Abstract
Human DNA polymorphisms vary across geographic regions, with the most commonly observed variation reflecting distant ancestry differences. Here we investigate the geographic clustering of common genetic variants that influence complex traits in a sample of ~450,000 individuals from Great Britain. Of 33 traits analysed, 21 showed significant geographic clustering at the genetic level after controlling for ancestry, probably reflecting migration driven by socioeconomic status (SES). Alleles associated with educational attainment (EA) showed the most clustering, with EA-decreasing alleles clustering in lower SES areas such as coal mining areas. Individuals who leave coal mining areas carry more EA-increasing alleles on average than those in the rest of Great Britain. The level of geographic clustering is correlated with genetic associations between complex traits and regional measures of SES, health and cultural outcomes. Our results are consistent with the hypothesis that social stratification leaves visible marks in geographic arrangements of common allele frequencies and gene-environment correlations.
| Original language | English |
|---|---|
| Pages (from-to) | 1332-1342 |
| Number of pages | 11 |
| Journal | Nature Human Behaviour |
| Volume | 3 |
| Issue number | 12 |
| Early online date | 21 Oct 2019 |
| DOIs | |
| Publication status | Published - Dec 2019 |
Funding
The participants of this study come from UK Biobank (UKB), which has received ethical approval from the National Health Service North West Centre for Research Ethics Committee (reference: 11/NW/0382). This research was supported by the Australian National Health and Medical Research Council (1107258, 1078901, 1078037, 1056929, 1048853 and 1113400) and the Sylvia and Charles Viertel Charitable Foundation (Senior Medical Research Fellowship). A.A. and K.J.H.V. are supported by the Foundation Volksbond Rotterdam. A.A. and M.G.N. are supported by ZonMw grants 849200011 and 531003014 from The Netherlands Organisation for Health Research and Development. B.P.Z. received funding from the Australian Research Council (FT160100298). The research was conducted using data from the UK Biobank Resource (application number: 12514) and dbGaP (accession number: phs000674). The Genetic Epidemiology Research on Adult Health and Aging study was supported by grant RC2 AG036607 from the National Institutes of Health, as well as grants from the Robert Wood Johnson Foundation, Ellison Medical Foundation, Wayne and Gladys Valley Foundation and Kaiser Permanente. The authors thank the Kaiser Permanente Medical Care Plan, Northern California Region members who participated in the Kaiser Permanente Research Program on Genes, Environment and Health. This study was conducted using UK Biobank resources under application number 12514. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and Northwest Regional Development Agency. It also received funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
| Funders | Funder number |
|---|---|
| Foundation Volksbond Rotterdam | |
| Medical Research Council, Department of Health | |
| National Health Service North West Centre for Research Ethics Committee | 11/NW/0382 |
| Welsh Assembly Government | |
| National Institutes of Health | |
| National Institute on Aging | RC2AG036607 |
| Ellison Medical Foundation | |
| Robert Wood Johnson Foundation | |
| Valley Foundation | |
| Kaiser Permanente | |
| Sylvia and Charles Viertel Charitable Foundation | |
| Wellcome Trust | |
| British Heart Foundation | |
| Diabetes UK | |
| Australian Research Council | RC2 AG036607, FT160100298 |
| National Health and Medical Research Council | 1078901, 1048853, 1107258, 1113400, 1056929, 1078037 |
| ZonMw | 531003014, 849200011 |
| Northwest Regional Development Agency |
