New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Exterior view of Martin Goldschmidt's business; Kurfuerstendamm 34, Berlin W.15 Portraits Men

Born 1879?; Married September 2, 1903 in Leipzig to Paula Harmelin; Father of Henry H. Goldschmidt Gould and Ruth Augusta Beatrice Goldschmidt

Martin Goldschmidt reading on a park bench Portraits Men

Handwritten postcard addressed to Ruth Goldschmidt in Italy and dated 1937 from Zurich

Ruth Augusta Beatrice Goldschmidt with her parents Paula Goldschmidt née Harmelin and Martin Goldschmidt, walking on the street outside the Richmond Park Hotel; Karlsbad Portraits Family

Paula Goldschmidt, née Harmelin, born 1880; Martin Goldschmidt, born circa 1879; Ruth Augusta Beatrice Goldschmidt, born 1923?

Yasha and Riva outside their lighting store; Martin Luter Strasse, Berlin Portraits Couples

Relatives of the Judey-Barosin and Finkel families

Martin Buber with Naemah Beer-Hofmann Portraits Groups

Handwritten on verso: Prof. Martin Buber mit Naemah Beer-Hofmann in meinem Zimmer, Kurhaus Sonn-Matt bei Luzern. September 1963 fuer meine leibe Lily an einem schweren Tag, der durch sie viel leichter wurde.

Painting of Freiherr Martin von Magnus Family Portraits Family

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Martin Riesenburger portrait portraits men

Martin Riesenburger (May 14, 1896 – Apr. 14, 1966) was Prediger (Preacher) for the Jewish community in Berlin-Weissensee throughout the Nazi era (protected by his gentile wife, Natalie Riesenburger). In 1953 he became Rabbi of the Jewish community in Berlin (East) and then Landesrabbiner of the German Democratic Republic.

Wedding portrait of Martin and Lotte Lewin Portraits Couples

Handwritten thank you note under photograph signed by Lotte Lewin dated February 6, 1935

Yasha and Riva outside their lighting store; Martin Luter Strasse, Berlin Portraits Couples

Relatives of the Judey-Barosin and Finkel families

Silver locket-style photograph frame containing portraits of Martin Wasserzug and Gaby Netter (later Glueckselig) Portraits Couples

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Martin Goldschmidt taking a morning walk and eating breakfast with the "Lavanguardia" newspaper; Barcelona Portraits Men

Born 1879?; Married September 2, 1903 in Leipzig to Paula Harmelin; Father of Henry H. Goldschmidt Gould and Ruth Augusta Beatrice Goldschmidt

Martin Goldschmidt and Paula Goldschmidt née Harmelin; Leipzig Portraits Couples

Paula Goldschmidt, née Harmelin, born 1880; Martin Goldschmidt, born circa 1879; Married September 2, 1903 in Leipzig

Studio portraits of Martin Goldschmidt Portraits Men

Born 1879?; Married September 2, 1903 in Leipzig to Paula Harmelin; Father of Henry H. Goldschmidt Gould and Ruth Augusta Beatrice Goldschmidt