The Metabolic Syndrome in Men study: a resource for studies of metabolic and cardiovascular diseases

Laakso, Markku; Kuusisto, Johanna; Stančáková, Alena; Kuulasmaa, Teemu; Pajukanta, Päivi; Lusis, Aldons J.; Collins, Francis S.; Mohlke, Karen L.; Boehnke, Michael

doi:10.1194/jlr.o072629

Cited by 178 publications

(181 citation statements)

References 98 publications

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“…We also evaluated associations between rs11708067 and 21 glucose- and insulin-related traits from ∼8,500 individuals without diabetes from the Metabolic Syndrome in Men (METSIM) study (Supplementary Table 2) (24,25). Trait values containing skewed distributions were log transformed, and we winsorized all traits at 5 SDs from the mean.…”

Section: Methodsmentioning

confidence: 99%

A Type 2 Diabetes–Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus

Roman¹,

Cannon²,

Vadlamudi³

et al. 2017

Diabetes

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Molecular mechanisms remain unknown for most type 2 diabetes genome-wide association study identified loci. Variants associated with type 2 diabetes and fasting glucose levels reside in introns of ADCY5, a gene that encodes adenylate cyclase 5. Adenylate cyclase 5 catalyzes the production of cyclic AMP, which is a second messenger molecule involved in cell signaling and pancreatic β-cell insulin secretion. We demonstrated that type 2 diabetes risk alleles are associated with decreased ADCY5 expression in human islets and examined candidate variants for regulatory function. rs11708067 overlaps a predicted enhancer region in pancreatic islets. The type 2 diabetes risk rs11708067-A allele showed fewer H3K27ac ChIP-seq reads in human islets, lower transcriptional activity in reporter assays in rodent β-cells (rat 832/13 and mouse MIN6), and increased nuclear protein binding compared with the rs11708067-G allele. Homozygous deletion of the orthologous enhancer region in 832/13 cells resulted in a 64% reduction in expression level of Adcy5, but not adjacent gene Sec22a, and a 39% reduction in insulin secretion. Together, these data suggest that rs11708067-A risk allele contributes to type 2 diabetes by disrupting an islet enhancer, which results in reduced ADCY5 expression and impaired insulin secretion.

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Section: Methodsmentioning

confidence: 99%

A Type 2 Diabetes–Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus

Roman¹,

Cannon²,

Vadlamudi³

et al. 2017

Diabetes

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“…In this real example, we considered single-variant meta-analyses of three T2D GWASs: FUSION (1,142 cases vs. 1,155 controls; unrelated Finnish samples) (Scott et al, 2007), METSIM (673 cases vs. 2,667 controls; unrelated Finnish male samples) (Laakso et al, 2017), and MGI (1,942 cases vs. 14,553 controls; unrelated European American samples). These three unbalanced GWASs have various case-control ratios (0.98, 0.24, 0.13) and multi-ethnic samples (Supplementary Figures 15–16).…”

Section: Resultsmentioning

confidence: 99%

“…Three GWASs of type 2 diabetes (T2D) were considered in this paper: the Finland-United States Investigation of NIDDM genetics (FUSION) study (Scott et al, 2007), METabolic Syndrome In Men (METSIM) study (Laakso et al, 2017), and Michigan Genomics Initiative (MGI) study. We analyzed 2,297 unrelated Finnish samples (1,142 cases vs. 1,155 controls) in FUSION, 3,340 unrelated Finnish samples (673 cases vs. 2,667 controls) in METSIM, and 16,495 unrelated European American samples (1,942 cases vs. 14,553 controls) in MGI.…”

Section: Methodsmentioning

confidence: 99%

Improved score statistics for meta‐analysis in single‐variant and gene‐level association studies

Yang

Chen

Abecasis

2018

Genetic Epidemiology

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Meta-analysis is now an essential tool for genetic association studies, allowing them to combine large studies and greatly accelerating the pace of genetic discovery. Although the standard meta-analysis methods perform equivalently as the more cumbersome joint analysis under ideal settings, they result in substantial power loss under unbalanced settings with various case-control ratios. Here, we investigate the power loss problem by the standard meta-analysis methods for unbalanced studies, and further propose novel meta-analysis methods performing equivalently to the joint analysis under both balanced and unbalanced settings. We derive improved meta-score-statistics that can accurately approximate the joint-score-statistics with combined individual-level data, for both linear and logistic regression models, with and without covariates. In addition, we propose a novel approach to adjust for population stratification by correcting for known population structures through minor allele frequencies. In the simulated gene-level association studies under unbalanced settings, our method recovered up to 85% power loss caused by the standard methods. We further showed the power gain of our methods in gene-level tests with 26 unbalanced studies of age-related macular degeneration . In addition, we took the meta-analysis of three unbalanced studies of type 2 diabetes as an example to discuss the challenges of meta-analyzing multi-ethnic samples. In summary, our improved meta-score-statistics with corrections for population stratification can be used to construct both single-variant and gene-level association studies, providing a useful framework for ensuring well-powered, convenient, cross-study analyses.

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“…El Índice de Masa Corporal (IMC) es el método más empleado para evaluar sobrepeso y obesidad, pero ha sido cuestionado porque no siempre refleja la verdadera cantidad de GC en personas con masa muscular alta o muy baja [13][14][15] . De acuerdo con Madeira y cols.…”

Section: Cholesterol Education Program (Ncep) Adult Treatment Panel unclassified

Área bajo curva ROC de Porcentaje de grasa corporal como estimativo de Síndrome metabólico en adultos de Barranquilla, Colombia

Olaciregui¹,

Moranth

Lechuga

2017

Rev Esp Nutr Hum Diet

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[ahead of print]Freely available online -OPEN ACCESS La Revista Española de Nutrición Humana y Dietética se esfuerza por mantener a un sistema de publicación continua, de modo que los artículos se publican antes de su formato final (antes de que el número al que pertenecen se haya cerrado y/o publicado). De este modo, intentamos poner los artículos a disposición de los lectores/usuarios lo antes posible.The Spanish Journal of Human Nutrition and Dietetics strives to maintain a continuous publication system, so that the articles are published before its final format (before the number to which they belong is closed and/or published). In this way, we try to put the articles available to readers/users as soon as possible. Las medias de grasa corporal fueron mayores en sujetos con SM independientemente del método utilizado (p<0,05). Las áreas bajo curva ROC oscilaron entre 63% y 76,9%, con sensibilidades entre 50% y 85%, y especificidades entre 51% y 78%. Mediante Lean-cintura y el consenso de AHA se obtuvo el valor más alto del área bajo la curva (0,77; punto de corte: 37,1; sensibilidad: 60,8; especificidad: 78,8%) y utilizando Siri y el consenso armonizado se obtuvo el valor más bajo (0,63; punto de corte: 28,5; sensibilidad: 80%; especificidad: 42,5%). Conclusiones: El análisis de curvas ROC permite identificar la relación entre grasa corporal y síndrome metabólico, y podría emplearse como tamizaje, teniendo en cuenta que los valores de sensibilidad y especificidad dependen de las mediciones antropométricas y las ecuaciones empleadas. Revista Española de Nutrición

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The Metabolic Syndrome in Men study: a resource for studies of metabolic and cardiovascular diseases

Cited by 178 publications

References 98 publications

A Type 2 Diabetes–Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus

A Type 2 Diabetes–Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus

Improved score statistics for meta‐analysis in single‐variant and gene‐level association studies

Área bajo curva ROC de Porcentaje de grasa corporal como estimativo de Síndrome metabólico en adultos de Barranquilla, Colombia

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