{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T06:03:25Z","timestamp":1781849005170,"version":"3.54.5"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Liaison Committee for Education, Research and Innovation in Central Norway","award":["90057601"],"award-info":[{"award-number":["90057601"]}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["250335"],"award-info":[{"award-number":["250335"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["295989"],"award-info":[{"award-number":["295989"]}],"id":[{"id":"10.13039\/501100005416","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MC_UU_00011\/1"],"award-info":[{"award-number":["MC_UU_00011\/1"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Obesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>A total of 67,110 individuals aged 13\u201380 years in the Nord-Tr\u00f8ndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Tr\u00f8ndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI \u2265 30 kg\/m<jats:sup>2<\/jats:sup>) and severe obesity (BMI \u2265 35 kg\/m<jats:sup>2<\/jats:sup>).<\/jats:p>\n<jats:p>The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, <jats:italic>p<\/jats:italic> &lt; 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, <jats:italic>p<\/jats:italic> &lt; 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, <jats:italic>p<\/jats:italic> &lt; 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, <jats:italic>p<\/jats:italic> &lt; 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date of genetic testing for the older cohorts and that we apply a contemporary genetic score to past time periods. Future research should validate our findings using a polygenic risk score constructed from historical data.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In the context of increasingly obesogenic changes in our environment over 6 decades, our findings reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. Our results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors. While it may be possible to identify those most susceptible to environmental change, who thus have the most to gain from preventive measures, efforts to reverse the obesogenic environment will benefit the whole population and help resolve the obesity epidemic.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1003452","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T18:23:59Z","timestamp":1607970239000},"page":"e1003452","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study)"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3916-7313","authenticated-orcid":true,"given":"Maria","family":"Brandkvist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-2954","authenticated-orcid":true,"given":"Johan H\u00e5kon","family":"Bj\u00f8rngaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-8881","authenticated-orcid":true,"given":"R\u00f8nnaug Astri","family":"\u00d8deg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3058-1059","authenticated-orcid":true,"given":"Ben","family":"Brumpton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1407-8314","authenticated-orcid":true,"given":"George Davey","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3837-2101","authenticated-orcid":true,"given":"Bj\u00f8rn Olav","family":"\u00c5svold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-5139","authenticated-orcid":true,"given":"Erik R.","family":"Sund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-917X","authenticated-orcid":true,"given":"Kirsti","family":"Kval\u00f8y","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristen J.","family":"Willer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1552-5291","authenticated-orcid":true,"given":"Gunnhild \u00c5berge","family":"Vie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"issue":"4","key":"pmed.1003452.ref001","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3122\/jabfm.2018.04.180008","article-title":"Multimorbidity Trends in United States Adults, 1988\u20132014","volume":"31","author":"DE King","year":"2018","journal-title":"J Am Board Fam Med"},{"issue":"3","key":"pmed.1003452.ref002","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/erv.2503","article-title":"The Prevalence of Past 12-Month and Lifetime DSM-IV Eating Disorders by BMI Category in US Men and Women","volume":"25","author":"AE Duncan","year":"2017","journal-title":"Eur Eat Disord Rev"},{"issue":"9765","key":"pmed.1003452.ref003","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0140-6736(10)62037-5","article-title":"National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants","volume":"377","author":"MM