Biodemographic Specifics of the Effects of Body-Mass-Index Risk Alleles Identified in Genome-Wide Association Studies

Alexander Kulminski, Duke University
Irina V. Culminskaya, Duke University
Konstantin G. Arbeev, Duke University
Liubov Arbeeva, Duke University
Svetlana V. Ukraintseva, Duke University
Eric Stallard, Duke University
Deqing Wu, Duke University
Kaare Christensen, University of Southern Denmark and Odense University Hospital
Michael Province, Washington University in St. Louis
Ingrid Borecki, Washington University in St. Louis
Ryan Minster, University of Pittsburgh
Anatoliy I. Yashin, Duke University

Genome-wide association studies (GWAS) have been thought as breakthrough in gaining insights into genetic origin of healthspan and mortality. The optimism is, however, tempered because GWAS face serious difficulties. It is believed that these difficulties can be overcome using the large sample sizes achievable through collaboration. Implicitly, such strategy relies on existence of unconditional genetic risks that is, generally, questionable. As a consequence, GWAS ignores possible complexity of genetic effects across the life course that results in non-informativeness of increasing samples. We re-examined in detail the associations of SNPs which were identified as correlates of BMI in a recent Nature meta-analysis using cohorts from different generations participated in the Framingham Heart Study and the Long Life Family Study. Our preliminary results suggest that simplistic strategies on increasing sample sizes in GWAS are at least not efficient. The results suggest that gaining insights into bio-demographic specifics of the studied populations may be crucial.

  See extended abstract

Presented in Session 21: Genetic Risk and Family, Environment and the Life Course