Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis

OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations.

METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline.

RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses.

CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.

Reintegração paisagística de infraestruturas rodoviárias: o caso da Estrada Nacional 122 e do Itinerário Complementar 27

Dissertação de Mestrado, Arquitetura Paisagista, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Executive order no. 87-27

This executive order by Governor Carroll A Campbell, Jr. orders an election be held in Woodford to elect a new city council member.

Letter, Elmwood, SC, from Annie Causey Walsh, Chesterfield, SC, 1869 April 27

This letter is from Annie, niece of Sarah Spencer, to her cousin. She writes of the well being of her family, her relations, and how she is currently living.

Andor Foldes, Lecture-Recital, July 27, 1945

Concert program for Andor Foldes, July 27, 1945

University Chorale in a Program for the American Choral Directors Northwest Division Convention, February 27, 1976

Concert program for University Chorale, February 27, 1976

Eva Heinitz and Malcolm Hamilton, Recital for Viola da Gamba and Harpsichord, January 27, 1966

Concert Program for Eva Heinitz and Malcolm Hamilton, Recital for Viola da Gamba and Harpsichord, January 27, 1966

The Madrigal Singers, May 27, 1987

Concert Program for The Madrigal Singers, May 27, 1987

Halloween Organ Recital October 27, 2000

Concert Program for Halloween Organ Recital October 27, 2000