A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

A method to approximate the inverse of a part of the additive relationship matrix.

Single-step genomic predictions need the inverse of the part of the additive relationship matrix between genotyped animals (A22 ). Gains in computing time are feasible with an algorithm that sets up the sparsity pattern of A22-1 (SP algorithm) using pedigree searches, when A22-1 is close to sparse. The objective of this study is to present a modification of the SP algorithm (RSP algorithm) and to assess its use in approximating A22-1 when the actual A22-1 is dense. The RSP algorithm sets up a restricted sparsity pattern of A22-1 by limiting the pedigree search to a maximum number of searched branches. We have tested its use on four different simulated genotyped populations, from 10 000 to 75 000 genotyped animals. Accuracy of approximation is tested by replacing the actual A22-1 by its approximation in an equivalent mixed model including only genotyped animals. Results show that limiting the pedigree search to four branches is enough to provide accurate approximations of A22-1, which contain approximately 80% of zeros. Computing approximations is not expensive in time but may require a great amount of memory (at maximum, approximately 81 min and approximately 55 Gb of RAM for 75 000 genotyped animals using parallel processing on four threads).

Estimation of dominance variance for live body weight in a crossbred population of pigs.

The objective of this study was to estimate the dominance variance for repeated live BW records in a crossbred population of pigs. Data were provided by the Walloon Pig Breeding Association and included 22,197 BW records of 2,999 crossbred Piétrain × Landrace K+ pigs from 50 to 210 d of age. The BW records were standardized and adjusted to 210 d of age for analysis. Three single-trait random regression animal models were used: Model 1 without parental subclass effect, Model 2 with parental subclasses considered unrelated, and Model 3 with the complete parental dominance relationship matrix. Each model included sex, contemporary group, and heterosis as fixed effects as well as additive genetic, permanent environment, and residual as random effects. Variance components and their SE were estimated using a Gibbs sampling algorithm. Heritability tended to increase with age: from 0.50 to 0.64 for Model 1, from 0.19 to 0.42 for Model 2, and from 0.31 to 0.53 for Model 3. Permanent environmental variance tended to decrease with age and accounted for 29 to 44% of total variance for Model 1, 29 to 37% of total variance for Model 2, and 34 to 51% of total variance for Model 3. Residual variance explained <10% of total variance for the 3 models. Dominance variance was computed as 4 times the estimated parental subclass variance. Dominance variance accounted for 22 to 40% of total variance for Model 2 and 5 to 11% of total variance for Model 3, with a decrease with age for both models. Results showed that dominance effects exist for growth traits in pigs and may be reasonably large. The use of the complete dominance relationship matrix may improve the estimation of additive genetic variances and breeding values. Moreover, a dominance effect could be especially useful in selection programs for individual matings through the use of specific combining ability to maximize growth potential of crossbred progeny.

A recursive algorithm for decomposition and creation of the inverse of the genomic relationship matrix.

Some genomic evaluation models require creation and inversion of a genomic relationship matrix (G). As the number of genotyped animals increases, G becomes larger and thus requires more time for inversion. A single-step genomic evaluation also requires inversion of the part of the pedigree relationship matrix for genotyped animals (A(22)). A strategy was developed to provide an approximation of the inverse of GG˜(-1) that may also be applied to the inverse of A(22)(A˜(22)(-1)) The algorithm proceeds by creation of an incomplete Cholesky factorization (T˜(-1)) of G(-1). For this purpose, a genomic relationship threshold determines whether 2 animals are closely related. For any animal, the sparsity pattern of the corresponding line in T˜(-1) will thus gather elements corresponding to all close relatives of that animal. Any line of T˜(-1) is filled in with resulting estimators of the least-squares regression of genomic relationships between close relatives on genomic relationship between the animal considered and those close relatives. The G˜(-1) was computed as the matrix product (T˜(-1))(')D(-1)T˜(-1), where D(-1) is a diagonal matrix. Then, T(-1)G(T(-1))(') resulted in a new matrix that is close to diagonal and also needs to be inverted. The inverse of that matrix was approximated with the same decomposition as for approximation of the inverse of G(G˜(-1)) and the procedure was repeated in successive rounds of recursion until a matrix was obtained that was close enough to diagonal to be inverted element by element. Two applications of the approximation algorithm were tested in a single-step genomic evaluation of US Holstein final score, and correlation coefficients between estimated breeding values based on either real or approximated G(-1) were compared. Approximations came closer to G(-1) as the number of recursion rounds increased. Approximations were even more accurate and expected to be faster for A(22). Timesaving strategies are needed to reduce the computing time required for the algorithm.

