo, JT & Patrick, W. Loneliness: human nature and the need for social connection. New York: WW Norton & Company; 2008.

Beutel ME, Klein EM, Brhler E, Reiner I, Jnger C, et al. Loneliness in the general population: prevalence, determinants and relations to mental health. BMC Psychiatry. 2017;17:97.

Article PubMed PubMed Central Google Scholar

Holt-Lunstad J, Robles TF, Sbarra DA. Advancing social connection as a public health priority in the United States. Am Psychol. 2017;72:51730.

Article PubMed PubMed Central Google Scholar

Killgore WD, Cloonan SA, Taylor EC, Dailey NS. Loneliness: a signature mental health concern in the era of COVID-19. Psychiatry Res. 2020;290:113117.

Article CAS PubMed PubMed Central Google Scholar

Bu F, Steptoe A, Fancourt D. Loneliness during a strict lockdown: trajectories and predictors during the COVID-19 pandemic in 38,217 United Kingdom adults. Soc Sci Med. 2020;265:113521.

Article PubMed PubMed Central Google Scholar

Office of the Surgeon General. Our Epidemic of Loneliness and Isolation: The U.S. Surgeon Generals Advisory on the Health Efffects of Social Connection and Community. (2023).

Holt-Lunstad J, Perissinotto C. Social isolation and loneliness as medical issues. N Engl J Med. 2023;388:1935.

Article PubMed Google Scholar

Erzen E, ikrikci . The effect of loneliness on depression: a meta-analysis. Int J Soc Psychiatry. 2018;64:42735.

Article PubMed Google Scholar

VanderWeele TJ, Tchetgen EJT, Cornelis M, Kraft P. Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age. Epidemiol Psychiatr Sci. 2018;27:26677. (2014).

Article Google Scholar

Heinrich LM, Gullone E. The clinical significance of loneliness: a literature review. Clin Psychol Rev. 2006;26:695718.

Article PubMed Google Scholar

Cacioppo JT, Hawkley LC, Thisted RA. Perceived social isolation makes me sad: 5-year cross-lagged analyses of loneliness and depressive symptomatology in the Chicago Health, aging, and social relations study. Psychol Aging. 2010;25:45363.

Article PubMed PubMed Central Google Scholar

Ebrahim S, Davey Smith G. Mendelian randomization: can genetic epidemiology help redress the failures of observational epidemiology? Hum Genet. 2008;123:1533.

Article PubMed Google Scholar

Yang YC, Boen C, Gerken K, Li T, Schorpp K, Harris KM. Social relationships and physiological determinants of longevity across the human life span. Proc Natl Acad Sci. 2016;113:57883.

Article CAS PubMed PubMed Central Google Scholar

Murthy, VH & Murthy, VH. Together. New York: Harper Collins Publishers; 2020.

Turkheimer, E & Harden, K. Behavior genetic research methods: testing quasi-causal hypotheses using multivariate twin data. In: Reis, HT & Judd, CM, editors. Handbook of research methods in personality and social psychology. New York; Cambridge University Press 2014.159-87.

Davey Smith G, Ebrahim S. Mendelian randomization: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32:122.

Article Google Scholar

Matthews T, Danese A, Wertz J, Odgers CL, Ambler A, Moffitt TE, et al. Social isolation, loneliness and depression in young adulthood: a behavioural genetic analysis. Soc Psychiatry Psychiatr Epidemiol. 2016;51:33948.

Article PubMed PubMed Central Google Scholar

Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23:R89R98.

Article CAS PubMed PubMed Central Google Scholar

Sanderson E, Glymour MM, Holmes MV, Kang H, Morrison J, Munaf MR, et al. Mendelian randomization. Nat Rev Methods Prim. 2022;2:6.

Article CAS Google Scholar

Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:113363.

Article PubMed Google Scholar

Rdevand L, Bahrami S, Frei O, Lin A, Gani O, Shadrin A, et al. Polygenic overlap and shared genetic loci between loneliness, severe mental disorders, and cardiovascular disease risk factors suggest shared molecular mechanisms. Transl Psychiatry. 2021;11:111.

Article Google Scholar

Abdellaoui A, Sanchez-Roige S, Sealock J, Treur JL, Dennis J, Fontanillas P, et al. Phenome-wide investigation of health outcomes associated with genetic predisposition to loneliness. Hum Mol Genet. 2019;28:385365.

