Methods of predicting aneurysms of the ascending and descending aorta
The disclosure provides methods of assessing a subject's risk of ascending thoracic aortic aneurysm or descending thoracic aortic aneurysm by detecting one or more single nucleotide polymorphisms (SNP) in one or more specific genes. The disclosure also provides methods of calculating a polygenic score to assess a subjects risk. Such methods may be used, for example, to identify asymptomatic subjects at risk for aneurysm.
1 . A method for assessing a human subject's risk for an aneurysm of the ascending thoracic aorta, comprising:
detecting, in a sample from the human subject, a G allele at single nucleotide polymorphism (SNP) rs1441358 in;
determining that the human subject is at increased risk for the aneurysm of the ascending thoracic aorta based on the detection; and
administering to the human subject a treatment to reduce the risk for the aneurysm of the ascending thoracic aorta, the treatment comprising a medication, a surgery, or both.
2 . The method of claim 1 , further comprising:
detecting, in the sample, an allele at SNP rs9847006 in ULK4;
calculating a polygenic score based on the number of SNPs detected the G allele at the SNP rs1441358 in THSD4 and the detected allele at the SNP rs9847006 in ULK4, wherein detection of a T allele at the SNP rs9847006 in ULK4 increases the polygenic score; and
determining that the human subject is at a further increased risk for the aneurysm of the ascending thoracic aorta when the polygenic score is greater than a reference polygenic score calculated from a population of subjects who do not have thoracic aortic aneurysms.
3 . The method of claim 2 , further comprising administering thoracic imaging to the human subject when the polygenic score is greater than the reference polygenic score.
4 . The method of claim 1 , further comprising assessing an aortic diameter of the human subject relative to a mean reference aortic diameter.
5 . The method of claim 4 , wherein the aortic diameter is determined by computed tomography (CT), magnetic resonance imaging (MRI), or echocardiography.
6 . The method of claim 1 , wherein;
the medication is selected from the group consisting of: aspirin, blood pressure medications, and statins; and
the surgery is open surgical repair or endovascular aneurysm repair.
7 . The method of claim 1 , further comprising:
detecting, in the sample, an allele at SNP rs56298756 in USP15;
calculating a polygenic score based on the G allele at the SNP rs1441358 in THSD4 and the detected allele at the SNP rs56298756 in USP15, wherein detection of a T allele at the SNP rs56298756 in USP15 increases the polygenic score; and
determining that the human subject is at a further increased risk for the aneurysm of the ascending thoracic aorta when the polygenic score is greater than a reference polygenic score calculated from a population of subjects who do not have thoracic aortic aneurysms.
8 . The method of claim 7 , further comprising administering thoracic imaging to the human subject when the polygenic score is greater than the reference polygenic score.
9 . The method of claim 1 , further comprising:
detecting, in the sample, alleles at each of SNP rs9847006 in ULK4, SNP rs56298756 in USP15, SNP rs2118181 in FBN1, SNP rs62053262 in WWP2, and SNP rs6974735 in ELN;
calculating a polygenic score based on the G allele at the SNP rs1441358 in THSD4 and the detected alleles, wherein the polygenic score is increased by detection of a T allele at the SNP rs9847006 in ULK4, a T allele at the SNP rs56298756 in USP15, a C allele at the SNP rs2118181 in FBN1, a C allele at the SNP rs62053262 in WWP2, and an A allele at the SNP rs6974735 in ELN; and
determining that the human subject is at a further increased risk for the aneurysm of the ascending thoracic aorta when the polygenic score is greater than a reference polygenic score calculated from a population of subjects who do not have thoracic aortic aneurysms.