DOI: 10.60645/bdc-y42d-8983
title: NHLBI Framingham SNP Health Association Resource (SHARe)

description: 
This substudy phs000342 Framingham SHARe contains a large number of historical and contemporary FHS genotypes. These include 100K, 550K, HumanOmni5M-4v1, HumanExome BeadChip v1.0, Affymetrix Axiom Genome-Wide BioBank, and Illumina Global Screening array sets; three different imputed data sets; focused genotype sets including apoE, genotypes of rare type 2 diabetes (T2D) associated risk variants, and legacy genotypes.

Summary level phenotypes for the Framingham Cohort study participants can be viewed at the top-level study page [phs000007](./study.cgi?study_id=phs000007) Framingham Cohort. Individual level phenotype data and molecular data for all Framingham top-level study and substudies are available by requesting Authorized Access to the Framingham Cohort study [phs000007](./study.cgi?study_id=phs000007). Descriptions of the various genotype resources are summarized below.


**100K Genome-Wide Association Study and Results Browser**. A subset of 1345 adult participants (original cohort and offspring) of the largest 310 pedigrees in the FHS, many biologically related, was genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to a wide range of traits collected in FHS over 59 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. Genome-wide variance component linkage and population and family-based association tests were conducted. An overview manuscript, as well as 17 manuscripts describing the unreplicated results of analyses of the various phenotypes, was published in a supplement of BMC Medical Genetics in September 2007. A link to the full disclosure results of these analyses is available through dbGaP on the Analyses page.


**Framingham Heart Study SHARe 550K Genome-Wide Association Study**. In 2007, the FHS entered a new phase with the conduct of genotyping for the FHS SHARe project, for which genotyping was conducted using approximately 550,000 SNPs (Affymetrix 500K mapping array plus Affymetrix 50K supplemental array) in over 9,300 participants from the three generations of participants (including over 1500 families). The SHARe database is housed at NCBI's dbGaP and contains all 550,000 SNPs as well as SNP and microsatellite genotyping conducted previously in the FHS.


**Illumina HumanOmni5M-4v1 Array**. In 2011, genotyping of approximately 4.3 million SNPs was conducted in subset of 2500 Framingham Offspring Cohort participants using the Illumina HumanOmni5M-4v1 array designed to target variation down to 1% minor allele frequency. This genotyping was produced at no charge by Illumina under an agreement between Illumina and Boston University.


**HumanExome BeadChip v1.0**. 8153 participant samples from the three generations of participants were processed on the HumanExome BeadChip v1.0 (Illumina, Inc., San Diego, CA) that contains putative functional exonic variants selected from individual exome and whole-genome sequences from diverse populations. It includes nonsynonymous variants, splice variants and stop-altering variants. It also includes tags for previous GWAS-identified loci, ancestry informative markers, markers designed for identity by descent analyses, synonymous variants, fingerprint SNPs common to major genotyping platforms, mitochondrial SNPs, chromosome Y SNPs, and HLA tag SNPs. A detailed description of the variant calling and QC can be found in https://doi.org/10.1371/journal.pone.0068095 


**Affymetrix Axiom Genome-Wide BioBank genotyping Array**. In 2014, genotyping of approximately 628,000 SNPs was conducted in subset of 860 Framingham Omni 1 and Omni 2 Cohort participants using the Affymetrix Axiom Genome-Wide BioBank array designed to target variation down to 1% minor allele frequency in diverse populations. Additionally, the array contains standard design content including coding SNPs and indels, loss-of-function SNPs and indels based on exome sequencing projects, expression QTL markers, and pharmacogenomics markers. This genotyping was produced via NHLBI Intramural funding primarily to Andrew D. Johnson and secondarily to Christopher J. O&#39;Donnell.


**Illumina Global Screening array**. These data were generated as part of the Alzheimer&#39;s Disease (AD) Sequencing Project (ADPS), which aims to identify novel risk and protective genetic variants for AD with the ultimate goal of identifying novel drug targets for the disease. To maximize power and gain insight into biological function, they  gathered a large  and diverse sample of community-based individuals of African, Hispanic, Asian, and European ancestry, extensively characterized for AD and related endophenotypes. As part of this sample, DNA was extracted from brain tissue of n=13 participants who were part of the Framingham brain donation program and for whom genotyping was not available. Genotyping was performed using the Illumina Global Screening Array (GSA) chip.


**Imputed data sets**. Imputation was performed on 8481 participants with quality SHARe GWAS data. A total of three imputation panels are available including: HapMap phaseII, 1,000&#8233;Genomes, and the Human Reference Consortium (HRC1).


**apoE genotype**. Human APOE gene is polymorphic at two single nucleotides (rs429358 and rs7412) resulting in three different alleles (&#949;2, &#949;3 and &#949;4). Direct genotyping of APOE in whole blood samples from 10455 participants was performed in three batches; the original cohort, offspring cohort, and all remaining cohorts (NOS, OMNI1, OMNI2).


**T2D related genotypes**. In 2014 genotypes of rare variants in genomic regions associated with risk of type 2 diabetes (T2D) or diabetes related quantitative traits that are not part of extant genotyped or imputed GWAS data in Framingham Heart Study cohorts were added to this substudy. This genotyping was produced using a TaqMan ABI PRISM 7700 HT Sequence Detection System (Applied Biosystems, Foster City, CA) at the Joslin Diabetes Center Genetics and Epidemiology Research Core under the R01 DK078616 (to J.B. Meigs) NIH Grant.


**Legacy genotypes**. Contains a bolus of historical microsatellite and SNP genotypes primarily from original and offspring cohorts. apoE genotypes included *should not be utilized* as they are limited to original and offspring cohort genotypes only.