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Genetic studies of body mass index yield new insights for obesity biology
Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (
P
< 5 × 10
−8
), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis.
Genetic correlates of obesity
In the second of two Articles in this issue from the GIANT Consortium, Elizabeth Speliotes and collegues conducted a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), commonly used to define obesity and assess adiposity, to find 97 BMI-associated loci, of which 56 were novel. Many of these loci have significant effects on other metabolic phenotypes. The 97 loci account for about 2.7% of BMI variation, and genome-wide estimates suggest common variation accounts for more than 20% of BMI variation. Pathway analyses implicate the central nervous system in obesity susceptibility including synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Journal Article
Primary Sjögren’s Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development
To study the clinical, serological and histologic features of primary Sjögren's syndrome (pSS) patients with early (young ≤35 years) or late (old ≥65 years) onset and to explore the differential effect on lymphoma development.
From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups.
Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud's phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11-3.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34-8.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years.
Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time.
Journal Article
Gender difference in prevalence of hypertension among Indians across various age-groups: a report from multiple nationally representative samples
Background
Prevalence of hypertension increases with age, but there is a general perception in India that women are less affected at every stage of life, although empiric evidence hardly exists regarding gender difference in hypertension in Indians of different ages. Therefore, we aimed to examine the gender difference in hypertension among Indians across various age-groups; and the contribution of variation in body mass index (BMI) to this difference.
Methods
Data were analysed after combining National Family Health Survey 4 (
n
= 294,584 aged 35–49 years) and Study of Ageing and Health wave 2 (
n
= 7118 aged 50 + years) datasets (NFHS-SAGE). Longitudinal Ageing Study of India (LASI) dataset (
n
= 65,900 aged > 45years) was analysed to replicate the results. Hypertension was defined if systolic and diastolic blood pressure was > 89 and/or > 139 respectively and/or if there was a history of anti-hypertensive medication. Descriptive summaries were tabulated and plotted to examine the gender difference in hypertension in various age-groups (35–39,40–44, 45–49, 50–54, 55–59, 60–64, 65–69, ≥ 70). Odds Ratios (ORs) from logistic regression models estimated the age gradient of hypertension and their male-female difference, adjusted for Body Mass Index (BMI).
Results
Males had a higher prevalence of hypertension up to 50 years; after that, females had higher rates. The estimates of age gradient, expressed as ORs, were 1.02 (1.02, 1.02) in males versus 1.05(1.05, 1.06) in females (
p
< 0.001) in NFHS-SAGE and 1.01(1.01, 1.02) in males versus 1.04(1.03, 1.04)in females (
p
< 0.001) in LASI;these differences marginally changed after adjustment with BMI.
Conclusion
This is perhaps the first study to comprehensively demonstrate that cardio-metabolic risk in Indian females surpasses males after 50 years of age, “busting the myth” that Indian females are always at much lower risk than males; and this evidence should inform the Indian healthcare system to prioritise older women for screening and treatment of hypertension.
Journal Article
Mitigating against relative age effects in youth Track & Field: Validating corrective adjustment procedures across multiple events
With the aim to better identify talented Track & Field performance development, this study estimated the relationships between chronological (decimal) age with 60-m sprint, high jump, triple jump, and pole vault performance. Then, to mitigate against expected Relative Age Effects (RAEs), Corrective Adjustment Procedures (CAPs) were applied to an independent sample.
Mixed-longitudinal design examining public data between 2005 and 2019.
The performances of 5339 Italian sprinters and jumpers (53.1 %) spanning 11.01–17.99 years of age were examined, with trendlines between chronological age and performance established. Related to an independent sample (N = 40,306; female 45.5 %), trendlines were then utilised to apply CAPs and adjust individual performance. Considering raw and adjusted performance data, RAE distributions were examined for the top 25 % and 10 % performers.
For all male and female events, quadratic models best summarised the relationships between chronological age and performance (R2 = 0.74–0.89). When examining independent athletes in similar event, RAEs were more pronounced in males (Cramer's V = 0.35–0.14) than females (Cramer's V = 0.29–0.07). For both sexes, RAE magnitude decreased with age and increased according to performance level (i.e., Top25%–Top10%). However, following CAP applications, RAEs were reduced or removed within annual age groups and performance levels.
With RAEs prevalent across Italian youth Track & Field events, findings validate CAPs as a strategy to account for the influence of relative age differences on athletic performance. CAPs help establish a more equitable strategy for performance evaluation and could help improve the efficacy of long-term athlete development programming.
Journal Article