Whole Genome Linkage and Association Analyses Identify DLG Associated Protein-1 as a Novel Positional and Biological Candidate Gene for Muscle Strength: The Long Life Family Study

Abstract Background Grip strength is a robust indicator of overall health, is moderately heritable, and predicts longevity in older adults. Methods Using genome-wide linkage analysis, we identified a novel locus on chromosome 18p (mega-basepair region: 3.4–4.0) linked to grip strength in 3 755 individuals from 582 families aged 64 ± 12 years (range 30–110 years; 55% women). There were 26 families that contributed to the linkage peak (cumulative logarithm of the odds [LOD] score = 10.94), with 6 families (119 individuals) accounting for most of the linkage signal (LOD = 6.4). In these 6 families, using whole genome sequencing data, we performed association analyses between the 7 312 single nucleotide (SNVs) and insertion deletion (INDELs) variants in the linkage region and grip strength. Models were adjusted for age, age2, sex, height, field center, and population substructure. Results We found significant associations between genetic variants (8 SNVs and 4 INDELs, p