Finucane","year":"2011","journal-title":"Lancet"},{"issue":"3","key":"pmed.1003452.ref004","doi-asserted-by":"crossref","first-page":"e20173459","DOI":"10.1542\/peds.2017-3459","article-title":"Prevalence of Obesity and Severe Obesity in US Children, 1999\u20132016","volume":"141","author":"AC Skinner","year":"2018","journal-title":"Pediatrics"},{"issue":"11","key":"pmed.1003452.ref005","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1038\/s41591-019-0644-7","article-title":"Understanding the rise of cardiometabolic diseases in low- and middle-income countries","volume":"25","author":"JJ Miranda","year":"2019","journal-title":"Nat Med"},{"key":"pmed.1003452.ref006","article-title":"Recovery of trait heritability from whole genome sequence data","author":"P Wainschtein","year":"2019","journal-title":"bioRxiv"},{"issue":"1","key":"pmed.1003452.ref007","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/obr.12604","article-title":"Ethnic and population differences in the genetic predisposition to human obesity","volume":"19","author":"C Stryjecki","year":"2018","journal-title":"Obes Rev"},{"issue":"1","key":"pmed.1003452.ref008","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1001\/jama.2016.8729","article-title":"Association of a Genetic Risk Score With Body Mass Index Across Different Birth Cohorts","volume":"316","author":"S Walter","year":"2016","journal-title":"JAMA"},{"key":"pmed.1003452.ref009","doi-asserted-by":"crossref","first-page":"l4067","DOI":"10.1136\/bmj.l4067","article-title":"Quantifying the impact of genes on body mass index during the obesity epidemic: longitudinal findings from the HUNT Study","volume":"366","author":"M Brandkvist","year":"2019","journal-title":"BMJ"},{"issue":"3","key":"pmed.1003452.ref010","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cell.2019.03.028","article-title":"Polygenic Prediction of Weight and Obesity Trajectories from Birth to Adulthood","volume":"177","author":"AV Khera","year":"2019","journal-title":"Cell"},{"issue":"7538","key":"pmed.1003452.ref011","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology","volume":"518","author":"AE Locke","year":"2015","journal-title":"Nature"},{"issue":"10026","key":"pmed.1003452.ref012","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0140-6736(16)30054-X","article-title":"Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19\u00b72 million participants","volume":"387","year":"2016","journal-title":"Lancet"},{"issue":"3","key":"pmed.1003452.ref013","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/sj.ijo.0801135","article-title":"Epidemic obesity: are genetic factors involved via increased rates of assortative mating?","volume":"24","author":"J Hebebrand","year":"2000","journal-title":"Int J Obes Relat Metab Disord"},{"issue":"1","key":"pmed.1003452.ref014","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1038\/s41467-020-17117-4","article-title":"Avoiding dynastic, assortative mating, and population stratification biases in Mendelian randomization through within-family analyses","volume":"11","author":"B Brumpton","year":"2020","journal-title":"Nature communications"},{"issue":"6374","key":"pmed.1003452.ref015","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1126\/science.aan6877","article-title":"The nature of nurture: Effects of parental genotypes","volume":"359","author":"A Kong","year":"2018","journal-title":"Science"},{"issue":"16","key":"pmed.1003452.ref016","doi-asserted-by":"crossref","first-page":"eaay0328","DOI":"10.1126\/sciadv.aay0328","article-title":"Population phenomena inflate genetic associations of complex social traits","volume":"6","author":"TT Morris","year":"2020","journal-title":"Sci Adv"},{"key":"pmed.1003452.ref017","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/1471-2288-12-143","article-title":"The HUNT study: participation is associated with survival and depends on socioeconomic status, diseases and symptoms","volume":"12","author":"A Langhammer","year":"2012","journal-title":"BMC Med Res Methodol"},{"issue":"1","key":"pmed.1003452.ref018","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1093\/aje\/kwn096","article-title":"Body mass index in adolescence in relation to cause-specific mortality: a follow-up of 230,000 Norwegian adolescents","volume":"168","author":"T Bjorge","year":"2008","journal-title":"Am J Epidemiol"},{"issue":"4","key":"pmed.1003452.ref019","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1093\/ije\/dys095","article-title":"Cohort Profile: the HUNT Study, Norway","volume":"42","author":"S Krokstad","year":"2013","journal-title":"Int J Epidemiol"},{"key":"pmed.1003452.ref020","unstructured":"World Health Organization. Obesity and overweight [Internet]. 