Genomic Analysis Identifies Risk Factors in Restless Legs Syndrome.

OBJECTIVE: Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. We sought to identify additional novel genetic risk factors associated with RLS susceptibility. METHODS: We performed a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in 3 population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). RESULTS: Genome-wide association analysis identified 9 independent risk loci, of which 8 had been previously reported, and 1 was a novel risk locus (LMX1B, rs35196838, OR 1.14, 95% CI 1.09-1.19, p value = 2.2 × 10-9). Furthermore, a transcriptome-wide association study also identified GLO1 and a previously unreported gene, ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg = 0.40, se = 0.08, p value = 5.4 × 10-7), depression (rg = 0.35, se = 0.06, p value = 2.17 × 10-8), and intelligence (rg = -0.20, se = 0.06, p value = 4.0 × 10-4). INTERPRETATION: Our study expands the understanding of the genetic architecture of RLS, and highlights the contributions of common variants to this prevalent neurological disorder. ANN NEUROL 2024.

Copy-number variants and polygenic risk for intelligence confer risk for autism spectrum disorder irrespective of their effects on cognitive ability.

Introduction: Rare copy number variants (CNVs) and polygenic risk for intelligence (PRS-IQ) both confer susceptibility for autism spectrum disorder (ASD) but have opposing effects on cognitive ability. The field has struggled to disentangle the effects of these two classes of genomic variants on cognitive ability from their effects on ASD susceptibility, in part because previous studies did not include controls with cognitive measures. We aim to investigate the impact of these genomic variants on ASD risk while adjusting for their known effects on cognitive ability. Methods: In a cohort of 8,426 subjects with ASD and 169,804 controls with cognitive assessments, we found that rare coding CNVs and PRS-IQ increased ASD risk, even after adjusting for their effects on cognitive ability. Results: Bottom decile PRS-IQ and CNVs both decreased cognitive ability but had opposing effects on ASD risk. Models combining both classes of variants showed that the effects of rare CNVs and PRS-IQ on ASD risk and cognitive ability were largely additive, further suggesting that susceptibility for ASD is conferred independently from its effects on cognitive ability. Despite imparting mostly additive effects on ASD risk, rare CNVs and PRS-IQ showed opposing effects on core and associated features and developmental history among subjects with ASD. Discussion: Our findings suggest that cognitive ability itself may not be the factor driving the underlying liability for ASD conferred by these two classes of genomic variants. In other words, ASD risk and cognitive ability may be two distinct manifestations of CNVs and PRS-IQ. This study also highlights the challenge of understanding how genetic risk for ASD maps onto its dimensional traits.

Genomic analysis identifies risk factors in restless legs syndrome.

Restless legs syndrome (RLS) is a neurological condition that causes uncomfortable sensations in the legs and an irresistible urge to move them, typically during periods of rest. The genetic basis and pathophysiology of RLS are incompletely understood. Here, we present a whole-genome sequencing and genome-wide association meta-analysis of RLS cases (n = 9,851) and controls (n = 38,957) in three population-based biobanks (All of Us, Canadian Longitudinal Study on Aging, and CARTaGENE). Genome-wide association analysis identified nine independent risk loci, of which eight had been previously reported, and one was a novel risk locus (LMX1B, rs35196838, OR = 1.14, 95% CI = 1.09-1.19, p-value = 2.2 × 10-9). A genome-wide, gene-based common variant analysis identified GLO1 as an additional risk gene (p-value = 8.45 × 10-7). Furthermore, a transcriptome-wide association study also identified GLO1 and a previously unreported gene, ELFN1. A genetic correlation analysis revealed significant common variant overlaps between RLS and neuroticism (rg = 0.40, se = 0.08, p-value = 5.4 × 10-7), depression (rg = 0.35, se = 0.06, p-value = 2.17 × 10-8), and intelligence (rg = -0.20, se = 0.06, p-value = 4.0 × 10-4). Our study expands the understanding of the genetic architecture of RLS and highlights the contributions of common variants to this prevalent neurological disorder.

Valor monetario de la leche materna en Bolivia / The monetary value of breast milk in Bolivia

Objetivos. Estimar el volumen de leche materna consumido por los niños bolivianos de < 36 meses de edad y el valor monetario de la sustitución de dicho volumen de leche materna con sucedáneos comerciales. Métodos. Para el análisis se tuvieron en cuenta la distribución de la población infantil por grupos de edad, la prevalencia de las diferentes prácticas de lactancia materna (exclusiva o parcial) en cada grupo de edad, el volumen promedio de leche materna consumido por los lactantes de un grupo de edad determinado y el costo de la producción y sustitución de la leche materna. Resultados. Los lactantes bolivianos consumen anualmente más de 161 millones de litros de leche materna, lo que representa un volumen promedio de 573 mL/día por cada lactante menor de un año. El valor monetario de la leche materna consumida por los lactantes bolivianos asciende a US$ 274 millones anuales. El costo promedio de sustituir la leche materna con sucedáneos comerciales en un lactante amamantado adecuadamente el primer año de vida asciende a US$ 407. Discusión. Para que la formulación y consolidación de políticas y programas de protección, promoción y apoyo a la lactancia materna sean una realidad, los líderes políticos de Bolivia han de tomar conciencia del enorme valor monetario de la leche materna

Objective. To estimate the volume of breast milk consumed by Bolivian children under 36 months of age, and the monetary value of replacing that volume of breast milk with commercial substitutes. Methods. The analysis took into account the distribution of the infant population by age groups, the prevalence of breast-feeding practices (exclusive or partial) in every age group, the average volume of breast milk consumed by the infants of a given age group, and the cost of breast milk production and replacement. Results. Bolivian infants annually consume more than 161 million liters of breast milk, which represents an average volume of 573 mL/day per infant under 1 year of age. The monetary value of breast milk consumed by the Bolivian infants amounts to US$ 274 million annually. The average cost of replacing breast milk with commercial substitutes for an infant adequately breast-fed for the first year of life would be US$ 407. Discussion. For the formulation and consolidation of policies and programs to protect, promote, and support breast-feeding to become a reality, it is necessary that the political leaders of Bolivia be aware of the enormous monetary value of breast milk