ABSTRACT
Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
Subject(s)
Aortic Aneurysm, Abdominal/genetics , Chromosomes, Human, Pair 9 , Genetic Variation , Intracranial Aneurysm/genetics , Myocardial Infarction/genetics , Adult , Aged , Alleles , Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/physiopathology , Case-Control Studies , Chi-Square Distribution , Female , Gene Frequency , Genetic Markers , Haplotypes , Homozygote , Humans , Intracranial Aneurysm/physiopathology , Likelihood Functions , Linkage Disequilibrium , Male , Middle Aged , Myocardial Infarction/physiopathology , Odds Ratio , Polymorphism, Single Nucleotide , Prevalence , Probability , Risk Factors , Sequence Analysis, DNA , White PeopleABSTRACT
We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.
