Browsing by Author "Ferrucci, Luigi"

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    Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory.
    (Behavior genetics, 2014-07) van den Berg, Stéphanie M; de Moor, Marleen HM; McGue, Matt; Pettersson, Erik; Terracciano, Antonio; Verweij, Karin JH; Amin, Najaf; Derringer, Jaime; Esko, Tõnu; van Grootheest, Gerard; Hansell, Narelle K; Huffman, Jennifer; Konte, Bettina; Lahti, Jari; Luciano, Michelle; Matteson, Lindsay K; Viktorin, Alexander; Wouda, Jasper; Agrawal, Arpana; Allik, Jüri; Bierut, Laura; Broms, Ulla; Campbell, Harry; Smith, George Davey; Eriksson, Johan G; Ferrucci, Luigi; Franke, Barbera; Fox, Jean-Paul; de Geus, Eco JC; Giegling, Ina; Gow, Alan J; Grucza, Richard; Hartmann, Annette M; Heath, Andrew C; Heikkilä, Kauko; Iacono, William G; Janzing, Joost; Jokela, Markus; Kiemeney, Lambertus; Lehtimäki, Terho; Madden, Pamela AF; Magnusson, Patrik KE; Northstone, Kate; Nutile, Teresa; Ouwens, Klaasjan G; Palotie, Aarno; Pattie, Alison; Pesonen, Anu-Katriina; Polasek, Ozren; Pulkkinen, Lea; Pulkki-Råback, Laura; Raitakari, Olli T; Realo, Anu; Rose, Richard J; Ruggiero, Daniela; Seppälä, Ilkka; Slutske, Wendy S; Smyth, David C; Sorice, Rossella; Starr, John M; Sutin, Angelina R; Tanaka, Toshiko; Verhagen, Josine; Vermeulen, Sita; Vuoksimaa, Eero; Widen, Elisabeth; Willemsen, Gonneke; Wright, Margaret J; Zgaga, Lina; Rujescu, Dan; Metspalu, Andres; Wilson, James F; Ciullo, Marina; Hayward, Caroline; Rudan, Igor; Deary, Ian J; Räikkönen, Katri; Arias Vasquez, Alejandro; Costa, Paul T; Keltikangas-Järvinen, Liisa; van Duijn, Cornelia M; Penninx, Brenda WJH; Krueger, Robert F; Evans, David M; Kaprio, Jaakko; Pedersen, Nancy L; Martin, Nicholas G; Boomsma, Dorret I
    Mega- or meta-analytic studies (e.g. genome-wide association studies) are increasingly used in behavior genetics. An issue in such studies is that phenotypes are often measured by different instruments across study cohorts, requiring harmonization of measures so that more powerful fixed effect meta-analyses can be employed. Within the Genetics of Personality Consortium, we demonstrate for two clinically relevant personality traits, Neuroticism and Extraversion, how Item-Response Theory (IRT) can be applied to map item data from different inventories to the same underlying constructs. Personality item data were analyzed in >160,000 individuals from 23 cohorts across Europe, USA and Australia in which Neuroticism and Extraversion were assessed by nine different personality inventories. Results showed that harmonization was very successful for most personality inventories and moderately successful for some. Neuroticism and Extraversion inventories were largely measurement invariant across cohorts, in particular when comparing cohorts from countries where the same language is spoken. The IRT-based scores for Neuroticism and Extraversion were heritable (48 and 49 %, respectively, based on a meta-analysis of six twin cohorts, total N = 29,496 and 29,501 twin pairs, respectively) with a significant part of the heritability due to non-additive genetic factors. For Extraversion, these genetic factors qualitatively differ across sexes. We showed that our IRT method can lead to a large increase in sample size and therefore statistical power. The IRT approach may be applied to any mega- or meta-analytic study in which item-based behavioral measures need to be harmonized.
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    fastMitoCalc: an ultra-fast program to estimate mitochondrial DNA copy number from whole-genome sequences
    (Bioinformatics, 2017-05-01) Qian, Yong; Butler, Thomas J; Opsahl-Ong, Krista; Giroux, Nicholas S; Sidore, Carlo; Nagaraja, Ramaiah; Cucca, Francesco; Ferrucci, Luigi; Abecasis, Gonçalo R; Schlessinger, David; Ding, Jun
    Abstract Mitochondrial DNA (mtDNA) copy number is tightly regulated in tissues, and is both a critical determinant of mitochondrial function and a potential biomarker for disease. We and other groups have shown that the mtDNA copy number per cell can be directly estimated from whole-genome sequencing. The computation is based on the rationale that sequencing coverage should be proportional to the underlying DNA copy number for autosomal and mitochondrial DNA, and most computing time is spent calculating the average autosomal DNA coverage across ∼3 billion bases. That makes analyzing tens of thousands of available samples very slow. Here we present fastMitoCalc, which takes advantage of the indexing of sequencing alignment files and uses a randomly selected small subset (0.1%) of the nuclear genome to estimate autosomal DNA coverage accurately. It is more than 100 times faster than current programs. fastMitoCalc also provides an option to estimate copy number using a single autosomal chromosome, which could also achieve high accuracy but is slower. Using fastMitoCalc, it becomes much more feasible now to conduct analyses on large-scale consortium data to test for association of mtDNA copy number with quantitative traits or nuclear variants. Availability and Implementation fastMitoCalc is available at https://lgsun.irp.nia.nih.gov/hsgu/software/mitoAnalyzer/index.html Supplementary information Supplementary data are available at Bioinformatics online.
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    Sarcopenia: A Time for Action. An SCWD Position Paper.
    (Journal of cachexia, sarcopenia and muscle, 2019-10) Bauer, Juergen; Morley, John E; Schols, Annemie MWJ; Ferrucci, Luigi; Cruz-Jentoft, Alfonso J; Dent, Elsa; Baracos, Vickie E; Crawford, Jeffrey A; Doehner, Wolfram; Heymsfield, Steven B; Jatoi, Aminah; Kalantar-Zadeh, Kamyar; Lainscak, Mitja; Landi, Francesco; Laviano, Alessandro; Mancuso, Michelangelo; Muscaritoli, Maurizio; Prado, Carla M; Strasser, Florian; von Haehling, Stephan; Coats, Andrew JS; Anker, Stefan D
