For specific information about the dbGaP access, please contact:
Dr. Brinda Rana, O'Connor Twins Resource -- dbGaP
In all email inquiries, please put in subject line: O'Connor Twins dbGaP
https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs002230.v1.p1
Phenotypes
Phenotype data specifically focuses on the sympathetic branch of the autonomic system, which is a key regulator of blood pressure. Data includes circulating concentrations of the secretory “quantum” (catecholamines, neuropeptides, chromogranins) which influence vascular responses to sympatho-adrenal activation resulting in blood pressure. Other measures on the twins and a subset of family members include a standard urine panel with absolute concentrations of potassium, sodium, uric acid, phosphorous; DynaPulse acquired heart rate and blood pressure measures including systolic and diastolic blood pressure, mean arterial pressure, heart rate, Left Ventricular (LV) ejection time, LV contractility, cardiac output, stroke volume data including; and absolute concentrations of plasma aldosterone, endothelin, leptin, and insulin. Phenotype data is included for the 697 individuals sequenced here and 100 family members.
Whole Genome Sequence Data Generation
Whole genome sequencing (20X coverage) was conducted on plasma-derived DNA. The WGS was generated using the Illumina HiSeq X Ten sequencing platform with variants called by Human Longevity, Inc (HLI; Ref 1). Preparation of sample libraries was conducted by mechanical shearing of gDNA (100-800 bp), isolation of DNA fragments 300-500bp in size, followed by library PCR amplification employing high-fidelity, low-bias PCR to amplify library fragments consisting of appropriate adapter sequences on both ends. BAM files were created by alignment of sequence reads to the reference genome (GRCh38) using iSAAC-01.14.02.06 (Python2.7). Note: The user may want to realign the sequence data and recall variants.
In total, the WGS dataset contains 30 monozygotic twin pairs represented by one member of the twin pair, 133 monozygotic twin pairs with both individuals sequenced, 7 dizygotic twin pairs represented by one member of the twin pair, 67 dizygotic twin pairs with both individuals sequenced, 8 twin pairs with undetermined zygosity (both individuals sequenced) and 1 triplet with mother (all individuals sequenced). The dataset also contains sequences of 260 family members of twins including their mother, father, non-twin sibling, and offspring. Table 1 describes the composition of families (“sibling” refers to a non-twin sibling in the cohort). Note: We suggest users check gender and family relatedness.
Table 1: Description of the families with sequence data
Family Units |
||||
| Unit with: | Twin Pairs | Twin (no pair) | No twin | Sibships |
|---|---|---|---|---|
| Mother and Father | 5 | 1 | 1 | |
| Mother only | 12 | 2 | 2 | |
| Father only | 1 | 1 | 3 | |
| One or more siblings | 22 | 1 | 33 | |
| Mother and sibling | 1 | 3 | 2 | |
| Father and sibling(s) | 2 | 1 | 1 | |
| Offspring of twins | 1 | 1 | ||
| Other family member | 1 | 1 | ||
| Non-twin siblings | 2 | |||
| Sib with unknown relative | 1 | |||
| Only one member of | 8 | |||
References
1. Telenti A, Pierce LC, Biggs WH, di Iulio J, Wong EH, Fabani MM, Kirkness EF, Moustafa A, Shah N, Xie C, Brewerton SC, Bulsara N, Garner C, Metzker G, Sandoval E, Perkins BA, Och FJ, Turpaz Y, Venter JC. Deep sequencing of 10,000 human genomes. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11901-11906. doi: 10.1073/pnas.1613365113. Epub 2016 Oct 4. PMID: 27702888.