ABSTRACT
The field of genomics has entered a new era in which the ability to identify genetic
variants that impact complex human traits and disease in an unbiased fashion using
genome-wide approaches is widely accessible. To date, the workhorse of these efforts
has been the genome-wide association study (GWAS), which has quickly moved from novel
to routine, and has provided key insights into aspects of the underlying allelic architecture
of complex traits. The main lesson learned from the early GWAS efforts is that though
many disease-associated variants are often discovered, most have only a minor effect
on disease, and in total explain only a small amount of the apparent heritability.
Here we provide a brief overview of the genetic variation classes that may harbor
the heritability missing from GWAS, and touch on approaches that will be leveraged
in the coming years as genomics—and by extension medicine—becomes increasingly personalized.
KEYWORDS
Genetics - genomics - GWAS - liver - complex disease
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Konstantinos N LazaridisM.D.
Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine
200 First Street SW, Rochester, MN 55905
Email: lazaridis.konstantinos@mayo.edu