Article CAS PubMed PubMed Central Google Scholar

Sbarra, DA. Social integration and sleep disturbance: a gene-environment interaction study. Collabra. 2016;2:1.

Abdellaoui A, Chen HY, Willemsen G, Ehli EA, Davies GE, Verweij KJ, et al. Associations between loneliness and personality are mostly driven by a genetic association with neuroticism. J Personal. 2019;87:38697.

Article Google Scholar

Boomsma DI, Cacioppo JT, Muthn B, Asparouhov T, Clark S. Longitudinal genetic analysis for loneliness in Dutch twins. Twin Res Hum Genet. 2007;10:26773.

Article PubMed Google Scholar

Wootton RE, Greenstone HS, Abdellaoui A, Denys D, Verweij KJ, Munaf MR, et al. Bidirectional effects between loneliness, smoking and alcohol use: evidence from a Mendelian randomization study. Addiction. 2021;116:4006.

Article PubMed Google Scholar

Day FR, Ong KK, Perry JR. Elucidating the genetic basis of social interaction and isolation. Nat Commun. 2018;9:16.

Article Google Scholar

Goossens L, Van Roekel E, Verhagen M, Cacioppo JT, Cacioppo S, Maes M, et al. The genetics of loneliness: linking evolutionary theory to genome-wide genetics, epigenetics, and social science. Perspect Psychol Sci. 2015;10:21326.

Article PubMed Google Scholar

Burgess S, Smith GD, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations: update for summer 2023. Wellcome Open Res. 2023;4:186.

Morrison J, Knoblauch N, Marcus JH, Stephens M, He X. Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics. Nat Genet. 2020;52:7407.

Article CAS PubMed PubMed Central Google Scholar

Wray NR, Ripke S, Mattheisen M, Trzaskowski M, Byrne EM, Abdellaoui A, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018;50:66881.

Article CAS PubMed PubMed Central Google Scholar

Levey, DF, Stein, MB, Wendt, FR, Pathak, GA, Zhou, H, Aslan, M, et al. Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in > 1.2 million individuals highlight new therapeutic directions. Nat Neurosci. 2021;7:110.

Elsworth, BL, Lyon, MS, Alexander, T, Liu, Y, Matthews, P, Hallett, J, et al. The MRC IEU OpenGWAS data infrastructure. bioRxiv (2020).

Gaziano JM, Concato J, Brophy M, Fiore L, Pyarajan S, Breeling J, et al. Million Veteran Program: a mega-biobank to study genetic influences on health and disease. J Clin Epidemiol. 2016;70:21423.

Article PubMed Google Scholar

Lwe B, Kroenke K, Grfe K. Detecting and monitoring depression with a two-item questionnaire (PHQ-2). J Psychosom Res. 2005;58:16371.

Article PubMed Google Scholar

VanderWeele TJ, Tchetgen EJT, Cornelis M, Kraft P. Methodological challenges in mendelian randomization. Epidemiology. 2014;25:42735.

Article PubMed PubMed Central Google Scholar

Verbanck M, Chen C-Y, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:6938.

Article CAS PubMed PubMed Central Google Scholar

Burgess S, Thompson SG. Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol. 2015;181:25160.

Article PubMed PubMed Central Google Scholar

Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44:51225.

Article PubMed PubMed Central Google Scholar

Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32:37789.

Article PubMed PubMed Central Google Scholar

Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40:30414.

Article PubMed PubMed Central Google Scholar

Zhao Q, Wang J, Hemani G, Bowden J, Small DS. Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score. Ann Stat. 2020;48:174269.

Article Google Scholar

Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan NA, Thompson JR. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: the role of the I 2 statistic. Int J Epidemiol. 2016;45:196174.

PubMed PubMed Central Google Scholar

Hemani G, Bowden J, Davey Smith G. Evaluating the potential role of pleiotropy in Mendelian randomization studies. Hum Mol Genet. 2018;27:R195R208.

Article CAS PubMed PubMed Central Google Scholar

Cacioppo JT, Hughes ME, Waite LJ, Hawkley LC, Thisted RA. Loneliness as a specific risk factor for depressive symptoms: cross-sectional and longitudinal analyses. Psychol Aging. 2006;21:14051.

Article PubMed Google Scholar

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