Novel Positional Candidate Gene for Gait Speed Change in Older Adults: The Long Life Family Study

Gait speed is a heritable, robust predictor of longevity in older adults. Using genome-wide linkage analysis in 2379 individuals from 509 families (64±12 years; 45% men), we identified a locus on chromosome 16p linked to gait speed change over 7±1 years (logarithm of the odds score [LOD]=4.2). Gait speed change was calculated using a two-stage growth curve mixed-model. DNA sequencing was completed to identify single nucleotide variants (SNVs) in the linkage region. Association analyses between the 24039 SNVs in the ~1.6mBP region (3.7-5.3mBP) and gait speed change were performed adjusting for age, age2, sex, height, field center, familial relatedness and population substructure. Eleven families (188 individuals) accounted for most of the linkage signal (LOD=6.06). Associations between SNVs flanking the Mesothelin (MSLN) gene and gait speed change were identified (lead SNV rs56850119: β = -0.5±0.1, p = 6.4*10-7). Thus, MSLN is a potential positional candidate gene for mobility decline with aging.

Genome-wide association study for backfat thickness at 100 kg and loin muscle thickness in domestic pigs based on genotyping by sequencing

Both backfat thickness at 100 kg (B100) and loin muscle thickness (LMT) are economically important traits in pigs. In this study, a total of 1,200 pigs (600 Landrace and 600 Yorkshire pigs) were examined with genotyping by sequencing. A total of 345,570 single nucleotide polymorphisms (SNPs) were obtained from 1,200 pigs. Then, a single marker regression test was used to conduct a genome-wide association study for B100 and LMT. A total of 8 and 90 significant SNPs were detected for LMT and B100, respectively. Interestingly, two shared significant loci [located at Sus scrofa chromosome (SSC) 6: 149876694 and SSC12: 46226580] were detected in two breeds for B100. Furthermore, three potential candidate genes were found for LMT and B100. The positional candidate gene FAM3C (SSC18: 25573656, P = 2.48 × 10−9), which controls the survival, growth, and differentiation of tissues and cells, was found for LMT in Landrace pigs. At SSC9: 6.78–6.82 Mb in Landrace pigs, the positional candidate gene, INPPL1, which has a negative regulatory effect on diet-induced obesity and is involved in the regulation of insulin function, was found for B100. The candidate gene, RAB35, which regulates the adipocyte glucose transporter SLC2A4/ GLUT4, was identified at approximately SSC14: 40.09–40.13 Mb in Yorkshire pigs. The results of this GWAS will greatly advance our understanding of the genetic architecture of the LMT and B100 traits. However, these identified loci and genes need to be further verified in more pig populations, and their functions also need to be validated by more biological experiments in pigs.