Dataset Information

A Prospective Analysis of Genetic Variants Associated with Human Lifespan.

ABSTRACT: We present a massive investigation into the genetic basis of human lifespan. Beginning with a genome-wide association (GWA) study using a de-identified snapshot of the unique AncestryDNA database - more than 300,000 genotyped individuals linked to pedigrees of over 400,000,000 people - we mapped six genome-wide significant loci associated with parental lifespan. We compared these results to a GWA analysis of the traditional lifespan proxy trait, age, and found only one locus, APOE, to be associated with both age and lifespan. By combining the AncestryDNA results with those of an independent UK Biobank dataset, we conducted a meta-analysis of more than 650,000 individuals and identified fifteen parental lifespan-associated loci. Beyond just those significant loci, our genome-wide set of polymorphisms accounts for up to 8% of the variance in human lifespan; this value represents a large fraction of the heritability estimated from phenotypic correlations between relatives.

SUBMITTER: Wright KM

PROVIDER: S-EPMC6723124 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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A Prospective Analysis of Genetic Variants Associated with Human Lifespan.

Wright Kevin M KM Rand Kristin A KA Kermany Amir A Noto Keith K Curtis Don D Garrigan Daniel D Slinkov Dmitri D Dorfman Ilya I Granka Julie M JM Byrnes Jake J Myres Natalie N Ball Catherine A CA Ruby J Graham JG

G3 (Bethesda, Md.) 20190904 9

We present a massive investigation into the genetic basis of human lifespan. Beginning with a genome-wide association (GWA) study using a de-identified snapshot of the unique <i>AncestryDNA</i> database - more than 300,000 genotyped individuals linked to pedigrees of over 400,000,000 people - we mapped six genome-wide significant loci associated with parental lifespan. We compared these results to a GWA analysis of the traditional lifespan proxy trait, age, and found only one locus, <i>APOE</i>, ...[more]

PMID: 31484785

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Project description:BackgroundIn the past decade, accumulated evidence has suggested that genetic variation is related to the pathogenesis of osteosarcoma. Although there are a large number of studies on the association between genetic variation and osteosarcoma, their results are inconsistent. To clarify these findings, we performed a systematic meta-analysis using allelic contrasts for each gene-specific single nucleotide variants with all available data in the field of osteosarcoma.MethodsThe literature search for relevant studies was conducted in PubMed, Embase, and Cochrane databases. Pooled ORs and 95% CI values were calculated by the random-effects model using the Comprehensive Meta-analysis version 2.0 software package. Heterogeneity between studies was examined by the Cochran's Q-test.ResultsThe 32 genome-wide case-control population-based studies, involving 15,336 study subjects (6924 cases and 8412 controls), were included in this meta-analysis. We analyzed 24 single nucleotide variants (SNVs) in 14 genes. We identified 12 SNVs in CTLA-4, IL-8, MDM2, PRCKG, RECQL5, TNF-a, TP53, XRCC3, and VEGF that correlated with osteosarcoma susceptibility. The average pooled odds ratio for the 9 risk alleles was 2.082 (range: 1.585 to 3.262). These included CTLA-4 rs231775, CTLA-4 rs5742909, PRCKG rs454006, RECQL5 rs820196, TNF-α rs1800629, TP53 rs1042522, XRCC3 rs861539, VEGF rs699947, and VEGF rs3025039. The average pooled odds ratio for the 3 protective alleles, IL-8 rs4073, MDM2 rs1690916, and VEGF rs2010963, was 0.606 (range: 0.510-0.719). Publication bias was not observed among the studies reporting positively correlated SNVs. The pooled odds ratios for the SNVs that correlated with osteosarcoma risk showed homogeneity.ConclusionOur results provide powerful information for tracking the most viable gene candidates. Further studies with larger multiethnicity populations and investigations of the potential biological roles of these genetic variants in osteosarcoma should be conducted.

Dataset Information

A Prospective Analysis of Genetic Variants Associated with Human Lifespan.

Publications

A Prospective Analysis of Genetic Variants Associated with Human Lifespan.

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