RESUMO
OBJECTIVE: To examine genomic, social, and clinical risk factors of ≥85 weight for length percentile (WFLP) at 12 months. STUDY DESIGN: Children in this study had whole-genome sequencing, and clinical and social data were collected. WFLPs at 12 months of age were grouped as follows: (1) <85th, (2) ≥85th to <95th, (3) ≥95th to <99th, and (4) ≥99th. Whole-genome sequencing data were used to analyze rare and common variants, and association of clinical and social factors was examined. RESULTS: A total of 690 children were included; WFLPs were 422 (61.2%) <85th, 112 (16.2%) ≥85th-<95th, 89 (12.9%) ≥95th-<99th, and 67 (9.7%) ≥99th. Family-related risk factors associated with greater WFLP were greater paternal body mass index, WFLP ≥99th OR 1.10 (1.03-1.16), and greater than recommended weight gain in pregnancy, WFLP ≥85th-<95th OR 1.90 (1.09-3.26). More breast milk at 6 months was protective factor: WFLP ≥85th-<95th, OR 0.98 (0.97-0.99), WFLP ≥95th-<99th OR 0.98 (0.97-0.99), and WFLP ≥99th OR 0.98 (0.96-0.99). Although none of the variants reached genome-wide significance, there was a trend toward increased prevalence of genetic variants within or near genes previously associated with obesity in children with WFLP ≥99th. CONCLUSION: This cross-sectional study identified several modifiable factors, including increased weight gain in pregnancy and decreased breast milk at 6 months, associated with greater WFLP at 12 months. Strong genetic factors were not identified.
Assuntos
Predisposição Genética para Doença , Obesidade Infantil/genética , Fatores de Risco , Alelos , Estatura , Índice de Massa Corporal , Estudos Transversais , Feminino , Frequência do Gene , Variação Genética , Humanos , Lactente , Masculino , Leite Humano , Gravidez , Controle de Qualidade , Análise de Sequência de DNA , Aumento de PesoAssuntos
Canal Anal/anormalidades , Esôfago/anormalidades , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Rim/anormalidades , Deformidades Congênitas dos Membros/diagnóstico , Deformidades Congênitas dos Membros/genética , Coluna Vertebral/anormalidades , Traqueia/anormalidades , Algoritmos , Canal Anal/patologia , Contagem de Células Sanguíneas , Diagnóstico por Imagem , Eletrocardiografia , Esôfago/patologia , Testes Genéticos , Humanos , Recém-Nascido , Rim/patologia , Exame Físico , Coluna Vertebral/patologia , Traqueia/patologiaRESUMO
We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P = 2.7 × 10(-6)), 19p12 (rs4324267, P = 1.6 × 10(-5)), 5q14.1 (rs4588572, P-value = 3.36 × 10(-5)), and 15q21.1 (rs4774497, P = 1.08 × 10(-4)). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance (P < 1 × 10(-7)). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P.