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About the Authors:
Hakhamanesh Mostafavi
Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing - original draft
* E-mail: [email protected] (HM); [email protected] (MP); [email protected] (JKP)
Affiliation: Department of Biological Sciences, Columbia University, New York, New York, United States of America
ORCID http://orcid.org/0000-0002-1060-2844
Tomaz Berisa
Roles Conceptualization, Formal analysis, Investigation, Methodology, Writing - review & editing
Affiliation: New York Genome Center, New York, New York, United States of America
Felix R. Day
Roles Formal analysis, Investigation, Writing - review & editing
Affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
John R. B. Perry
Roles Formal analysis, Investigation, Writing - review & editing
Affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
Molly Przeworski
Contributed equally to this work with: Molly Przeworski, Joseph K. Pickrell
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing - original draft
* E-mail: [email protected] (HM); [email protected] (MP); [email protected] (JKP)
Affiliations Department of Biological Sciences, Columbia University, New York, New York, United States of America, Department of Systems Biology, Columbia University, New York, New York, United States of America
Joseph K. Pickrell
Contributed equally to this work with: Molly Przeworski, Joseph K. Pickrell
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing - original draft
* E-mail: [email protected] (HM); [email protected] (MP); [email protected] (JKP)
Affiliations Department of Biological Sciences, Columbia University, New York, New York, United States of America, New York Genome Center, New York, New York, United States of AmericaAbstract
A number of open questions in human evolutionary genetics would become tractable if we were able to directly measure evolutionary fitness. As a step towards this goal, we developed a method to examine whether individual genetic variants, or sets of genetic variants, currently influence viability. The approach consists in testing whether the frequency of an allele varies across ages, accounting for variation in ancestry. We applied it to the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and to the parents of participants in the UK Biobank. Across the genome, we found only a few common variants with large effects on age-specific mortality: tagging the APOE [epsilon]4 allele and near CHRNA3. These results suggest that when large, even late-onset effects are kept at low frequency by purifying...