2020. http:\/\/www.who.int\/en\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"issue":"2","key":"pmed.1003452.ref021","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/oxfordjournals.aje.a009430","article-title":"Does body mass index adequately capture the relation of body composition and body size to health outcomes?","volume":"147","author":"KB Michels","year":"1998","journal-title":"Am J Epidemiol"},{"key":"pmed.1003452.ref022","unstructured":"Roser M, Appel C, Ritchie H. Human Height. May 2019 [2019 Sep 3]. [Internet]. 2013. https:\/\/ourworldindata.org\/human-height."},{"key":"pmed.1003452.ref023","unstructured":"Hunt Research Center. HUNT Databank [Internet]. 2020. https:\/\/hunt-db.medisin.ntnu.no\/hunt-db\/#\/."},{"issue":"9","key":"pmed.1003452.ref024","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1038\/s41588-018-0171-3","article-title":"Biobank-driven genomic discovery yields new insight into atrial fibrillation biology","volume":"50","author":"JB Nielsen","year":"2018","journal-title":"Nat Genet"},{"issue":"7571","key":"pmed.1003452.ref025","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"A Auton","year":"2015","journal-title":"Nature"},{"issue":"10026","key":"pmed.1003452.ref026","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/S0140-6736(16)00588-2","article-title":"A fatter, healthier but more unequal world","volume":"387","author":"GD Smith","year":"2016","journal-title":"Lancet"},{"key":"pmed.1003452.ref027","article-title":"Genetic predictors of participation in optional components of UK Biobank","author":"J Tyrrell","year":"2020","journal-title":"bioRxiv"},{"key":"pmed.1003452.ref028","unstructured":"Monsrud J. The car became ubiquited in 1960 [Internet]. 1999. https:\/\/www.ssb.no\/transport-og-reiseliv\/artikler-og-publikasjoner\/bilen-ble-allemannseie-i-1960."},{"key":"pmed.1003452.ref029","unstructured":"Consumed amounts of food and beverages per person per year, by commodity group. 1958\u20131998 [Internet]. Statistics Norway. https:\/\/www.ssb.no\/a\/histstat\/aarbok\/ht-0502-222.html."},{"key":"pmed.1003452.ref030","doi-asserted-by":"crossref","first-page":"k3147","DOI":"10.1136\/bmj.k3147","article-title":"Association between population mean and distribution of deviance in demographic surveys from 65 countries: cross sectional study","volume":"362","author":"F Razak","year":"2018","journal-title":"BMJ"},{"key":"pmed.1003452.ref031","first-page":"1","article-title":"The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins","author":"K Silventoinen","year":"2019","journal-title":"Twin Res Human Genet"},{"issue":"2","key":"pmed.1003452.ref032","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3945\/ajcn.117.153643","article-title":"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","volume":"106","author":"K Silventoinen","year":"2017","journal-title":"Am J Clin Nutr"},{"issue":"6","key":"pmed.1003452.ref033","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.ajhg.2017.10.007","article-title":"Penetrance of Polygenic Obesity Susceptibility Loci across the Body Mass Index Distribution","volume":"101","author":"A Abadi","year":"2017","journal-title":"Am J Hum Genet"},{"issue":"6460","key":"pmed.1003452.ref034","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.aax3710","article-title":"Deconstructing the sources of genotype-phenotype associations in humans","volume":"365","author":"AI Young","year":"2019","journal-title":"Science"},{"key":"pmed.1003452.ref035","unstructured":"Adult obesity facts [Internet]. 2018. https:\/\/www.cdc.gov\/obesity\/data\/adult.html."},{"issue":"3","key":"pmed.1003452.ref036","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1001\/jamapediatrics.2016.4136","article-title":"Processed food-an experiment that failed","volume":"171","author":"RH Lustig","year":"2017","journal-title":"JAMA Pediatr"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T18:24:43Z","timestamp":1607970283000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003452"}},"subtitle":[],"editor":[{"given":"Ronald C. W.","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,12,14]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1003452","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,14]]}}}