Pulse lineResearch With Heart Logo

Structural Brain MRI Trait Polygenic Score Prediction of Cognitive Abilities.

TitleStructural Brain MRI Trait Polygenic Score Prediction of Cognitive Abilities.
Publication TypeJournal Article
Year of Publication2015
AuthorsLuciano M, Marioni RE, Hernández MValdés, Maniega SMuñoz, Hamilton IF, Royle NA, Chauhan G, Bis JC, Debette S, DeCarli C, Fornage M, Schmidt R, M Ikram A, Launer LJ, Seshadri S, Bastin ME, Porteous DJ, Wardlaw J
Secondary AuthorsDeary IJ
Corporate AuthorsGeneration Scotland, CHARGE Consortium
JournalTwin Res Hum Genet
Volume18
Issue6
Pagination738-45
Date Published2015 Dec
ISSN1832-4274
KeywordsBrain, Cognition, Female, Forecasting, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Multifactorial Inheritance, Neuropsychological Tests
Abstract

Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115-8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.

DOI10.1017/thg.2015.71
Alternate JournalTwin Res Hum Genet
PubMed ID26427786
PubMed Central IDPMC4747328
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
AG 033193 / AG / NIA NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01AG15928 / AG / NIA NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
R01 AG015928 / AG / NIA NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
R01 HL068986 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
NS087541 / NS / NINDS NIH HHS / United States
HL096917 / HL / NHLBI NIH HHS / United States
R01 NS17950 / NS / NINDS NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
AG033193 / AG / NIA NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
G1001245 / / Medical Research Council / United Kingdom
U01 HG004402 / HG / NHGRI NIH HHS / United States
HL093029 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
MR/K026992/1 / / Medical Research Council / United Kingdom
HL120393 / HL / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
HL068986 / HL / NHLBI NIH HHS / United States
R01-HL087641 / HL / NHLBI NIH HHS / United States
R01 HL093029 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
CZD/16/6/4 / / Chief Scientist Office / United Kingdom
N01HC55016 / HL / NHLBI NIH HHS / United States
R01AG20098 / AG / NIA NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
G0700704 / / Medical Research Council / United Kingdom
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
BB/F019394/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
N01HC85079 / HL / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
HL103612 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
AG008122 / AG / NIA NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States