title: Burden of Common Complex Disease Variants in the Exomes of Two Healthy Centenarian Brothers.
abstract: BACKGROUND
  It is not understood whether long-term good health is promoted by the absence of disease risk variants, the presence of protective variants, or both. We characterized the exomes of two exceptionally healthy centenarian brothers aged 106 and 109 years who had never been diagnosed with cancer, cardiovascular disease, diabetes, Alzheimer's disease, or major pulmonary disease.
  
  
  OBJECTIVE
  The aim of this study was to gain insight into whether exceptional health and longevity are a result of carrying fewer disease-associated variants than typical individuals.
  
  
  METHODS
  We compared the number of disease-associated alleles, and the proportion of alleles predicted to be functionally damaging, between the centenarian brothers and published population data. Mitochondrial sequence reads were extracted from the exome data in order to analyze mitochondrial variants.
  
  
  RESULTS
  The brothers carry a similar number of common disease-associated variants and predicted damaging variants compared to reference groups. They did not carry any high-penetrance clinically actionable variants. They carry mitochondrial haplogroup T, and one brother has a single heteroplasmic variant.
  
  
  CONCLUSIONS
  Although our small sample size does not allow for definitive conclusions, a healthy aging and longevity phenotype is not necessarily due to a decreased burden of common disease-associated variants. Instead, it may be rare 'positive' variants that play a role in this desirable phenotype.
authors.affiliation: Department of Biomedical Physiology and Kinesiology, Simon Fraser University, Burnaby, B.C., Canada.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Tindale
authors.forename: Andy
authors.initials: A
authors.lastname: Zeng
authors.forename: Karla L
authors.initials: KL
authors.lastname: Bretherick
authors.forename: Stephen
authors.initials: S
authors.lastname: Leach
authors.forename: Nina
authors.initials: N
authors.lastname: Thiessen
authors.forename: Angela R
authors.initials: AR
authors.lastname: Brooks-Wilson
mesh_terms: D000369:Aged, 80 and over; D000375:Aging; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type; D004272:DNA, Mitochondrial / Q000235:genetics; D004194:Disease / Q000235:genetics*; D059472:Exome; D024522:Genes, BRCA2; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008136:Longevity; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: D001055:Apolipoproteins B; C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004272:DNA, Mitochondrial