1. Tensin 1 (TNS1) is a modifier gene for low body mass index (BMI) in homozygous [F508del]CFTR patients
- Author
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Nathan I. Walton, Clifton L. Dalgard, Harvey B. Pollard, Douglas Conrad, Xijun Zhang, Matthew D. Wilkerson, Joshua Starr, and Anthony R. Soltis
- Subjects
Adult ,Male ,Heterozygote ,Cystic Fibrosis ,Physiology ,Cystic Fibrosis Transmembrane Conductance Regulator ,Single-nucleotide polymorphism ,030204 cardiovascular system & hematology ,Biology ,Compound heterozygosity ,Cystic fibrosis ,Polymorphism, Single Nucleotide ,Body Mass Index ,03 medical and health sciences ,BMI ,0302 clinical medicine ,Thinness ,Physiology (medical) ,Tensins ,medicine ,QP1-981 ,Tensin ,Humans ,Gene ,Whole genome sequencing ,Genetics ,whole genome sequencing ,Homozygote ,Chromosome ,Original Articles ,medicine.disease ,TNS1 ,Original Article ,Female ,Gastrointestinal function ,030217 neurology & neurosurgery - Abstract
Cystic fibrosis (CF) is a life‐limiting autosomal recessive genetic disease caused by variants in the CFTR gene, most commonly by the [F508del] variant. Although CF is a classical Mendelian disease, genetic variants in several modifier genes have been associated with variation of the clinical phenotype for pulmonary and gastrointestinal function and urogenital development. We hypothesized that whole genome sequencing of a well‐phenotyped CF populations might identify novel variants in known, or hitherto unknown, modifier genes. Whole genome sequencing was performed on the Illumina HiSeq X platform for 98 clinically diagnosed cystic fibrosis patient samples from the Adult CF Clinic at the University of California San Diego (UCSD). We compared protein‐coding, non‐silent variants genome wide between CFTR [F508del] homozygotes vs CFTR compound heterozygotes. Based on a single variant score test, we found 3 SNPs in common variants (MAF >5%) that occurred at significantly different rates between homozygous [F508del]CFTR and compound heterozygous [F508del]CFTR patients. The 3 SNPs were all located in one gene on chromosome 2: Tensin 1 (TNS1: rs3796028; rs2571445: and rs918949). We observed significantly lower BMIs in homozygous [F508del]CFTR patients who were also homozygous for Tensin 1 rs918949 (T/T) (p = 0.023) or rs2571445 (G/G) (p = 0.02) variants. The Tensin 1 gene is thus a potential modifier gene for low BMI in CF patients homozygous for the [F508del]CFTR variant., We hypothesized that whole genome sequencing of a well‐phenotyped CF populations might identify novel variants in known, or hitherto unknown, modifier genes. We compared protein‐coding, non‐silent variants genomewide between CFTR [F508del] homozygotes vs CFTR compound heterozygotes. We found that the Tensin 1 gene is a potential modifier gene for low BMI in CF patients homozygous for the [F508del]CFTR variant.
- Published
- 2021