Genomewide linkage analysis of weight change in the Framingham Heart Study.
BACKGROUND
Weight gain adversely affects blood pressure, lipids, and glycemia. The genetic contribution to weight change is unknown.


METHODS
Variance components linkage analysis using microsatellites was performed on 336 families from the Framingham Heart Study offspring cohort, using a 10-cM genome-wide linkage analysis. We evaluated linkage to two traits: short-term (8-yr) weight change and long-term (up to 24-yr) weight change. Models were adjusted for age, age squared, baseline weight, smoking status, and menopausal status.


RESULTS
Mean short-term weight change ranged from 1.4-3.8 kg, and mean long-term weight change was 7.7 kg. The heritability of long-term weight change was 0.24; weight change was minimally heritable among younger individuals and over shorter follow-up intervals. We found significant evidence for linkage for long-term weight change, with a peak LOD score of 3.10 on chromosome 20 at 63.7 cM (nearest marker, D20S481). We also found suggestive evidence for linkage on chromosome 1 at 239.7 cM (LOD score, 2.28; nearest marker, D1S1644).


CONCLUSIONS
Long-term weight change is heritable, and evidence for linkage exists on chromosomes 1 and 20. Potential candidate genes include MC3R, ASIP, AGT, and HSD11B1. Additional research is necessary to uncover the genetic underpinnings of weight change that might contribute to associated adverse metabolic profiles.
Fox
Caroline S
CS
National Heart, Lung, and Blood Institute's Framingham Heart Study, 73 Mount Wayte Avenue, Suite 2, Framingham, Massachusetts 01702, USA. foxca@nhlbi.nih.gov
Heard-Costa
Nancy L
NL
Vasan
Ramachandran S
RS
Murabito
Joanne M
JM
D'Agostino
Ralph B
RB
Atwood
Larry D
LD
D000328:Adult; D001794:Blood Pressure; D001835:Body Weight / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D002890:Chromosomes, Human, Pair 20; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors