The Gottschalk family on the beach; Norderney, Germany.

(l-r) Elizabeth, Hans Ludwing (Hal), the maid, Ursula, Walter, Freddy, Therese (in Strandkorg) and Kurt standing

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.

Portrait of the six Baum family siblings Portraits Family

Standing are Fritz, Joseph and Lilly. The youngest is Hans. Erich is seated center and Walter is seated on the far right.

Fanny and Hugo Eichenwald with two of their three children, Fritz and Hanne outside of their home; Rheine Portraits; Family

Digital Image

Isidor Simon seated at an outdoor table with his wife Friederike nee Falkenburg and two grandchildren, Helmuth and Walther Simon Portraits Family

Digital Image

Portrait of Austrian writer Karl Kraus reading and holding a cigar; Berlin Portraits Men

Digital Image

Portrait of Paul Kraft; Stockholm Portraits Men

Digital Image

Fini Loewenthal with Justin Loewenthal in uniform; Regensburg Portraits Men

Digital Image

Hilde Loewi; Regensburg Portraits Women

Digital Image

Dina Loewenthal outdoors Portraits Women

Digital Image

Henry Rosenbaum seated at a desk smoking a cigar and sketching; New York Portraits Men

Digital Image

Engagement party for Siegfried Vogel and Gerda Goldberger Portraits Groups

Digital Image

Portrait of Erna Strobach Portraits Women

Digital Image

Portrait of Regina M. Marvin-Hausman; Manchester Portraits Women

Digital Image