TY - JOUR
T1 - Meta-analysis of genome-wide linkage studies in BMI and obesity
AU - Saunders, Catherine L.
AU - Chiodini, Benedetta D.
AU - Sham, Pak
AU - Lewis, Cathryn M.
AU - Abkevich, Victor
AU - Adeyemo, Adebowale A.
AU - De Andrade, Mariza
AU - Arya, Rector
AU - Berenson, Gerald S.
AU - Blangero, John
AU - Boehnke, Michael
AU - Borecki, Ingrid B.
AU - Chagnon, Yvon C.
AU - Chen, Wei
AU - Comuzzie, Anthony G.
AU - Deng, Hong Wen
AU - Duggirala, Ravindranath
AU - Feitosa, Mary F.
AU - Froguel, Philippe
AU - Hanson, Robert L.
AU - Hebebrand, Johannes
AU - Huezo-Dias, Patricia
AU - Kissebah, Ahmed H.
AU - Li, Weidong
AU - Luke, Amy
AU - Martin, Lisa J.
AU - Nash, Matthew
AU - Öhman, Miina
AU - Palmer, Lyle J.
AU - Peltonen, Leena
AU - Perola, Markus
AU - Price, R. Arlen
AU - Redline, Susan
AU - Srinivasan, Sathanur R.
AU - Stern, Michael P.
AU - Stone, Steven
AU - Stringham, Heather
AU - Turner, Stephen
AU - Wijmenga, Cisca
AU - Collier, David A.
PY - 2007
Y1 - 2007
N2 - Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Results: Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Conclusion: Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.
AB - Objective: The objective was to provide an overall assessment of genetic linkage data of BMI and BMI-defined obesity using a nonparametric genome scan meta-analysis. Research Methods and Procedures: We identified 37 published studies containing data on over 31,000 individuals from more than >10,000 families and obtained genome-wide logarithm of the odds (LOD) scores, non-parametric linkage (NPL) scores, or maximum likelihood scores (MLS). BMI was analyzed in a pooled set of all studies, as a subgroup of 10 studies that used BMI-defined obesity, and for subgroups ascertained through type 2 diabetes, hypertension, or subjects of European ancestry. Results: Bins at chromosome 13q13.2- q33.1, 12q23-q24.3 achieved suggestive evidence of linkage to BMI in the pooled analysis and samples ascertained for hypertension. Nominal evidence of linkage to these regions and suggestive evidence for 11q13.3-22.3 were also observed for BMI-defined obesity. The FTO obesity gene locus at 16q12.2 also showed nominal evidence for linkage. However, overall distribution of summed rank p values <0.05 is not different from that expected by chance. The strongest evidence was obtained in the families ascertained for hypertension at 9q31.1-qter and 12p11.21-q23 (p < 0.01). Conclusion: Despite having substantial statistical power, we did not unequivocally implicate specific loci for BMI or obesity. This may be because genes influencing adiposity are of very small effect, with substantial genetic heterogeneity and variable dependence on environmental factors. However, the observation that the FTO gene maps to one of the highest ranking bins for obesity is interesting and, while not a validation of this approach, indicates that other potential loci identified in this study should be investigated further.
KW - Adiposity
KW - Diabetes
KW - Genetics
KW - Hypertension
KW - Meta-analysis
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U2 - 10.1038/oby.2007.269
DO - 10.1038/oby.2007.269
M3 - Article
C2 - 17890495
AN - SCOPUS:35548952185
SN - 1930-7381
VL - 15
SP - 2263
EP - 2275
JO - Obesity
JF - Obesity
IS - 9
ER -