TY - JOUR
T1 - Combined Utility of 25 Disease and Risk Factor Polygenic Risk Scores for Stratifying Risk of All-Cause Mortality
AU - Meisner, Allison
AU - Kundu, Prosenjit
AU - Zhang, Yan Dora
AU - Lan, Lauren V.
AU - Kim, Sungwon
AU - Ghandwani, Disha
AU - Pal Choudhury, Parichoy
AU - Berndt, Sonja I.
AU - Freedman, Neal D.
AU - Garcia-Closas, Montserrat
AU - Chatterjee, Nilanjan
N1 - Funding Information:
This research has been conducted using the UK Biobank Resource under Application Number 17712. This research was supported by the Patient-Centered Outcomes Research Institute ( ME-1602-34530 ), the National Institutes of Health ( 1 R01 HG010480-01 ), and the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health .
Publisher Copyright:
© 2020 American Society of Human Genetics
PY - 2020/9/3
Y1 - 2020/9/3
N2 - While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data within the UK Biobank: the estimated hazard ratios per standard deviation were 1.10 (95% confidence interval: 1.05, 1.16) and 1.15 (1.10, 1.19) for women and men, respectively. Differences in life expectancy between the top and bottom 5% of the cPRS were estimated to be 4.79 (1.76, 7.81) years and 6.75 (4.16, 9.35) years for women and men, respectively. These associations were substantially attenuated after adjusting for non-genetic mortality risk factors measured at study entry (i.e., middle age for most participants). The cPRS may be useful in counseling younger individuals at higher genetic risk of mortality on modification of non-genetic factors.
AB - While genome-wide association studies have identified susceptibility variants for numerous traits, their combined utility for predicting broad measures of health, such as mortality, remains poorly understood. We used data from the UK Biobank to combine polygenic risk scores (PRS) for 13 diseases and 12 mortality risk factors into sex-specific composite PRS (cPRS). These cPRS were moderately associated with all-cause mortality in independent data within the UK Biobank: the estimated hazard ratios per standard deviation were 1.10 (95% confidence interval: 1.05, 1.16) and 1.15 (1.10, 1.19) for women and men, respectively. Differences in life expectancy between the top and bottom 5% of the cPRS were estimated to be 4.79 (1.76, 7.81) years and 6.75 (4.16, 9.35) years for women and men, respectively. These associations were substantially attenuated after adjusting for non-genetic mortality risk factors measured at study entry (i.e., middle age for most participants). The cPRS may be useful in counseling younger individuals at higher genetic risk of mortality on modification of non-genetic factors.
KW - all-cause mortality
KW - cause-specific mortality
KW - genetic risk stratification
KW - genome-wide association studies
KW - lifestyle modification
KW - polygenic risk scores
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U2 - 10.1016/j.ajhg.2020.07.002
DO - 10.1016/j.ajhg.2020.07.002
M3 - Article
C2 - 32758451
AN - SCOPUS:85089960637
SN - 0002-9297
VL - 107
SP - 418
EP - 431
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 3
ER -