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Title: BIVARIATE LINKAGE CONFIRMS GENETIC CONTRIBUTION TO FETAL ORIGINS OF CHILDHOOD GROWTH AND CARDIOVASCULAR DISEASE RISK IN HISPANIC CHILDREN

Author
item CAI, GUOWEN - BAYLOR COLLEGE MED
item COLE, SHELLEY - SW FND FOR BIOMED RES
item HAACK, KARIN - SW FND FOR BIOMED RES
item Butte, Nancy
item COMUZZIE, ANTHONY - SW FND FOR BIOMED RES

Submitted to: Human Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/2/2007
Publication Date: 7/3/2007
Citation: Cai, G., Cole, S.A., Haack, K., Butte, N.F., Comuzzie, A.G. 2007. Bivariate linkage confirms genetic contribution to fetal origins of childhood growth and cardiovascular disease risk in Hispanic children. Human Genetics. 121(6):737-744.

Interpretive Summary: The relationship between birth weight and later risk for cardiovascular disease has been well documented in population-based studies and animal studies; however, the genetic contribution to this link has not been addressed. Recent studies have shown relationships between birth weight and later obesity and metabolic diseases; however, the genetic contribution is unknown. In this study, we explored these relationships in 1,030 Hispanic children enrolled in the Viva La Familia Study. Body weight and composition, blood pressure, fasting glucose, insulin, lipids, and liver enzymes were measured. Birth weights were obtained from Texas birth certificates. Quantitative genetic analyses were conducted using a family-based genome scan. We showed that birth weight was highly heritable, as were the metabolic risk factors. Birth weight was positively correlated to later childhood body weight, height, BMI, but not percent fat mass. Genetically, birth weight was negatively related to blood lipids. The genome scan of birth weight identified a chromosomal region at 10q22 linked significantly to birth weight. We concluded that chromosome 10q22 harbors genes that influence both birth weight and childhood body size and cardiovascular disease risk in Hispanic children. A genetic contribution to the relationship between birth weight and later risk for cardiovascular disease was confirmed in this study, which advances our understanding of factors influencing metabolic diseases.

Technical Abstract: Birth weight has been shown to be associated with obesity and metabolic diseases in adulthood; however, the genetic contribution is still controversial. The objective of this analysis is to explore the genetic contribution to the relationship between birth weight and later risk for obesity and metabolic diseases in Hispanic children. Subjects were 1,030 Hispanic children in the Viva La Familia Study. Phenotypes included body size, body composition, blood pressure, fasting glucose, insulin, lipids, and liver enzymes. Birth weights were obtained from Texas birth certificates. Quantitative genetic analyses were conducted using SOLAR software. Birth weight was highly heritable, as were all other phenotypes. Phenotypically, birth weight was positively correlated to childhood body size parameters. Decomposition of these phenotypic correlations into genetic and environmental components revealed significant genetic correlations, ranging from 0.30 to 0.59. Negative genetic correlations were seen between birth weight and lipids. The genome scan of birth weight mapped to a region near marker D10S537 (LOD = 2.6). The bivariate genome-wide scan of birth weight and childhood weight or total cholesterol improved the LOD score to 3.09 and 2.85, respectively. Chromosome 10q22 harbors genes influencing both birth weight and childhood body size and cardiovascular disease risk in Hispanic children.