To understand the genetic basis of complex traits, it is important to be able to efficiently
phenotype many genetically distinct individuals. In the nematode Caenorhabditis elegans, individuals have
been isolated from diverse populations around the globe and whole-genome sequenced. As a result,
hundreds of wild strains with known genome sequences can be used for genome-wide association studies
(GWAS). However, phenotypic analysis of these strains can be laborious, particularly for quantitative traits
requiring multiple measurements per strain. Starvation resistance is likely a fitness-proximal trait for nematodes, and it is related to metabolic disease risk in humans. However, natural variation in C. elegans
starvation resistance has not been systematically characterized, and precise measurement of the trait is
time-intensive. Here, we developed a population-selection-and-sequencing-based approach to phenotype
starvation resistance in a pool of 96 wild strains. We used restriction site-associated DNA sequencing
(RAD-seq) to infer the frequency of each strain among survivors in a mixed culture over time during
starvation. We used manual starvation survival assays to validate the trait data, confirming that strains that
increased in frequency over time are starvation-resistant relative to strains that decreased in frequency.
Further, we found that variation in starvation resistance is significantly associated with variation at a region
on chromosome III. Using a near-isogenic line (NIL), we showed the importance of this genomic interval for
starvation resistance. This study demonstrates the feasibility of using population selection and sequencing
in an animal model for phenotypic analysis of quantitative traits, documents natural variation of starvation
resistance in C. elegans, and identifies a genomic region that contributes to such variation