Apparent latent structure within the UK Biobank sample has implications for epidemiological analysis.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
18 01 2019
18 01 2019
Historique:
received:
10
05
2018
accepted:
09
11
2018
entrez:
20
1
2019
pubmed:
20
1
2019
medline:
7
2
2019
Statut:
epublish
Résumé
Large studies use genotype data to discover genetic contributions to complex traits and infer relationships between those traits. Co-incident geographical variation in genotypes and health traits can bias these analyses. Here we show that single genetic variants and genetic scores composed of multiple variants are associated with birth location within UK Biobank and that geographic structure in genotype data cannot be accounted for using routine adjustment for study centre and principal components derived from genotype data. We find that major health outcomes appear geographically structured and that coincident structure in health outcomes and genotype data can yield biased associations. Understanding and accounting for this phenomenon will be important when making inference from genotype data in large studies.
Identifiants
pubmed: 30659178
doi: 10.1038/s41467-018-08219-1
pii: 10.1038/s41467-018-08219-1
pmc: PMC6338768
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
333Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00011/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 19169
Pays : United Kingdom
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/4
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12013/3
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Références
Science. 2018 Jan 26;359(6374):424-428
pubmed: 29371463
Nat Genet. 2012 Sep;44(9):1015-9
pubmed: 22902787
Am J Hum Genet. 2011 Jul 15;89(1):191-3; author reply 193-5
pubmed: 21763486
Lancet. 2003 Feb 15;361(9357):598-604
pubmed: 12598158
PLoS Genet. 2012 Jan;8(1):e1002453
pubmed: 22291602
Sci Rep. 2016 May 25;6:26471
pubmed: 27220488
Nat Genet. 2006 Aug;38(8):904-9
pubmed: 16862161
Int J Epidemiol. 2018 Feb 1;47(1):226-235
pubmed: 29040562
Psychiatr Genet. 2018 Oct;28(5):85-89
pubmed: 30160659
Nat Genet. 2014 Nov;46(11):1173-86
pubmed: 25282103
Elife. 2019 Mar 21;8:
pubmed: 30895923
Nat Rev Genet. 2005 Aug;6(8):623-32
pubmed: 16012528
Science. 2014 Feb 14;343(6172):747-751
pubmed: 24531965
Nature. 2015 Mar 19;519(7543):309-314
pubmed: 25788095
Genet Epidemiol. 2008 May;32(4):381-5
pubmed: 18348202
Nat Genet. 2012 Jul 22;44(8):955-9
pubmed: 22820512
Nat Genet. 2018 Mar;50(3):390-400
pubmed: 29403010
Elife. 2018 May 30;7:
pubmed: 29846171
PLoS One. 2011;6(12):e28845
pubmed: 22216125
Nat Genet. 2018 Sep;50(9):1304-1310
pubmed: 30104764
Gigascience. 2015 Feb 25;4:7
pubmed: 25722852
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E727-E732
pubmed: 28096410
Trends Genet. 2013 Feb;29(2):66-73
pubmed: 23140989
PLoS Genet. 2014 Aug 07;10(8):e1004412
pubmed: 25102153
Nat Commun. 2018 Aug 14;9(1):3258
pubmed: 30108219
Int J Epidemiol. 2013 Feb;42(1):111-27
pubmed: 22507743
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7377-82
pubmed: 27382152
Nat Genet. 2012 Feb 05;44(3):243-6
pubmed: 22306651
Int J Epidemiol. 2013 Feb;42(1):97-110
pubmed: 22507742
Int J Epidemiol. 2010 Apr;39(2):417-20
pubmed: 19926667
Schizophr Res. 2018 Jul;197:2-8
pubmed: 29129507
Hum Mol Genet. 2014 Sep 15;23(R1):R89-98
pubmed: 25064373
Stat Med. 2008 Apr 15;27(8):1133-63
pubmed: 17886233
RSF. 2018 Apr;4(4):137-149
pubmed: 30740524
Am J Epidemiol. 2017 Nov 1;186(9):1026-1034
pubmed: 28641372
Nature. 2016 May 11;533(7604):539-42
pubmed: 27225129
Nature. 2015 Dec 24;528(7583):499-503
pubmed: 26595274
Int J Epidemiol. 2018 Aug 1;47(4):1207-1216
pubmed: 29800128
Nat Genet. 2015 Nov;47(11):1357-62
pubmed: 26366552
Eur Heart J. 2016 Nov 14;37(43):3267-3278
pubmed: 27655226
Nat Methods. 2011 Dec 04;9(2):179-81
pubmed: 22138821
Lancet. 2012 Mar 31;379(9822):1173-4
pubmed: 22463865
Nature. 2015 Feb 12;518(7538):197-206
pubmed: 25673413