SardiNIA Medical Sequencing Discovery Project

The SardiNIA Medical Sequencing Discovery Project studies the genetics of blood lipid levels and personality in a Sardinian population cohort. The project has generated draft genome sequences for approximately 2,000 individuals using whole genome shotgun sequencing. The draft sequences will allow investigators to evaluate the contribution of common and rare single nucleotide polymorphisms, short insertions and deletions, large copy number polymorphisms and other structural variants to blood levels of low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TG), all of which are key risk factors for cardiovascular disease, and to the 5 domains of personality as assessed by the NEO-PI-R questionnaire. The two traits represent different ends of the spectrum of medically interesting complex traits. Blood lipid levels are a risk factor for cardiovascular disease for which genetic studies have been very successful. In contrast, personality traits and other behavioral phenotypes represent a set of phenotypes that have proven more challenging to dissect using standard genetic tools. In both cases, we expect whole genome sequencing to improve our understanding of the underlying biology. The isolated Sardinian population is ideal for this type of study for several reasons, in particular because: (i) the bottleneck that occurred after colonization of the island attenuated natural selection against alleles with phenotypic consequences, increasing the odds that functional alleles will reach modest frequencies (0.5 - 5.0%) and will be detected in the present study and (ii) sharing of long haplotype stretches surrounding rare variants will facilitate imputation based analyses of shotgun sequence data, which improve the accuracy of individual genotype calls and thus increase power. This research helps advance NIH's mission by furthering our understanding of the genetic factors contributing to blood lipid levels and coronary heart disease and to personality, behavior and mental health. In addition, these data should facilitate development of analysis tools and strategies that can be used to study the genomes of hundreds to thousands of individuals and further our understanding of the genetics and biology of many different traits and conditions.]]>
All individuals selected for sequencing were 21 years and older. Two individuals who had received bone marrow transplants were excluded from sequencing. The current data set contains information on 2077 sequenced and 2105 phenotyped individuals. Sequence data have been updated in May 2015 with additional individuals, additional coverage and uniform read mapping to the 1000 Genomes hs37d5 decoy reference.]]>
Phenotypic Assessments: 2001-2004: Initial Participant Recruitment 2005-2007: 2nd Evaluation of Study Participants 2008-2010: 3rd Evaluation of Study Participants 2011-present: 4th Evaluation of Study Participants Genotypic Assessments: 2005-2006: Initial round of Genomewide Genotyping, Affymetrix 10K and 500K arrays 2009-2011: Initial round of Genomewide Sequencing 2011-2013: Genomewide genotyping using Illumina Metabochip, Immunochip, ExomeChip and Human Omni Express genotyping arrays. 2015: Sequence data updated with additional individuals, additional coverage and uniform read mapping to the 1000 Genomes hs37d5 decoy reference. Key Publications: 2006: Summary of Phenotypic Assessments Published (Pilia et al, 2006) 2007: First Genomewide Association Study Results (Scuteri et al, 2007) 2008: First Genomewide Association Meta-Analyses (Sanna et al, 2008, Willer et al, 2008) 2009-2010: Continuing Genomewide Analyses 2013: First sequence-based genomewide analyses (Orrù et al, 2013) ]]>