Table 3.
Genome-wide association and next-generation sequencing studies of BAV
| Author | Type | Cases | Controls | Findings | Reference |
|---|---|---|---|---|---|
| Hanchard | GWAS | 778 non-syndromic left-sided lesions cases | 2756 patients without left-sided lesions from the high-density SNP association analysis of melanoma: case-control and outcomes investigation and from the GWAS of Parkinson disease: genes and environment | Locus 20q11 associated with BAV, MYH7B and MIR499A as candidate genes | 61 |
| Yang | GWAS | 466 non-syndromic BAV (83% TAA) attending cardiac surgery clinic at the University of Michigan Frankel Cardiovascular Center | 4660 age, sex and ethnicity matched controls from the Michigan Genomics Initiative | Noncoding variants near GATA4 associated with BAV | 78 |
| Fulmer | GWAS | 2131 non-syndromic BAV cases | 2728 patients without BAV from the Framingham Heart Study cohort | 15 SNPs associated with BAV, including EXOC4 | 79 |
| Helgadotir | GWAS | 208 non-syndromic BAV (Iceland, Sweden, USA) | 25139 controls (Iceland deCODE database, Stockholm POLCA/Olivia study, Michigan Genomics Initiative, Framingham Heart Study and National Institute of Neurological Disorders and Stroke) | PALMD intergenic and TEX41 intronic variants associated with BAV | 128 |
| Bjornsson | GWAS | 120 Icelandic non-syndromic CoA cases (75% with BAV) | 355166 disease-free individuals randomly selected from Icelandic genealogical databases at deCODE | Rare missense mutations of MYH6 in BAV cases | 81 |
| LeMaire | GWAS (3 stages) | 765 non-syndromic TAD, 385 non-syndromic TAD (192 BAV), 163 non-syndromic TAD (157 BAV) | 1355, 159 and 476 controls from Wellcome T rust Case-Control Consortium 1958 Birth Cohort and US National Institute of Neurological Disorders and Stroke | Common FBN1 variants associated with TAD, with or without BAV | 124 |
| Wooten | Modified GWAS | 68 non-syndromic BAV | 830 controls from Illumina iControlDB and 7 BAV negative familial controls | Rare AXIN1/PDIA2 haplotype associated with BAV | 80 |
| Gago-Dlaz | Population-based NGS | 565 Spanish non-syndromic BAV cases (none with cardiac or ascending aortic surgery) | 484 controls attending primary health care centers in Galicia and from Plataforma en Red Banco Nacional de ADN Carlos III | No significant associations with BAV | 83 |
| Guo | Family-based NGS | 34 family members with TAA (BAV 47%) | MAT2A mutations segregate with BAV and HTAD | 85 | |
| Gould | Family-based NGS | 286 family members with BAV/TAA | 193 unrelated controls | ROBO4 mutations segregate with BAV and HTAD and are enriched in non-syndromic cases. | 86 |
BAV: bicuspid aortic valve; GWAS: genome-wide association study; NGS: next generation sequencing; SNP: single-nucleotide polymorphism; TAA: thoracic aortic aneurysm; TAD: thoracic aortic aneurysm and dissection.