Progressive influence of body mass index-associated genetic markers in rural Gambians.
BACKGROUND
In populations of European ancestry, the genetic contribution to body mass index (BMI) increases with age during childhood but then declines during adulthood, possibly due to the cumulative effects of environmental factors. How the effects of genetic factors on BMI change with age in other populations is unknown.


METHODS
In a rural Gambian population (N=2535), we used a combined allele risk score, comprising genotypes at 28 'Caucasian adult BMI-associated' single nucleotide polymorphisms (SNPs), as a marker of the genetic influence on body composition, and related this to internally-standardised z-scores for birthweight (zBW), weight-for-height (zWT-HT), weight-for-age (zWT), height-for-age (zHT), and zBMI cross-sectionally and longitudinally.


RESULTS
Cross-sectionally, the genetic score was positively associated with adult zWT (0.018±0.009 per allele, p=0.034, N=1426) and zWT-HT (0.025±0.009, p=0.006), but not with size at birth or childhood zWT-HT (0.008±0.005, p=0.11, N=2211). The effect of the genetic score on zWT-HT strengthened linearly with age from birth through to late adulthood (age interaction term: 0.0083 z-scores/allele/year; 95% CI 0.0048 to 0.0118, p=0.0000032).


CONCLUSIONS
Genetic variants for obesity in populations of European ancestry have direct relevance to bodyweight in nutritionally deprived African settings. In such settings, genetic obesity susceptibility appears to regulate change in weight status throughout the life course, which provides insight into its potential physiological role.
MRC International Nutrition Group at LSHTM, UK & MRC Unit, The Gambia; Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK.
Anthony J
AJ
Fulford
MRC Epidemiology Unit, University of Cambridge, School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Ken K
KK
Ong
MRC Epidemiology Unit, University of Cambridge, School of Clinical Medicine, Box 285 Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Cathy E
CE
Elks
MRC International Nutrition Group at LSHTM, UK & MRC Unit, The Gambia; Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK.
Andrew M
AM
Prentice
MRC International Nutrition Group at LSHTM, UK & MRC Unit, The Gambia; Department of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, Keppel Street, London, UK.
Branwen J
BJ
Hennig
D000293:Adolescent; D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005714:Gambia / Q000453:epidemiology; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012424:Rural Population; D044465:White People; D055815:Young Adult
D005819:Genetic Markers
BMI; Gambia; cross-sectional analysis; genetic risk score; longitudinal analysis