Ana Marušić

Bio: Ana Marušić is an academic researcher from University of Split. The author has contributed to research in topics: Medicine & Clinical trial. The author has an hindex of 55, co-authored 451 publications receiving 17942 citations. Previous affiliations of Ana Marušić include Norwegian Institute of Public Health & Cochrane Collaboration.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Mentoring in academic medicine: a systematic review.

Abstract: ContextMentoring, as a partnership in personal and professional growth and development, is central to academic medicine, but it is challenged by increased clinical, administrative, research, and other educational demands on medical faculty. Therefore, evidence for the value of mentoring needs to be evaluated.ObjectiveTo systematically review the evidence about the prevalence of mentorship and its relationship to career development.Data SourcesMEDLINE, Current Contents, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, PsycINFO, and Scopus databases from the earliest available date to May 2006.Study Selection and Data ExtractionWe identified all studies evaluating the effect of mentoring on career choices and academic advancement among medical students and physicians. Minimum inclusion criteria were a description of the study population and availability of extractable data. No restrictions were placed on study methods or language.Data SynthesisThe literature search identified 3640 citations. Review of abstracts led to retrieval of 142 full-text articles for assessment; 42 articles describing 39 studies were selected for review. Of these, 34 (87%) were cross-sectional self-report surveys with small sample size and response rates ranging from 5% to 99%. One case-control study nested in a survey used a comparison group that had not received mentoring, and 1 cohort study had a small sample size and a large loss to follow-up. Less than 50% of medical students and in some fields less than 20% of faculty members had a mentor. Women perceived that they had more difficulty finding mentors than their colleagues who are men. Mentorship was reported to have an important influence on personal development, career guidance, career choice, and research productivity, including publication and grant success.ConclusionsMentoring is perceived as an important part of academic medicine, but the evidence to support this perception is not strong. Practical recommendations on mentoring in medicine that are evidence-based will require studies using more rigorous methods, addressing contextual issues, and using cross-disciplinary approaches.

Clinical Trial Registration A Statement From the International Committee of Medical Journal Editors

Abstract: Altruism and trust lie at the heart of research on human subjects. Altruistic individuals volunteer for research because they trust that their participation will contribute to improved health for others and that researchers will minimize risks to participants. In return for the altruism and trust that make clinical research possible, the research enterprise has an obligation to conduct research ethically and to report it honestly. Honest reporting begins with revealing the existence of all clinical studies, even those that reflect unfavorably on a research sponsor's product. Unfortunately, selective reporting of trials does occur, and it distorts the body of evidence . . .

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement

Abstract: Moher and colleagues introduce PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses. Us...