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.
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.
Authors: Sungshim Lani Park; Iona Cheng; Sarah A Pendergrass; Anna M Kucharska-Newton; Unhee Lim; Jose Luis Ambite; Christian P Caberto; Kristine R Monroe; Fredrick Schumacher; Lucia A Hindorff; Matthew T Oetjens; Sarah Wilson; Robert J Goodloe; Shelly-Ann Love; Brian E Henderson; Laurence N Kolonel; Christopher A Haiman; Dana C Crawford; Kari E North; Gerardo Heiss; Marylyn D Ritchie; Lynne R Wilkens; Loïc Le Marchand Journal: Am J Epidemiol Date: 2013-07-02 Impact factor: 4.897
Authors: Brett C Haberstick; Jeffery M Lessem; Matthew B McQueen; Jason D Boardman; Christian J Hopfer; Andrew Smolen; John K Hewitt Journal: Behav Genet Date: 2010-01-20 Impact factor: 2.805
Authors: Branwen J Hennig; Anthony J Fulford; Giorgio Sirugo; Pura Rayco-Solon; Andrew T Hattersley; Timothy M Frayling; Andrew M Prentice Journal: BMC Med Genet Date: 2009-03-05 Impact factor: 2.103
Authors: Titta Salopuro; Leena Pulkkinen; Jaana Lindström; Marjukka Kolehmainen; Anna-Maija Tolppanen; Johan G Eriksson; Timo T Valle; Sirkka Aunola; Pirjo Ilanne-Parikka; Sirkka Keinänen-Kiukaanniemi; Jaakko Tuomilehto; Markku Laakso; Matti Uusitupa Journal: BMC Med Genet Date: 2009-09-21 Impact factor: 2.103