Evolution of postural stability after subthalamic nucleus stimulation in Parkinson's disease: a combined clinical and posturometric study.

OBJECTIVES: The occurrence of postural and balance disorders is a frequent feature in advanced forms of Parkinson's disease (PD). However, the pathological substrate of these disturbances is poorly understood. METHODS: In the present work, we investigated the evolution of posturometric parameters [center of pressure (CoP) displacement and CoP area] and axial scores between the pre-operative period and 3 months post-operative in seven PD patients who underwent bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). RESULTS: After surgery, the patients leaned backwards much more regardless of the STN stimulation, suggesting that surgery could have a deleterious effect on postural adaptation. During the post-operative period, the improvement in axial and postural scores was similar under levodopatherapy and DBS. On the other hand, DBS of the STN significantly reduced the CoP displacement and the CoP area, whereas levodopatherapy tended only to reduce the CoP displacement and to increase the CoP area significantly. CONCLUSIONS: These data suggest that DBS of the STN and levodopa do not act on the same neurological systems involved in posture regulation. DBS of the STN could improve posture via a direct effect on the pedunculopontine nucleus, which is known to be involved in posture regulation.

Early changes in isokinetic lower limb muscle strength in recovering geriatric subjects on the basis of nutritional status.

BACKGROUND: In older people, the decrease in muscle mass and strength has a bad effect on functional status. Malnutrition and lack of physical activity exacerbate this phenomenon. OBJECTIVE: The main purpose of this study was to estimate isokinetic lower limb muscle strength in recovering older subjects on the basis of nutritional status. DESIGN: Twenty-eight elderly subjects hospitalized for an acute event (85.8 +/- 6 years), including 16 malnourished, were enrolled in this study when clinically stable (T0). Re-assessment at one-month was performed in nine after oral supplementation and conventional physiotherapy (T1). The Maximal Peak Torque (MPT) of the ankle plantar flexors was estimated in concentric mode at 30 and 60 degrees /s. The MPT of the knee flexors and extensors was evaluated in the same mode at 30 degrees /s, 60 degrees /s and 120 degrees /s. All patients underwent a nutritional examination with anthropometric measures, dietary intake survey, biochemical indexes and determination of the medial gastrocnemius volume by magnetic resonance imaging. RESULTS: At T0, whatever the muscle group tested (except at 120 degrees /s for the knee), the MPT appeared significantly lower in the malnourished group. At T1, the increase in MPT (plantar flexors) in malnourished patients was greater at 60 degrees /s (+23.8 %) than at 30 degrees /s (+14.8 %). Correlations between MPT and nutritional parameters were observed in the malnourished group only at T1 and in the normal-nourished group. CONCLUSION: Isokinetic assessment seems to be a pertinent method to estimate lower limb muscle strength in older and frail subjects. Early modifications in strength were observed in malnourished patients who received oral supplementation and physiotherapy.

Functional and metabolic early changes in calf muscle occurring during nutritional repletion in malnourished elderly patients.

BACKGROUND: Metabolic alterations in skeletal muscle associated with malnutrition and the potential reversibility of such alterations during refeeding are not fully understood. OBJECTIVE: We characterized early changes in muscle during refeeding in malnourished, hospitalized elderly subjects. DESIGN: Muscle function, metabolism, and mass were evaluated in 24 clinically stable patients (11 were malnourished) by using isokinetic plantar flexor torque measurements and nuclear magnetic resonance (NMR) imaging for medial gastrocnemius mass assessment and 31P and 13C NMR spectroscopy for inorganic phosphate (Pi), phosphocreatine, and glycogen quantitation. RESULTS: Malnourished subjects had lower muscle mass (P < 0.02) and tended to have lower strength than did control subjects. In malnourished subjects, muscle strength increased after refeeding (P < 0.01) whereas muscle mass was unchanged. The ratio of Pi to ATP was lower in malnourished than in control subjects (P < 0.001) and increased during refeeding (P < 0.01). The mean ratio of phosphocreatine to ATP was lower in malnourished than in control subjects (P < 0.01) and increased to control values after refeeding. Muscle glycogen showed a scattered distribution for malnourished subjects; the mean value did not differ significantly from that of control subjects, either at baseline or after refeeding. CONCLUSIONS: The lower ratio of phosphocreatine to ATP in malnourished subjects could have resulted from either lower total muscle creatine or reduced oxidative capacities. High or normal glycogen associated with a low Pi-to-ATP ratio in malnourished subjects suggested preferential use of lipid over carbohydrate for energy supply, which is known to reduce muscle performance. The data suggest that normalization of muscle metabolite content after refeeding improves muscle strength in malnourished subjects.