    The term sarcopenia was introduced in 1988. The original definition was a "muscle loss" of the appendicular muscle mass in the older people as measured by dual energy x-ray absorptiometry (DXA). In 2010, the definition was altered to be low muscle mass together with low muscle function and this was agreed upon as reported in a number of consensus papers. The Society of Sarcopenia, Cachexia and Wasting Disorders supports the recommendations of more recent consensus conferences, i.e. that rapid screening, such as with the SARC-F questionnaire, should be utilized with a formal diagnosis being made by measuring grip strength or chair stand together with DXA estimation of appendicular muscle mass (indexed for height2). Assessments of the utility of ultrasound and creatine dilution techniques are ongoing. Use of ultrasound may not be easily reproducible. Primary sarcopenia is aging associated (mediated) loss of muscle mass. Secondary sarcopenia (or disease-related sarcopenia) has predominantly focused on loss of muscle mass without the emphasis on muscle function. Diseases that can cause muscle wasting (i.e. secondary sarcopenia) include malignant cancer, COPD, heart failure, and renal failure and others. Management of sarcopenia should consist of resistance exercise in combination with a protein intake of 1 to 1.5 g/kg/day. There is insufficient evidence that vitamin D and anabolic steroids are beneficial. These recommendations apply to both primary (age-related) sarcopenia and secondary (disease related) sarcopenia. Secondary sarcopenia also needs appropriate treatment of the underlying disease. It is important that primary care health professionals become aware of and make the diagnosis of age-related and disease-related sarcopenia. It is important to address the risk factors for sarcopenia, particularly low physical activity and sedentary behavior in the general population, using a life-long approach. There is a need for more clinical research into the appropriate measurement for muscle mass and the management of sarcopenia. Accordingly, this position statement provides recommendations on the management of sarcopenia and how to progress the knowledge and recognition of sarcopenia.
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    Sarcopenia: no consensus, no diagnostic criteria, and no approved indication-How did we get here?
    (GeroScience, 2024-02) Evans, William J; Guralnik, Jack; Cawthon, Peggy; Appleby, James; Landi, Francesco; Clarke, Lindsay; Vellas, Bruno; Ferrucci, Luigi; Roubenoff, Ronenn
    In addition to the role of skeletal muscle in movement and locomotion, muscle plays a critical role in a broad array of metabolic processes that can contribute to improved health or risk of disease. The age-associated loss of muscle has been termed sarcopenia. The muscle is the primary site of insulin-stimulated glucose disposal and the largest component of basal metabolic rate, directly and indirectly affects bone density, produces myokines with pleiotropic effect on muscle and other tissues including the brain, and stores essential amino acids essential for the maintenance of protein synthesis during periods of reduced food intake and stress. As such, not surprisingly deterioration of skeletal muscle health, typically operationalized as decline of muscle mass and muscle strength is both a powerful risk factor and main consequence of chronic diseases, disability, and loss of independence, and it is one of the strongest risk factors for mortality. However, skeletal muscle remains one of the most plastic of all tissues, with rapid changes in rates of protein synthesis and degradation in response to physical activity and inactivity, inflammation, and nutritional and hormonal status. This has made the development of pharmacological therapies to increase muscle mass (or prevent loss), an important goal for decades. However, while remarkable advances in the understanding of molecular and cellular regulation of muscle protein metabolism have occurred recently, there are no approved drugs for the treatment of sarcopenia, the loss of skeletal muscle affecting millions of older people. The goal of this paper is to describe the possible reasons for the lack of new and effective pharmacotherapies to treat one of the most important risk factors for age-associated disease and loss of independence.
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    Unexplained anemia of aging: Etiology, health consequences, and diagnostic criteria.
    (Journal of the American Geriatrics Society, 2022-03) Guralnik, Jack; Ershler, William; Artz, Andrew; Lazo-Langner, Alejandro; Walston, Jeremy; Pahor, Marco; Ferrucci, Luigi; Evans, William J

    Background

    Up to 15% of people aged 60 and over are anemic, and the prevalence of anemia increases with age. In older men and women, anemia is associated with increases in the risk of death and all-cause hospitalization, poor functional capacity, quality of life, and depression.

    Methods and results

    We reviewed the literature describing anemia in aging populations, focusing on the specific diagnostic criteria of anemia and potential causes in older men and women. Even after extensive etiologic workup that involves careful medical history, physical examination, laboratory measurements, and additional studies such as bone marrow biopsy, anemia of aging is unexplained in up to 40% of older patients with anemia. As a result, treatment options remain limited.

    Conclusions

    The prevalence of unexplained anemia of aging (UAA; also called unexplained anemia of the elderly, UAE), its deleterious impacts on health, physical function, and quality of life, and the lack of effective treatment or therapy guidelines represent a compelling unmet clinical need. In this review and consensus document, we discuss the scope of the problem, possible causes of UAA, diagnostic criteria, and potential treatment options. Because even mild anemia is strongly linked to poor clinical outcomes, it should receive clinical attention rather than simply being considered a normal part of aging.